Lyme disease is a serious bacterial infection caused by a tick bite and affects humans and animals.
This page contains citations and complete abstracts for medical and scientific articles from the National Institutes of Health (NIH), National Library of Medicine (NLM) MEDLINE database about persistence or relapse of Lyme disease infection despite "appropriate" or "conventional" antibiotic treatment. Citations are sorted by date within categories with particularly significant portions highlighted in bold red lettering. Links to free online full text articles are indicated by bold lime lettering.
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Clin Rheumatol 2002 Aug;21(4):330-4
Seronegative Lyme Arthritis caused by Borrelia garinii.
Dejmkova H, Hulinska D, Tegzova D, Pavelka K, Gatterova J, Vavrik P.
Institute of Rheumatology, Prague.
A case of a female patient suffering from Lyme arthritis (LA) without elevated
antibody levels to Borrelia burgdorferi sensu lato is reported. Seronegative
Lyme arthritis was diagnosed based on the classic clinical manifestations and
DNA-detected Borrelia garinii in blood and synovial fluid of the patient, after
all other possible causes of the disease had been ruled out.
The disease was
resistant to the first treatment with antibacterial agents. Six months after the
therapy, arthritis still persisted and DNA of Borrelia garinii was repeatedly
detected in the synovial fluid and the tissue of the patient.
At the same time,
antigens or parts of spirochaetes were detected by electron microscopy in the
synovial fluid, the tissue and the blood of the patient. The patient was then
repeatedly treated by antibiotics and synovectomy has been performed.
PMID: 12189466 [PubMed - in process]
Int J Med Microbiol 2002 Jun;291 Suppl 33:125-37
Standardised in vitro susceptibility testing of Borrelia burgdorferi against
well-known and newly developed antimicrobial agents--possible implications for
new therapeutic approaches to Lyme disease.
Hunfeld KP, Kraiczy P, Kekoukh E, Schafer V, Brade V.
Institute of Medical Microbiology, University Hospital of Frankfurt, Germany.
K.Hunfeld@em.uni-frankfurt.de
Lyme disease represents a disorder of potentially chronic proportions, and
relatively little is known about the in vivo pharmacodynamic interactions of
antimicrobial agents with borreliae. So far, evidence-based drug regimens for
the effective treatment of Lyme disease have not been definitively established.
Moreover, therapeutic failures have been reported for almost every suitable
antimicrobial agent currently available. Resistance to treatment and a
protracted course of the disease, therefore, continue to pose problems for
clinicians in the management of patients suffering from chronic Lyme disease.
Further characterisation of the antibiotic susceptibility pattern and a better
understanding of the interactions of B. burgdorferi with antimicrobial agents
are urgently needed and continue to be crucial owing to considerable differences
in the experimental conditions and test methods applied. The development of
easily performed, new techniques for the sensitivity testing of B. burgdorferi
provides the opportunity to study factors affecting the bacteriostatic and
bactericidal action of recently introduced chemotherapeutic agents under more
standardised conditions. For the first time, these studies provide direct
evidence that, in addition to beta-lactams, macrolides, and tetracyclines which
are recommended for stage-dependent treatment of Lyme borreliosis, other
recently introduced substances, such as fluoroquinolones, everninomycins, and
the ketolide family of antimicrobial agents, also show enhanced in vitro
activity against borreliae. Some of these compounds, if effective in vivo as
well, may prove to be useful agents in the treatment of certain manifestations
of Lyme disease. As such, their potential role should be evaluated further by in
vivo experiments and clinical trials. Finally, these antimicrobial agents may
turn out to be very effective therapeutic alternatives on account of their oral
availability, favourable pharmacodynamic profiles, and high tissue levels in
cases where beta-lactames or tetracyclines cannot be administered without
detrimental side-effects.
PMID: 12141737
Orv Hetil 2002 May 26;143(21):1195-8
Comment in:
Orv Hetil. 2002 May 26;143(21):1223-4.
[Borrelia burgdorferi Group: in-vitro antibiotic sensitivity]
[Article in Hungarian]
Henneberg JP, Neubert U.
Department of Dermatology, Ludwig-Maximilians-University, Munchen, Germany.
Failures in the antibiotic therapy of Lyme disease have repeatedly been
demonstrated by post-treatment isolations of the infecting borreliae.
Analyses
of the antibiotic susceptibility patterns of borreliae may help to understand
the causes of such treatment failures and to develop new therapeutic regimens.
AIMS AND METHODS: The three subspecies of Borrelia burgdorferi known to be
pathogenic for humans and to differ in their virulence and organ affinity
possibly may also show divergent susceptibilities to some common antibacterial
agents. In order to get real clues for such probable differences we compared the
efficacy of six antimicrobial agents against 24 borrelial tick and skin isolates
belonging to the three subspecies of B. burgdorferi sensu lato. RESULTS: In five
comparative evaluations, some significantly different antibiotic sensitivity of
the three borrelial species was found. The Borrelia burgdorferi sensu stricto
isolates showed lower sensitivity to cephalosporin, tetracycline and
ciprofloxacin as well as a higher sensitivity to erythromycin compared to the B.
afzelii and B. garinii isolates. The B. garinii isolates proved to be more
sensitive to penicillin in comparison to the B. burgdorferi s.s. and B. afzelii
isolates. CONCLUSIONS:
In the light of these data, treatment failures may be
interpreted by serum and tissue levels of the antibiotic too low for an
effective killing of the infecting Spirochetes.
However, prolonged treatment
regimens applying higher dosages of antibiotics, in order to get complete
clearing of the infection, may be linked to aggravated side effects. PROPOSAL:
Therefore, the combination of different antiborrelial agents with synergistic
effect seems to be a meaningful alternative and should be included in future
studies in vitro as well as in vivo.
PMID: 12073540
TITLE:
Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus.
AUTHORS:
Breier F, Khanakah G, Stanek G, Kunz G, Aberer E, Schmidt B, Tappeiner G.
AUTHOR
AFFILIATION:
Department of Dermatology, Lainz Municipal Hospital, Wolkersbergenstrasse 1, A-1130 Vienna, Austria. brf@der.khl.magwien.gv.at
SOURCE:
Br J Dermatol 2001 Feb;144(2):387-92
ABSTRACT:
A 64-year-old woman presented with bullous and ulcerating lichen sclerosus et atrophicus (LSA) on the neck, trunk, genital and perigenital area and the extremities. Histology of lesional skin showed the typical manifestations of LSA; in one of the biopsies spirochaetes were detected by silver staining.
Despite treatment with four courses of ceftriaxone with or without methylprednisone for up to 20 days, progression of LSA was only stopped for a maximum of 1 year. Spirochaetes were isolated from skin cultures obtained from enlarging LSA lesions. These spirochaetes were identified as Borrelia afzelii by
sodium dodecyl sulphate--polyacrylamide gel electrophoresis and polymerase chain reaction (PCR) analyses. However, serology for B. burgdorferi sensu lato was repeatedly negative. After one further 28-day course of ceftriaxone the lesions stopped expanding and sclerosis of the skin was diminished.
At this time cultures for spirochaetes and PCR of lesional skin for B. afzelii DNA remained negative. These findings suggest a pathogenetic role for B. afzelii in the development of LSA and a beneficial effect of appropriate antibiotic treatment.
PMID: 11251580
TITLE:
Lyme arthritis in children and adolescents: outcome 12 months after initiation of antibiotic therapy.
AUTHORS:
Bentas W, Karch H, Huppertz HI.
AUTHOR
AFFILIATION:
Children's Hospital and Institute of Hygiene and Microbiology, University of Wurzburg, Germany.
SOURCE:
J Rheumatol 2000 Aug;27(8):2025-30
Comment in:
J Rheumatol. 2000 Aug;27(8):1836-8.
ABSTRACT:
OBJECTIVE:
Lyme arthritis in children and adolescents due to infection with Borrelia burgdorferi responds well to intravenous and oral antibiotics, but nonresponders have been described with all antibiotic regimens tested and a standard therapy has not yet been established. We examined causes of the failure of antibiotic treatment in the presence of persistent organisms and autoimmune mechanisms.
METHODS: A prospective multicenter study was carried out in 55 children and adolescents with Lyme arthritis. RESULTS: There were significant
differences between younger and older patients with pediatric Lyme arthritis. Younger patients were more likely to have fever at the onset of arthritis and to have acute or episodic arthritis. Older patients were more likely to have chronic arthritis, higher levels of IgG antibodies to B. burgdorferi (by ELISA and immunoblot), and a longer interval between antibiotic treatment and the disappearance of arthritis. Of 51 patients followed for at least 12 months after
initiation of antibiotic treatment, 24% retained manifestations of the disease including arthritis (8 patients) and arthralgias (4 patients). These patients were predominantly female (9/12) and were significantly older than patients without residual symptoms.
Patients who had received intraarticular steroids prior to antibiotic treatment required significantly more courses of antibiotic treatment and the time required for disappearance of the arthritis was longer.
CONCLUSION: Pediatric Lyme arthritis is more benign in younger children. Lyme
arthritis should be excluded as a possible cause of arthritis prior to the administration of intraarticular steroids.
PMID: 10955347
TITLE:
[Pars plana vitrectomy in Borrelia burgdorferi endophthalmitis]
Publisher abstract:
http://www.onjoph.com/global/klimo/english/iss213-6.html
AUTHORS:
Meier P; Blatz R; Gau M; Spencker FB; Wiedemann P
AUTHOR
AFFILIATION:
Klinik und Poliklinik fur Augenheilkunde der Universitat Leipzig.
SOURCE:
Klin Monatsbl Augenheilkd 1998 [sic - should read 1999] Dec;213(6):351-4
ABSTRACT:
BACKGROUND: Ocular manifestations of Lyme borreliose present with
unusual forms of conjunctivitis, keratitis, optic nerve disease,
uveitis, vitritis and rarely endophthalmitis. CASE REPORT: A 57-year-
old man working as logger in Sax-ony-Anhalt suffering from an
endophthalmitis on his left eye was referred to us. The vision of his
left eye was intact light perception and hand motions. The slit-lamp
examination revealed severe inflammation of the anterior chamber with
hypopyon, posterior synechiae, and opacity of the posterior lens
capsule. Funduscopy showed no red reflex, no retinal details. In the
local hospital serum analysis was performed and showed in
Western-Blot IgM- and IgG-antibodies against Borrelia burgdorferi.
Despite of intravenous application of ceftriaxon for 14 days
panuveitis persisted, and endophthalmitis developed when antibiotic
therapy was finished. RESULTS: During pars plana vitrectomy a sharply
delineated cystic lesion containing yellowish fluid was revealed, and
creamy yellow fluid was aspirated. Microscopically in
hematoxylineosin stained slides of the aspirate structures consistent
with Borrelia burgdorferi were found. Postoperatively vision
increased to 1/15.
Despite of a second intravenous ceftriaxon
treatment for 14 days we observed a retinal vasculitis in the follow
up of 6 months. CONCLUSIONS: Despite intravenous ceftriaxon-therapy
borrelia burgdorferi must have survived in the vitreous body. Further
investigations are required with respect to the use of other
antibiotics or immunosuppressives.
TITLE:
Lyme meningitis: a one-year follow up controlled study
AUTHORS:
Cimperman J; Maraspin V; Lotric-Furlan S
Ruzic-Sabljic E; Strle F
AUTHOR
AFFILIATION:
Department of Infectious Diseases, University Medical Centre,
Ljubljana, Slovenia.
SOURCE:
Wien Klin Wochenschr 1999 Dec 10;111(22-23):961-3
ABSTRACT:
Thirty-six patients with Lyme meningitis diagnosed at the Department
of Infectious Diseases, University Medical Centre, Ljubljana in 1993
and 1994 were enrolled in a prospective study. All patients had
lymphocytic meningitis, negative serum IgM antibody titres to
tick-borne encephalitis virus and met at least one of the following
four criteria: i) isolation of Borrelia burgdorferi sensu lato from
cerebrospinal fluid (2 patients), ii) intrathecal borrelial antibody
production (22 patients) iii) seroconversion to borrelial antigens (3
patients) and/or iv) erythema migrans in the period of four months
prior to the onset of neurological involvement (21 patients).
All patients underwent antibiotic treatment and were followed up for one
year. The results of our study revealed that Lyme meningitis
frequently occurs without meningeal signs and is often accompanied by
additional neurological and/or other manifestations of Lyme
borreliosis. During the first year after antibiotic treatment, minor
and major manifestations of Lyme borreliosis persisted or occurred
for the first time in several patients. They were not infrequent even
at the examination performed one year after therapy.
TITLE:
Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis
Full text article: (free registration)
Ann Med 1999; 31: 225-32
AUTHORS:
Oksi J; Marjamaki M; Nikoskelainen J; Viljanen MK
AUTHOR
AFFILIATION:
Department of Medicine, Turku University Central Hospital, Finland.
jarmo.oksi@utu.fi
SOURCE:
Ann Med 1999 Jun;31(3):225-32
ABSTRACT:
A total of 165 patients with disseminated Lyme borreliosis (diagnosed
in 1990-94, all seropositive except one culture-positive patient)
were followed after antibiotic treatment, and 32 of them were
regarded as having a clinically defined treatment failure. Of the 165
patients, 136 were tested by polymerase chain reaction (PCR) during
the follow-up. PCR was positive from the plasma of 14 patients 0-30
months after discontinuation of the treatment, and 12 of these
patients had a clinical relapse. In addition, Borrelia burgdorferi
was cultured from the blood of three patients during the follow-up.
All three patients belonged to the group with relapse, and two of
them were also PCR positive. This report focuses on the 13 patients
with clinical relapse and culture or PCR positivity. Eight of the
patients had culture or PCR- proven initial diagnosis, the diagnosis
of the remaining five patients was based on positive serology only.
All 13 patients were primarily treated for more than 3 months with
intravenous and/or oral antibiotics (11 of them received intravenous
ceftriaxone, nine for 2 weeks, one for 3 weeks and one for 7 weeks,
followed by oral antibiotics). The treatment caused only temporary
relief in the symptoms of the patients. All but one of them had
negative PCR results immediately after the first treatment. The
patients were retreated usually with intravenous ceftriaxone for 4-6
weeks. None of them was PCR positive after the retreatment. The
response to retreatment was considered good in nine patients.
We conclude that the treatment of Lyme borreliosis with appropriate
antibiotics for even more than 3 months may not always eradicate the
spirochete.
By using PCR, it is possible to avoid unnecessary
retreatment of patients with 'post-Lyme syndrome' and those with
'serological scars' remaining detectable for months or years after
infection.
TITLE:
[Comparative study of results of serological diagnosis of Lyme
borreliosis by indirect immunofluorescence and immunoenzyme analysis]
AUTHORS:
Kufko IT; Mel'nikov VG; Andreeva EA; Sokolova ZI; Lesniak OM; Beikin IaB
AUTHOR
AFFILIATION:
Klinik und Poliklinik fur Augenheilkunde der Universitat Leipzig.
SOURCE:
Klin Lab Diagn 1999 Mar;(3):34-7
ABSTRACT:
A total of 176 sera from 73 patients with verified Lyme borreliosis at
different stages of the disease are examined. Serological diagnosis
was carried out by 2 methods: indirect immunofluorescence (IIF) with
corpuscular B. burgdorferi antigen and enzyme immunoassay (EIA) with
purified flagellar B. burgdorferi antigen (Dako). EIA with Dako
antigen is more sensitive for the diagnosis of Lyme borreliosis at
any period of the disease than IIF. Analysis of correlations between
the results of IIF and EIA showed correlation in the levels of IgG
but not IgM antibodies. The findings confirmed a previous hypothesis
that inadequate antibacterial therapy before investigation decreases
the level of antibodies to Borrelia. In patients with a history of
Lyme borreliosis, antibodies to B. burgdorferi are detected less
frequently by both IIF and EIA.
Patients with persistent levels of
antibodies to B. burgdorferi, even without clinical signs of
infection, are in need of regular check-ups, because the prognostic
significance of antibodies to B. burgdorferi is unknown and relapses
may occur after months and years.
TITLE:
A proposal for the reliable culture of Borrelia burgdorferi from patients with chronic Lyme disease, even from those previously aggressively treated.
AUTHORS:
Phillips SE; Mattman LH; Hulinska D; Moayad H
AUTHOR
AFFILIATION:
Greenwich Hospital, CT 06830, USA.
SOURCE:
Infection 1998 Nov-Dec;26(6):364-7
ABSTRACT:
Since culture of Borrelia burgdorferi from patients with chronic Lyme
disease has been an extraordinarily rare event, clarification of the
nature of the illness and proving its etiology as infectious have
been difficult. A method for reliably and reproducibly culturing B.
burgdorferi from the blood of patients with chronic Lyme disease was
therefore sought by making a controlled blood culture trial studying
47 patients with chronic Lyme disease. All had relapsed after
long-term oral and intravenous antibiotics. 23 patients with other
chronic illness formed the control group. Positive cultures were
confirmed by fluorescent antibody immuno-electron microscopy using
monoclonal antibody directed against Osp A, and Osp A PCR. 43/47
patients (91%) cultured positive. 23/23 controls (100%) cultured
negative.
Although persistent infection has been, to date, strongly
suggested in chronic Lyme disease by positive PCR and antigen
capture, there are major problems with these tests. This new method
for culturing B. burgdorferi from patients with chronic Lyme disease
certainly defines the nature of the illness and establishes that it
is of chronic infectious etiology.
This discovery should help to
reestablish the gold standard in laboratory diagnosis of Lyme
disease.
TITLE:
Comparison of oral cefixime and intravenous ceftriaxone followed by oral
amoxicillin in disseminated Lyme borreliosis.
AUTHORS:
Oksi J; Nikoskelainen J; Viljanen MK
AUTHOR AFFILIATION:
Department of Medicine, Turku University Central Hospital,
Finland.
SOURCE:
Eur J Clin Microbiol Infect Dis 1998 Oct;17(10):715-9
ABSTRACT:
Two treatment regimens for disseminated Lyme borreliosis (mainly
neurologic and musculoskeletal manifestations) were compared in a
randomized trial. A group of 30 patients received oral cefixime 200
mg combined with probenecid 500 mg three times daily for 100 days.
Another group of 30 patients received intravenous ceftriaxone 2 g
daily for 14 days followed by oral amoxicillin 500 mg combined with
probenecid 500 mg three times daily for 100 days. There was no
statistically significant difference in the outcome of infection
between the two groups. However, the total number of patients with
relapses or no response at all and the number of positive polymerase
chain reaction findings after therapy were greater in the cefixime
group.
The general outcomes of infection in patients with
disseminated Lyme borreliosis after 3-4 months of therapy indicate
that prolonged courses of antibiotics may be beneficial in this
setting, since 90% of the patients showed excellent or good treatment
responses.
TITLE:
Lyme borreliosis--a review of the late stages and treatment of four
cases.
Publisher abstract:
http://allserv.rug.ac.be/~ivndorpe/ar533.htm
AUTHORS:
Petrovic M; Vogelaers D; Van Renterghem L; Carton D; De Reuck J;
Afschrift M
AUTHOR
AFFILIATION:
Department of Internal Medicine, University Hospital Ghent, Belgium.
SOURCE:
Acta Clin Belg 1998 Jun;53(3):178-83
ABSTRACT:
Difficulties in diagnosis of late stages of Lyme disease include low
sensitivity of serological testing and late inclusion of Lyme disease
in the differential diagnosis. Longer treatment modalities may have
to be considered in order to improve clinical outcome of late disease
stages. These difficulties clinical cases of Lyme borreliosis.
The different clinical cases illustrate several aspects of late
borreliosis: false negative serology due to narrow antigen
composition of the used ELISA format, the need for prolonged
antibiotic treatment in chronic or recurrent forms and typical
presentations of late Lyme disease, such as lymphocytic
meningo-encephalitis and polyradiculoneuritis.
TITLE:
Culture-positive Lyme borreliosis [see comments]
AUTHORS:
Hudson BJ; Stewart M; Lennox VA; Fukunaga M; Yabuki M; Macorison H;
Kitchener-Smith J
AUTHOR
AFFILIATION:
Microbiology Department, Royal North Shore Hospital, Sydney, NSW.
bhudson@med.usyd.edu.au
COMMENTS:
Comment in: Med J Aust 1998 May 18;168(10):479-80
SOURCE:
Med J Aust 1998 May 18;168(10):500-2
ABSTRACT:
We report a case of Lyme borreliosis. Culture of skin biopsy was
positive for Borrelia garinii, despite repeated prior treatment with
antibiotics.
The patient had travelled in Europe 17 months before the
onset of symptoms, but the clinical details indicate that the
organism could have been acquired in Australia. The results of
conventional serological and histopathological tests were negative,
despite an illness duration of at least two years.
TITLE:
Detection of Borrelia burgdorferi by polymerase chain reaction in
synovial membrane, but not in synovial fluid from patients with
persisting Lyme arthritis after antibiotic therapy.
Publisher abstract:
http://ard.bmjjournals.com/cgi/content/abstract/57/2/118
AUTHORS:
Priem S; Burmester GR; Kamradt T; Wolbart K; Rittig MG; Krause A
AUTHOR
AFFILIATION:
Charite University Hospital, Department of Medicine III, Rheumatology
and Clinical Immunology, Berlin, Germany.
SOURCE:
Ann Rheum Dis 1998 Feb;57(2):118-21
ABSTRACT:
OBJECTIVES: To identify possible sites of bacterial persistence in
patients with treatment resistant Lyme arthritis. It was determined
whether Borrelia burgdorferi DNA may be detectable by polymerase
chain reaction (PCR) in synovial membrane (SM) when PCR results from
synovial fluid (SF) had become negative after antibiotic therapy.
METHODS: Paired SF and SM specimens and urine samples from four
patients with ongoing or recurring Lyme arthritis despite previous
antibiotic therapy were investigated. A PCR for the detection of B
burgdorferi DNA was carried out using primer sets specific for the
ospA gene and a p66 gene of B burgdorferi. RESULTS: In all four
cases, PCR with either primer set was negative in SF and urine, but
was positive with at least one primer pair in the SM specimens. In
all patients arthritis completely resolved after additional
antibiotic treatment. CONCLUSIONS:
These data suggest that in
patients with treatment resistant Lyme arthritis negative PCR results
in SF after antibiotic therapy do not rule out the intraarticular
persistence of B burgdorferi DNA. Therefore, in these patients both
SF and SM should be analysed for borrelial DNA by PCR as positive
results in SM are strongly suggestive of ongoing infection.
TITLE:
Lyme borreliosis--problems of serological diagnosis.
AUTHORS:
Hofmann H
AUTHOR
AFFILIATION:
Klinik fur Dermatologie und Allergologie am Biederstein,
Technische Universitat Munchen, Germany.
SOURCE:
Infection 1996 Nov-Dec;24(6):470-2
ABSTRACT:
As long as test procedures are not standardized, the serological
results of IgM- and IgG-antibodies in Lyme borreliosis must be
interpreted with caution and always in the context of clinical signs
and symptoms. False negative results occur primarily during the first
weeks of infection. In erythema migrans of less than 4 weeks'
duration, 50% of patients are seronegative even with newly designed
ELISAs. At this early stage of the infection the therapeutic decision
has to be established on the basis of clinical criteria. Frequently
IgM- and/or IgG-antibodies develop during antibiotic therapy. After 4
weeks' duration 80% of patients have elevated borrelial antibodies
detectable with recently developed ELISAs. Positive and borderline
results should be confirmed by Western blot. False positive results,
particularly slightly elevated IgM, may occur in a variety of other
diseases.
Another problem is the persistence of Borrelia-specific IgM
antibodies after therapy.
Serological follow-up can only be carried
out with the same methods in the same laboratory.
Retreatment should
be considered if IgM antibodies are increasing significantly and new
symptoms are occurring.
TITLE:
Ultrastructural demonstration of spirochetal antigens in synovial fluid
and synovial membrane in chronic Lyme disease: possible factors
contributing to persistence of organisms.
AUTHORS:
Nanagara R; Duray PH; Schumacher HR Jr
AUTHOR
AFFILIATION:
Allergy-Immunology-Rheumatology Division, Department of
Medicine, Faculty of Medicine, KhonKaen University, Thailand.
SOURCE:
Hum Pathol 1996 Oct;27(10):1025-34
ABSTRACT:
To perform the first systematic electronmicroscopic (EM) and
immunoelectron microscopy (IEM) study of the pathological changes and
the evidence of spirochete presence in synovial membranes and
synovial fluid (SF) cells of patients with chronic Lyme arthritis. EM
examination was performed on four synovial membrane and eight SF cell
samples from eight patients with chronic Lyme disease. Spirochetal
antigens in the samples were sought by IEM using monoclonal antibody
to Borrelia burgdorferi outer surface protein A (OspA) as the
immunoprobe. Prominent ultrastructural findings were surface
fibrin-like material, thickened synovial lining cell layer and signs
of vascular injury. Borrelia-like structures were identified in all
four synovial membranes and in two of eight SF cell samples. The
presence of spirochetal antigens was confirmed by IEM in all four
samples studied (one synovial membrane and three SF cell samples).
OspA labelling was in perivascular areas, deep synovial stroma among
collagen bundles, and in vacuoles of fibroblasts in synovial
membranes; and in cytophagosomes of mononuclear cells in SF cell
samples.
Electron microscopy adds further evidence for persistence of
spirochetal antigens in the joint in chronic Lyme disease. Locations
of spirochetes or spirochetal antigens both intracellulary and
extracellulary in deep synovial connective tissue as reported here
suggest sites at which spirochaetes may elude host immune response
and antibiotic treatment.
TITLE:
Borrelia burgdorferi DNA in the urine of treated patients with chronic
Lyme disease symptoms. A PCR study of 97 cases.
AUTHORS:
Bayer ME; Zhang L; Bayer MH
AUTHOR
AFFILIATION:
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
SOURCE:
Infection 1996 Sep-Oct;24(5):347-53
ABSTRACT:
The presence of Borrelia burgdorferi DNA was established by PCR from
urine samples of 97 patients clinically diagnosed as presenting with
symptoms of chronic Lyme disease.
All patients had shown erythema
chronica migrans following a deer tick bite. Most of the patients had
been antibiotic-treated for extended periods of time.
We used three
sets of primer pairs with DNA sequences for the gene coding of outer
surface protein A (OspA) and of a genomic sequence of B. burgdorferi
to study samples of physician-referred patients from the mideastern
USA. Controls from 62 healthy volunteers of the same geographic areas
were routinely carried through the procedures in parallel with
patients' samples.
Of the 97 patients, 72 (74.2%) were found with
positive PCR and the rest with negative PCR. The 62 healthy
volunteers were PCR negative. It is proposed that a sizeable group of
patients diagnosed on clinical grounds as having chronic Lyme disease
may still excrete Borrelia DNA, and may do so in spite of intensive
antibiotic treatment.
TITLE:
Eucaryotic cells protect Borrelia burgdorferi from the action of
penicillin and ceftriaxone but not from the action of doxycycline and
erythromycin.
AUTHORS:
Brouqui P; Badiaga S; Raoult D
AUTHOR
AFFILIATION:
Unite des Rickettsies, Faculte de Medecine, Centre National de la
Recherche Scientifique, Marseille, France.
NLM PUBMED CIT. ID: 8726038
SOURCE:
Antimicrob Agents Chemother 1996 Jun;40(6):1552-4
ABSTRACT:
Despite appropriate antibiotic treatment, Lyme disease patients may
have relapses or may develop chronic manifestations.
The
intracellular location of Borrelia burgdorferi suggests that
antibiotics that penetrate cells will have greater efficiency.
Doxycycline or erythromycin was more effective than penicillin or
ceftriaxone in killing B. burgdorferi when the organism was grown in
the presence of eucaryotic cells.
TITLE:
Formation and cultivation of Borrelia burgdorferi spheroplast-L-form
variants [published erratum appears in Infection 1996 Jul-Aug;24(4):335]
AUTHORS:
Mursic VP; Wanner G; Reinhardt S; Wilske B; Busch U; Marget W
AUTHOR
AFFILIATION:
Max von Pettenkofer-Institut, Ludwig-Maximilians-Universitat Munchen,
Germany.
SOURCE:
Infection 1996 May-Jun;24(3):218-26
ABSTRACT:
As clinical persistence of Borrelia burgdorferi in patients with
active Lyme borreliosis occurs despite obviously adequate antibiotic
therapy, in vitro investigations of morphological variants and
atypical forms of B. burgdorferi were undertaken.
In an attempt to
learn more about the variation of B. burgdorferi and the role of
atypical forms in Lyme borreliosis, borreliae isolated from
antibiotically treated and untreated patients with the clinical
diagnosis of definite and probable Lyme borreliosis and from patient
specimens contaminated with bacteria were investigated. Furthermore,
the degeneration of the isolates during exposure to penicillin G in
vitro was analysed. Morphological analysis by darkfield microscopy
and scanning electron microscopy revealed diverse alterations.
Persisters isolated from a great number of patients (60-80%) after
treatment with antibiotics had an atypical form. The morphological
alterations in culture with penicillin G developed gradually and
increased with duration of incubation. Pleomorphism, the presence of
elongated forms and spherical structures, the inability of cells to
replicate, the long period of adaptation to growth in MKP-medium and
the mycoplasma-like colonies after growth in solid medium (PMR agar)
suggest that B. burgdorferi produce spheroplast- L-form variants.
With regard to the polyphasic course of Lyme borreliosis,
these forms
without cell walls can be a possible reason why Borrelia survive in
the organism for a long time (probably with all beta-lactam
antibiotics) [corrected] and the cell-wall-dependent antibody titers
disappear and emerge after reversion.
TITLE:
Azithromycin compared with amoxicillin in the treatment of erythema
migrans. A double-blind, randomized, controlled trial [see comments]
AUTHORS:
Luft BJ; Dattwyler RJ; Johnson RC; Luger SW; Bosler EM;
Rahn DW; Masters EJ; Grunwaldt E; Gadgil SD
AUTHOR
AFFILIATION:
Department of Medicine, State University of New York at Stony Brook,
NY 11794-8160 USA.
SOURCE:
Ann Intern Med 1996 May 1;124(9):785-91
ABSTRACT:
OBJECTIVE: To determine whether azithromycin or amoxicillin is more
efficacious for the treatment of erythema migrans skin lesions, which
are characteristic of Lyme disease. DESIGN: Randomized, double-blind,
double-dummy, multicenter study. Acute manifestations and sequelae
were assessed using a standardized format. Baseline clinical
characteristics and response were correlated with serologic results.
Patients were followed for 180 days. SETTING: 12 outpatient centers
in eight states. PATIENTS: 246 adult patients with erythema migrans
lesions at least 5 cm in diameter were enrolled and were stratified
by the presence of flu- like symptoms (such as fever, chills,
headache, malaise, fatigue, arthralgias, and myalgias) before
randomization. INTERVENTION: Oral treatment with either amoxicillin,
500 mg three times daily for 20 days, or azithromycin, 500 mg once
daily for 7 days. Patients who received azithromycin also received a
dummy placebo so that the dosing schedules were identical. RESULTS:
Of 217 evaluable patients, those treated with amoxicillin were
significantly more likely than those treated with azithromycin to
achieve complete resolution of disease at day 20, the end of therapy
(88% compared with 76%; P=0.024). More azithromycin recipients (16%)
than amoxicillin recipients (4%) had relapse (P=0.005). A partial
response at day 20 was highly predictive of relapse (27% of partial
responders had relapse compared with 6% of complete responders;
P<0.001). For patients treated with azithromycin, development of an
antibody response increased the possibility of achieving a complete
response (81% of seropositive patients achieved a complete response
compared with 60% of seronegative patients; P=0.043). Patients with
multiple erythema migrans lesions were more likely than patients with
single erythema migrans lesions (P<0.001) to have a positive antibody
titer at baseline (63% compared with 17% for IgM; 39% compared with
16% for IgG).
Fifty-seven percent of patients who had relapse were
seronegative at the time of relapse.
CONCLUSIONS: A 20-day course of
amoxicillin was found to be an effective regimen for erythema
migrans. Most patients were seronegative for Borrelia burgdorferi at
the time of presentation with erythema migrans (65%) and at the time
of relapse (57%).
TITLE:
Treatment failure in erythema migrans--a review.
AUTHORS:
Weber K
AUTHOR
AFFILIATION:
Dermatologische Privatpraxis, Munchen, Germany.
SOURCE:
Infection 1996 Jan-Feb;24(1):73-5
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. Roxithromycin and erythromycin are definitely or probably
ineffective. However, doxycycline, amoxicillin, cefuroxime,
ceftriaxone, azithromycin and high-dose penicillin V perform
comparably well.
TITLE:
Kill kinetics of Borrelia burgdorferi and bacterial findings in
relation to the treatment of Lyme borreliosis [published erratum
appears in Infection 1996 Mar-Apr;24(2):169]
AUTHORS:
Preac Mursic V; Marget W; Busch U; Pleterski Rigler D; Hagl S
AUTHOR
AFFILIATION:
Max v. Pettenkofer Institut, Ludwig-Maximilians-Universitat
Munchen, Germany.
SOURCE:
Infection 1996 Jan-Feb;24(1):9-16
ABSTRACT:
For a better understanding of the persistence of Borrelia burgdorferi
sensu lato (s.l.) after antibiotic therapy the kinetics of killing B.
burgdorferi s.l. under amoxicillin, doxycycline, cefotaxime,
ceftriaxone, azithromycin and penicillin G were determined. The
killing effect was investigated in MKP medium and human serum during
a 72 h exposure to antibiotics. Twenty clinical isolates were used,
including ten strains of Borrelia afzelii and ten strains of Borrelia
garinii. The results show that the kinetics of killing borreliae
differ from antibiotic to antibiotic. The killing rate of a given
antibiotic is less dependent on the concentration of the antibiotic
than on the reaction time. Furthermore, the data show that the
strains of B. afzelii and B. garinii have a different reaction to
antibiotics used in the treatment of Lyme borreliosis and that
different reactions to given antibiotics also exist within one
species. The B. garinii strains appear to be more sensitive to
antibiotics used in therapy. Furthermore,
the persistence of B.
burgdorferi s.l. and clinical recurrences in patients despite
seemingly adequate antibiotic treatment is described.
The patients
had clinical disease with or without diagnostic antibody titers to B.
burgdorferi.
TITLE:
Long-term results in patients with Lyme arthritis following treatment
with ceftriaxone.
AUTHORS:
Valesova H; Mailer J; Havlik J; Hulinska D; Hercogova J
AUTHOR
AFFILIATION:
1st Dept. of Internal Medicine, Charles University, Prague, Czech
Republic.
SOURCE:
Infection 1996 Jan-Feb;24(1):98-102
ABSTRACT:
A total of 35 patients with late stage Lyme borreliosis with
involvement of the joints was followed up until 3 years after a 14
day course of 2 g ceftriaxone once daily i.v. Diagnosis was confirmed
by indirect and direct microbiological methods as well as clinical
signs and symptoms.
Long term clinical results in 26 patients at 36
months were complete response or marked improvement in 19, relapse in
six and new manifestations in four of the cases, respectively.
Possible mechanisms for non-responding to therapy are discussed.
Therapy was well tolerated; in no case discontinuation of treatment
was necessary due to adverse drug reactions. The treatment results in
this group of 35 patients with Lyme arthritis are considered
successful. The data obtained are consistent with expectations based
on the published experiences with ceftriaxone in this indication.
"Long term clinical results in 26 patients at 36 months were complete
response or marked improvement in 19, relapse in six and new
manifestations in four of the cases, respectively."
TITLE:
Rapidly progressive frontal-type dementia associated with Lyme disease.
Publisher abstract:
http://neuro.psychiatryonline.org/cgi/content/abstract/7/3/345
AUTHORS:
Waniek C; Prohovnik I; Kaufman MA; Dwork AJ
AUTHOR
AFFILIATION:
New York State Psychiatric Institute, NY 10032, USA.
SOURCE:
J Neuropsychiatry Clin Neurosci 1995 Summer;7(3):345-7
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 must be considered even
in cases with purely psychiatric presentation, and prolonged
antibiotic therapy may be necessary.
TITLE:
Evaluation of the detection of Borrelia burgdorferi DNA in urine
samples by polymerase chain reaction.
AUTHORS:
Maiwald M; Stockinger C; Hassler D; von Knebel Doeberitz M; Sonntag HG
AUTHOR
AFFILIATION:
Hygiene Institut der Universitat, Heidelberg, Germany.
SOURCE:
Infection 1995 May-Jun;23(3):173-9
ABSTRACT:
It is difficult in some cases to identify an infection caused by
Borrelia burgdorferi and to monitor the effect of therapy.
Seropositivity will persist even after successful treatment and
therefore may suggest ongoing infection.
For direct detection of B.
burgdorferi DNA in human urine samples, the polymerase chain reaction
(PCR) was evaluated. A published primer system was selected, which
amplifies a 259 bp fragment from the gene encoding the 23S rRNA. The
lower detection limit of the primer system was 10 fg of extracted B.
burgdorferi DNA. Several methods for the pretreatment of urine
samples were tested. Of these, the Geneclean kit (Bio 101, USA)
showed the best results. A total of 114 urine samples from 74
patients belonging to three clinical groups was investigated: (i) 51
samples from 26 patients with active Lyme disease, (ii) 36 samples
from 27 patients with previous infection but no symptoms at the time
the urine was collected, and (iii) 27 samples from 21 seronegative
control patients without Lyme disease. B. burgdorferi DNA was
detected in 25 urine samples of 17 patients with active disease,
whereas 26 samples from this group of patients were negative. Only
one asymptomatic case with previous infection showed a positive
result, and the urine samples of the patients without Lyme disease
were uniformly negative. Two of four patients from whom samples
before and directly after onset of therapy were available converted
from negative to positive PCR results after initiation of therapy,
accompanied by the symptoms of a Jarisch- Herxheimer
reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
TITLE:
Lyme disease: a neuropsychiatric illness.
Publisher abstract:
http://ajp.psychiatryonline.org/cgi/content/abstract/151/11/1571
AUTHORS:
Fallon BA; Nields JA
AUTHOR
AFFILIATION:
Department of Psychiatry, College of Physicians and Surgeons,
Columbia University, New York.
SOURCE:
Am J Psychiatry 1994 Nov;151(11):1571-83
ABSTRACT:
OBJECTIVE: Lyme disease is a multisystemic illness that can affect the
central nervous system (CNS), causing neurologic and psychiatric
symptoms. The goal of this article is to familiarize psychiatrists
with this spirochetal illness. METHOD: Relevant books, articles, and
abstracts from academic conferences were perused, and additional
articles were located through computerized searches and reference
sections from published articles. RESULTS: Up to 40% of patients with
Lyme disease develop neurologic involvement of either the peripheral
or central nervous system. Dissemination to the CNS can occur within
the first few weeks after skin infection. Like syphilis, Lyme disease
may have a latency period of months to years before symptoms of late
infection emerge. Early signs include meningitis, encephalitis,
cranial neuritis, and radiculoneuropathies. Later, encephalomyelitis
and encephalopathy may occur. A broad range of psychiatric reactions
have been associated with Lyme disease including paranoia, dementia,
schizophrenia, bipolar disorder, panic attacks, major depression,
anorexia nervosa, and obsessive-compulsive disorder. Depressive
states among patients with late Lyme disease are fairly common,
ranging across studies from 26% to 66%.
The microbiology of Borrelia
burgdorferi sheds light on why Lyme disease can be relapsing and
remitting and why it can be refractory to normal immune surveillance
and standard antibiotic regimens. CONCLUSIONS:
Psychiatrists who work
in endemic areas need to include Lyme disease in the differential
diagnosis of any atypical psychiatric disorder.
Further research is
needed to identify better laboratory tests and to determine the
appropriate manner (intravenous or oral) and length (weeks or months)
of treatment among patients with neuropsychiatric involvement.
TITLE:
Lyme disease: an infectious and postinfectious syndrome.
AUTHORS:
Asch ES; Bujak DI; Weiss M; Peterson MG; Weinstein A
AUTHOR
AFFILIATION:
Department of Medicine, New York Medical College, Valhalla 10595.
SOURCE:
J Rheumatol 1994 Mar;21(3):454-61
ABSTRACT:
OBJECTIVE. To determine chronic morbidity and the variables that
influence recovery in patients who had been treated for Lyme disease.
METHODS. Retrospective evaluation of 215 patients from Westchester
County, NY, who fulfilled Centers for Disease Control case definition
for Lyme disease, were anti-Borrelia antibody positive and were
diagnosed and treated at least one year before our examination.
RESULTS. Erythema migrans had occurred in 70% of patients,
neurological involvement in 29%, objective cardiac problems in 6%,
arthralgia in 78% and arthritis in 41%. Patients were seen at a mean
of 3.2 years after initial treatment. A history of relapse with major
organ involvement had occurred in 28% and a history of reinfection in
18%. Anti-Borrelia antibodies, initially present in all patients,
were still positive in 32%. At followup, 82 (38%) patients were
asymptomatic and clinically active Lyme disease was found in 19 (9%).
Persistent symptoms of arthralgia, arthritis, cardiac or neurologic
involvement with or without fatigue were present in 114 (53%)
patients. Persistent symptoms correlated with a history of major
organ involvement or relapse but not the continued presence of
anti-Borrelial antibodies. Thirty-five of the 114 (31%) patients with
persistent symptoms had predominantly arthralgia and fatigue.
Antibiotic treatment within 4 weeks of disease onset was more likely
to result in complete recovery. Children did not significantly differ
from adults in disease manifestations or in the frequency of relapse,
reinfection or complete recovery.
CONCLUSION. Despite recognition and
treatment, Lyme disease is associated with significant infectious and
postinfectious sequelae.
TITLE:
[Lyme disease in China and its ocular manifestations]
AUTHORS:
Liu AN
AUTHOR
AFFILIATION:
Department of Ophthalmology, Chinese Navy General Hospital, Beijing.
SOURCE:
Chung Hua Yen Ko Tsa Chih 1993 Sep;29(5):271-3
ABSTRACT:
The authors report 30 chinese patients of ocular Lyme borreliosis,
which is a tick-borne spirochaetal disease involving multiple organ
systems. The ocular manifestations begin as conjunctivitis, and then
as uveitis, choroidoretinitis, keratitis and vitritis. Diagnosis is
based on case history and clinical and laboratory findings.
Early
cases may be cured by oral antibiotics while intravenous drip of
large dosage is needed for advanced cases, with a relapsing rate of
16%.
Prolonged systemic corticosteroids may predispose the patient to
antibiotic failure; however, topical corticosteroids in combination
with antibiotics may minimize ocular inflammation and complications.
TITLE:
First isolation of Borrelia burgdorferi from an iris biopsy.
AUTHORS:
Preac-Mursic V; Pfister HW; Spiegel H; Burk R; Wilske B; Reinhardt S;
Bohmer R
AUTHOR
AFFILIATION:
Max v. Pettenkofer Institut fur Hygiene u. Medizinische Mikrobiologie,
LM-Universitat Munchen, Germany.
SOURCE:
J Clin Neuroophthalmol 1993 Sep;13(3):155-61; discussion 162
ABSTRACT:
The persistence of Borrelia burgdorferi in six patients is described.
Borrelia burgdorferi has been cultivated from iris biopsy, skin
biopsy, and cerebrospinal fluid also after antibiotic therapy for
Lyme borreliosis. Lyme Serology: IgG antibodies to B. burgdorferi
were positive, IgM negative in four patients; in two patients both
IgM and IgG were negative. Antibiotic therapy may abrogate the
antibody response to the infection as shown by our results. Patients
may have subclinical or clinical disease without diagnostic antibody
titers. Persistence of B. burgdorferi cannot be excluded when the
serum is negative for antibodies against it.
TITLE:
Infectious agents in reactive arthritis.
AUTHORS:
Keat AC; Hughes R
AUTHOR
AFFILIATION:
Department of Rheumatology, Charing Cross Hospital, London, UK.
SOURCE:
Curr Opin Rheumatol 1993 Jul;5(4):414-9
ABSTRACT:
It is now clear that the deposition and persistence of bacterial
antigens in the joint are significant features of reactive arthritis.
It is possible that in some instances this represents persistence of
live bacteria, and several studies point to the potential value of
antimicrobial therapy.
Searches for bacterial DNA and RNA have
yielded conflicting data, however, so further developments in this
area will be of great importance. It is likely that bacterial
antigens interact in some way with class I major histocompatibility
complex (MHC) antigens in the pathogenesis of reactive arthritis.
However, with the increasing understanding of the structure and
function of HLA molecules, some evidence of a classic antigen-class I
MHC-CD8 T-lymphocyte interaction is now emerging. Thus far, the
mechanisms that link HLA-B27 and bacterial antigens with reactive
arthritis remain unclear.
TITLE:
Invasion of human skin fibroblasts by the Lyme
disease spirochete, Borrelia burgdorferi.
AUTHORS:
Klempner MS; Noring R; Rogers RA
AUTHOR AFFILIATION:
Division of Geographic Medicine and Infectious Diseases, New England
Medical Center, Tufts University School of Medicine, Boston,
Massachusetts 02111.
SOURCE:
J Infect Dis 1993 May;167(5):1074-81
ABSTRACT:
The ability of Borrelia burgdorferi to attach to and
invade human fibroblasts was investigated by
scanning electron and confocal microscopy. By
scanning electron microscopy, B. burgdorferi were
tightly adherent to fibroblast monolayers after 24-48
h but were eliminated from the cell surface by
treatment with ceftriaxone (1 microgram/mL) for 5
days.
Despite the absence of visible spirochetes on
the cell surface after antibiotic treatment, viable B.
burgdorferi were isolated from lysates of the
fibroblast monolayers.
B. burgdorferi were observed
in the perinuclear region within human fibroblasts by
laser scanning confocal microscopy. Intracellular
spirochetes specifically labeled with monoclonal
anti-flagellin antibody were also identified by
fluorescent laser scanning confocal microscopy.
These observations suggest that B. burgdorferi can
adhere to, penetrate, and invade human fibroblasts
in organisms that remain viable.
TITLE:
Urinary dysfunction in Lyme disease.
AUTHORS:
Chancellor MB; McGinnis DE; Shenot PJ; Kiilholma P; Hirsch IH
AUTHOR
AFFILIATION:
Department of Urology, Jefferson Medical College, Thomas Jefferson
University, Philadelphia, Pennsylvania.
SOURCE:
J Urol 1993 Jan;149(1):26-30
ABSTRACT:
Lyme disease, which is caused by the spirochete Borrelia burgdorferi,
is associated with a variety of neurological sequelae. We describe 7
patients with neuro-borreliosis who also had lower urinary tract
dysfunction. Urodynamic evaluation revealed detrusor hyperreflexia in
5 patients and detrusor areflexia in 2. Detrusor external sphincter
dyssynergia was not noted on electromyography in any patient. We
observed that the urinary tract may be involved in 2 respects in the
course of Lyme disease: 1) voiding dysfunction may be part of neuro-
borreliosis and 2) the spirochete may directly invade the urinary
tract. In 1 patient bladder infection by the Lyme spirochete was
documented on biopsy.
Neurological and urological symptoms in all
patients were slow to resolve and convalescence was protracted.
Relapses of active Lyme disease and residual neurological deficits
were common. Urologists practicing in areas endemic for Lyme disease
need to be aware of B. burgdorferi infection in the differential
diagnosis of neurogenic bladder dysfunction.
Conservative bladder
management including clean intermittent catheterization guided by
urodynamic evaluation is recommended.
TITLE:
Lyme disease: clinical features, classification, and epidemiology in
the upper midwest.
AUTHORS:
Agger W; Case KL; Bryant GL; Callister SM
AUTHOR
AFFILIATION:
Section of Infectious Disease, La Crosse Lutheran Hospital, Wisconsin.
SOURCE:
Medicine (Baltimore) 1991 Mar;70(2):83-90
ABSTRACT:
Lyme disease can be classified using the terminology of syphilis. In
this series of 95 cases from the upper midwest, early cases, defined
as an illness of less than 2 months, were more likely to have lived
in or recently visited a highly endemic area. Unlike late cases,
early cases presented entirely in the nonwinter months (p less than
.001). Early disease was further subdivided into primary and
secondary disease. Ninety percent of primary and 43% of secondary
cases had erythema migrans, while no late cases had active erythema
migrans (p less than .001). Clinical manifestations of nonspecific
inflammation, except for arthralgia, were more common in early than
late disease (p less than .01). In secondary cases, monoarticular
arthritis was slightly more common than polyarticular arthritis, with
the reverse occurring in late disease (p less than .05). Indirect
fluorescent antibody testing revealed a ratio of IgM to IgG
antibodies to be helpful in distinguishing early from late disease.
Antibacterial therapy in early, primary cases caused
Jarisch-Herxheimer reaction 7% of the time.
Despite longer and more
frequent parenteral therapy, late Lyme disease frequently required
retreatment, owing to poor clinical response (p less than .05).
TITLE:
Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis.
AUTHORS:
Pfister HW; Preac-Mursic V; Wilske B; Schielke E; Sorgel
F; Einhaupl KM
AUTHOR AFFILIATION:
Neurological Department, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.
SOURCE:
J Infect Dis 1991 Feb;163(2):311-8
ABSTRACT:
In this prospective, randomized, open trial, 33 patients with
Lyme neuroborreliosis were assigned to a 10-day treatment
with either ceftriaxone, 2 g intravenously (iv) every 24 h (n
= 17), or cefotaxime, 2 g iv every 8 h (n = 16).
Of the 33
patients, 30 were eligible for analysis of therapeutic
efficacy. Neurologic symptoms improved or even subsided
in 14 patients of the cefotaxime group and in 12 patients of
the ceftriaxone group during the treatment period.
At follow-up examinations after a mean of 8.1 months, 17 of 27
patients examined were clinically asymptomatic.
In one
patient Borrelia burgdorferi was isolated from the
cerebrospinal fluid (CSF) 7.5 months after ceftriaxone
therapy. CSF antibiotic concentrations were above the MIC
90 level for B. burgdorferi in nearly all patients examined.
Patients with Lyme neuroborreliosis may benefit from a
10-day treatment with ceftriaxone or cefotaxime.
However, as 10 patients were symptomatic at follow-up and borreliae
persisted in the CSF of one patient, a prolongation of
therapy may be necessary.
TITLE:
Clinical implications of delayed growth of the Lyme borreliosis
spirochete, Borrelia burgdorferi.
AUTHORS:
MacDonald AB; Berger BW; Schwan TG
AUTHOR
AFFILIATION:
Department of Pathology, Southampton Hospital, New York 11968.
SOURCE:
Acta Trop 1990 Dec;48(2):89-94
ABSTRACT:
Lyme borreliosis, a spirochetal infection caused by Borrelia
burgdorferi, may become clinically active after a period of latency
in the host.
Active cases of Lyme disease may show clinical relapse
following antibiotic therapy. The latency and relapse phenomena
suggest that the Lyme disease spirochete is capable of survival in
the host for prolonged periods of time. We studied 63 patients with
erythema migrans, the pathognomonic cutaneous lesion of Lyme
borreliosis, and examined in vitro cultures of biopsies from the
active edge of the erythematous patch. Sixteen biopsies yielded
spirochetes after prolonged incubations of up to 10.5 months,
suggesting that Borrelia burgdorferi may be very slow to divide in
certain situations. Some patients with Lyme borreliosis may require
more than the currently recommended two to three week course of
antibiotic therapy to eradicate strains of the spirochete which grow
slowly.
TITLE:
Chronic neurologic manifestations of Lyme disease [see comments]
AUTHORS:
Logigian EL; Kaplan RF; Steere AC
AUTHOR
AFFILIATION:
Department of Neurology, Tufts University School of Medicine,
Boston, MA 02111.
SOURCE:
N Engl J Med 1990 Nov 22;323(21):1438-44
ABSTRACT:
BACKGROUND AND METHODS. Lyme disease, caused by the tick-borne
spirochete Borrelia burgdorferi, is associated with a wide variety of
neurologic manifestations. To define further the chronic neurologic
abnormalities of Lyme disease, we studied 27 patients (age range, 25
to 72 years) with previous signs of Lyme disease, current evidence of
immunity to B. burgdorferi, and chronic neurologic symptoms with no
other identifiable cause. Eight of the patients had been followed
prospectively for 8 to 12 years after the onset of infection.
RESULTS. Of the 27 patients, 24 (89 percent) had a mild
encephalopathy that began 1 month to 14 years after the onset of the
disease and was characterized by memory loss, mood changes, or sleep
disturbance. Of the 24 patients, 14 had memory impairment on
neuropsychological tests, and 18 had increased cerebrospinal fluid
protein levels, evidence of intrathecal production of antibody to B.
burgdorferi, or both. Nineteen of the 27 patients (70 percent) had
polyneuropathy with radicular pain or distal paresthesias; all but
two of these patients also had encephalopathy. In 16 patients
electrophysiologic testing showed an axonal polyneuropathy. One
patient had leukoencephalitis with asymmetric spastic diplegia,
periventricular white-matter lesions, and intrathecal production of
antibody to B. burgdorferi. Among the 27 patients, associated
symptoms included fatigue (74 percent), headache (48 percent),
arthritis (37 percent), and hearing loss (15 percent). At the time of
examination, chronic neurologic abnormalities had been present from 3
months to 14 years, usually with little progression.
Six months after
a two-week course of intravenous ceftriaxone (2 g daily), 17 patients
(63 percent) had improvement, 6 (22 percent) had improvement but then
relapsed, and 4 (15 percent) had no change in their condition.
CONCLUSIONS. Months to years after the initial infection with B.
burgdorferi, patients with Lyme disease may have chronic
encephalopathy, polyneuropathy, or less commonly, leukoencephalitis.
These chronic neurologic abnormalities usually improve with
antibiotic therapy.
TITLE:
Survival of Borrelia burgdorferi in antibiotically treated patients
with Lyme borreliosis.
AUTHORS:
Preac-Mursic V; Weber K; Pfister HW; Wilske B; Gross B; Baumann A;
Prokop J
AUTHOR
AFFILIATION:
Neurologische Klinik Grosshadern, Munchen, FR Germany.
SOURCE:
Infection 1989 Nov-Dec;17(6):355-9
ABSTRACT:
The persistence of Borrelia burgdorferi in patients treated with
antibiotics is described. The diagnosis of Lyme disease is based on
clinical symptoms, epidemiology and specific IgG and IgM antibody
titers to B. burgdorferi in serum. Antibiotic therapy may abrogate
the antibody response to the infection as shown in our patients. B.
burgdorferi may persist as shown by positive culture in MKP-medium;
patients may have subclinical or clinical disease without diagnostic
antibody titers to B. burgdorferi.
We conclude that early stage of
the disease as well as chronic Lyme disease with persistence of B.
burgdorferi after antibiotic therapy cannot be excluded when the
serum is negative for antibodies against B. burgdorferi.
TITLE:
Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte
responses to Borrelia burgdorferi [see comments]
AUTHORS:
Dattwyler RJ; Volkman DJ; Luft BJ; Halperin JJ; Thomas J; Golightly MG
AUTHOR
AFFILIATION:
Department of Medicine, State University of New York, School of
Medicine, Stony Brook 11794-8161.
SOURCE:
N Engl J Med 1988 Dec 1;319(22):1441-6
ABSTRACT:
The diagnosis of Lyme disease often depends on the measurement of
serum antibodies to Borrelia burgdorferi, the spirochete that causes
this disorder. Although prompt treatment with antibiotics may
abrogate the antibody response to the infection, symptoms persist in
some patients.
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. Although these
patients had clinically active disease, none had diagnostic levels of
antibodies to B. burgdorferi on either a standard enzyme-linked
immunosorbent assay or immunofluorescence assay. On Western blot
analysis, the level of immunoglobulin reactivity against B.
burgdorferi in serum from these patients was no greater than that in
serum from normal controls.
The patients had a vigorous T-cell
proliferative response to whole B. burgdorferi, with a mean ( +/-
SEM) stimulation index of 17.8 +/- 3.3, similar to that (15.8 +/-
3.2) in 18 patients with chronic Lyme disease who had detectable
antibodies. The T-cell response of both groups was greater than that
of a control group of healthy subjects (3.1 +/- 0.5; P less than
0.001). We conclude that the presence of chronic Lyme disease cannot
be excluded by the absence of antibodies against B. burgdorferi and
that a specific T-cell blastogenic response to B. burgdorferi is
evidence of infection in seronegative patients with clinical
indications of chronic Lyme disease.
TITLE:
Treatment of erythema chronicum migrans of Lyme disease.
AUTHORS:
Berger BW
AUTHOR
AFFILIATION:
Department of Dermatology, New York University School of Medicine,
New York 10016.
SOURCE:
Ann N Y Acad Sci 1988;539:346-51
ABSTRACT:
Between June 1981 and July 1987 the efficacy of antibiotic treatment
of 215 patients with erythema chronicum migrans of Lyme disease was
evaluated in terms of the necessity for retreatment and the
prevention of the late manifestations of Lyme disease. The principal
antibiotics utilized to treat 161 patients through 1986 were varying
doses of tetracycline, or penicillin alone or in combination with
probenecid.
Two of 80 patients with a minor form of the illness and
17 of 81 patients with a major form of the illness required
retreatment.
There were four patients who did not respond to
retreatment with their original medication. A 15- to 30-day course of
amoxicillin (500 mg q.i.d.) and probenecid (500 mg q.i.d.) or
doxycycline (100 mg t.i.d.), and on three occasions ceftriaxone (2-4
g/day i.v.), were used to treat 54 patients in 1987. Although it is
too early to judge the efficacy of treatment in these patients,
increases in the incidence of Herxheimer reactions and drug eruptions
were observed. Strict compliance with treatment protocols and the
possibility of reactions to medications should be thoroughly
discussed with patients.
TITLE:
Treating erythema chronicum migrans of Lyme disease.
AUTHORS:
Berger BW
SOURCE:
J Am Acad Dermatol 1986 Sep;15(3):459-63
ABSTRACT:
The efficacy of antibiotic treatment of 117 patients with erythema
chronicum migrans of Lyme disease was evaluated in terms of the
necessity for retreatment and the prevention of the late
manifestations of Lyme disease. Fifty-six patients with a minor form
of the illness did not require retreatment and did not develop late
manifestations following antibiotic treatment. Three pregnant
patients were included in this group.
Fourteen of sixty-one patients
with a major form of the illness required retreatment, and five
developed posttreatment late manifestations of Lyme disease
consisting of Bell's palsy and persistent joint pain. Although the
preferred antibiotic for treating erythema chronicum migrans of Lyme
disease has not been conclusively established, tetracycline and
penicillin proved effective. The use of probenecid plus penicillin
may be of benefit to patients with the major form of the illness.
TITLE:
Clinical manifestations, pathogenesis, and effect of antibiotic
treatment on Lyme borreliosis in dogs.
AUTHORS:
Straubinger RK; Straubinger AF; Summers BA; Jacobson RH; Erb HN
AUTHOR
AFFILIATION:
James A. Baker Institute for Animal Health, Ithaca, New York,
USA. rks4@cornell.edu
SOURCE:
Wien Klin Wochenschr 1998 Dec 23;110(24):874-81
ABSTRACT:
BACKGROUND: Borrelia burgdorferi, the causative agent of Lyme disease,
infects humans and animals. In humans, the disease primarily affects
the skin, large joints, and the nervous system days to months after
infection. Data generated with appropriate animal model help to
understand the fundamental mechanisms of the disease. OBJECTIVE: 1)
More clearly define the clinical manifestation and pathogenetic
mechanisms of Lyme disease in dogs; 2) evaluate the effect of
antibiotics in dogs infected with B. burgdorferi; 3) describe the
effects of corticosteroids on dogs persistently infected with B.
burgdorferi. DESIGN: Specific-pathogen-free beagles were infected
with B. burgdorferi using ticks collected in an endemic Lyme disease
area. Clinical signs were recorded daily. Antibody titers were
measured by ELISA at two-week intervals. B. burgdorferi organisms
were detected in tissues by culture and PCR. Synovial fluids were
evaluated microscopically and with a chemotaxis cell migration assay.
Histological sections were examined for pathological lesions.
Specific cytokine up-regulation in tissues was detected by RT-PCR.
INTERVENTIONS: In three separate experiments, B. burgdorferi-infected
dogs received antibiotic treatment (amoxicillin; azithromycin;
ceftriaxone; doxycycline) for 30 consecutive days. Two subclinical
persistently infected dogs received oral prednisone for 14
consecutive days starting at day 420 post-infection. RESULTS: Dogs
developed acute arthritis in the joints closest to the tick bites
after a median incubation period of 68 days. Synovial membranes of
lame and non-lame dogs produced the chemokine IL-8 in response to B.
burgdorferi. Antibiotic treatment prevented or resolved episodes of
acute arthritis, but failed to eliminate the bacterium from infected
dogs. Corticosteroid treatment reactivated Lyme disease in
persistently infected dogs, which had not received antibiotics
previously. CONCLUSIONS:
B. burgdorferi disseminates through tissue
by migration following tick inoculation, produces episodes of acute
arthritis, and establishes persistent infection. The spirochete
survives antibiotic treatment and disease can be reactivated in
immunosuppressed animals.
TITLE:
Clinical and serologic follow-up in patients with neuroborreliosis.
Publisher abstract:
http://venus.lrponline.com/ips/Library/getfile.asp?FR=0&T=a&F=ab19981100060.html&JDir=neurology2&IDir=1998%2D51%2D5&J=81&I=20&A=59&FTF=ft19981100060.html&PDF=pdf19981100046.pdf&IT=1&APC=&Ads=0&EC=
AUTHORS:
Treib J; Fernandez A; Haass A; Grauer MT; Holzer G; Woessner R
AUTHOR
AFFILIATION:
Department of Neurology, University of the Saarland, Homburg, Germany.
SOURCE:
Neurology 1998 Nov;51(5):1489-91
ABSTRACT:
The authors performed a clinical and serologic follow-up study after
4.2 +/- 1.2 years in 44 patients with clinical signs of
neuroborreliosis and specific intrathecal antibody production.
All
patients had been treated with ceftriaxone 2 g/day for 10 days.
Although neurologic deficits decreased significantly, more than half
the patients had unspecific complaints resembling a chronic fatigue
syndrome and showed persisting positive immunoglobulin M serum titers
for Borrelia in the Western blot analysis.
TITLE:
Persistence of Borrelia burgdorferi in experimentally infected dogs
after antibiotic treatment.
Full text article (large pdf file - 1934K):
http://jcm.asm.org/cgi/reprint/35/1/111.pdf
AUTHORS:
Straubinger RK; Summers BA; Chang YF; Appel MJ
AUTHOR
AFFILIATION:
James A. Baker Institute for Animal Health, College of Veterinary
Medicine, Cornell University, Ithaca, New York 14853, USA.
rks4@cornell.edu
SOURCE:
J Clin Microbiol 1997 Jan;35(1):111-6
ABSTRACT:
In specific-pathogen-free dogs experimentally infected with Borrelia
burgdorferi by tick exposure, treatment with high doses of
amoxicillin or doxycycline for 30 days diminished but failed to
eliminate persistent infection.
Although joint disease was prevented
or cured in five of five amoxicillin- and five of six
doxycycline-treated dogs, skin punch biopsies and multiple tissues
from necropsy samples remained PCR positive and B. burgdorferi was
isolated from one amoxicillin- and two doxycycline-treated dogs
following antibiotic treatment. In contrast, B. burgdorferi was
isolated from six of six untreated infected control dogs and joint
lesions were found in four of these six dogs. Serum antibody levels
to B. burgdorferi in all dogs declined after antibiotic treatment.
Negative antibody levels were reached in four of six doxycycline- and
four of six amoxicillin-treated dogs. However, in dogs that were kept
in isolation for 6 months after antibiotic treatment was
discontinued, antibody levels began to rise again, presumably in
response to proliferation of the surviving pool of spirochetes.
Antibody levels in untreated infected control dogs remained high.
TITLE:
Cases of Lyme borreliosis resistant to conventional treatment: improved
symptoms with cephalosporin plus specific beta-lactamase inhibition.
AUTHORS:
Gasser R; Reisinger E; Eber B; Pokan R; Seinost G; Bergloff J;
Horwarth R; Sedaj B; Klein W
AUTHOR
AFFILIATION:
Department of Medicine, University of Graz, Austria.
SOURCE:
Microb Drug Resist 1995 Winter;1(4):341-4
ABSTRACT:
We present four cases of verified late Lyme borreliosis with
persistent symptoms and positive serology despite repeated courses of
high-dose intravenous penicillin G and/or cephalosporins (including
cefoperazone). The patients were now treated with cefoperazone 2 g
plus sulbactam 1 g bid iv for 14 days. At the end of treatment,
patients were symptom free and have remained so for the following 12
months. By then, IgG against Borrelia burgdorferi had decreased.
It
is concluded that the addition of beta-lactamase inhibitors to
intravenous treatment could be beneficial in Lyme disease refractory
to conventional treatment.
TITLE:
Seronegative chronic relapsing neuroborreliosis [see comments]
AUTHORS:
Lawrence C; Lipton RB; Lowy FD; Coyle PK
AUTHOR
AFFILIATION:
Department of Medicine, Albert Einstein College of Medicine,
New York, N.Y., USA.
SOURCE:
Eur Neurol 1995;35(2):113-7
ABSTRACT:
We report an unusual patient with evidence of Borrelia burgdorferi
infection who experienced repeated neurologic relapses despite
aggressive antibiotic therapy. Each course of therapy was associated
with a Jarisch-Herxheimer-like reaction. Although the patient never
had detectable free antibodies to B. burgdorferi in serum or spinal
fluid, the CSF was positive on multiple occasions for complexed
anti-B. burgdorferi antibodies, B. burgdorferi nucleic acids and free
antigen.
TITLE:
Chronic septic arthritis caused by Borrelia burgdorferi.
AUTHORS:
Battafarano DF; Combs JA; Enzenauer RJ; Fitzpatrick JE
AUTHOR
AFFILIATION:
Department of Medicine, Fitzsimons Army Medical Center,
Aurora, Colorado 80045-5001.
SOURCE:
Clin Orthop 1993 Dec;(297):238-41
ABSTRACT:
Chronic arthritis occurs in 10% of Lyme disease patients.
A patient
had chronic septic Lyme arthritis of the knee for seven years despite
multiple antibiotic trials and multiple arthroscopic and open
synovectomies. Spirochetes were documented in synovium and synovial
fluid (SF). Polymerase chain reaction (PCR) analysis of the SF was
consistent with Borrelia infection.
Persistent infection should be
excluded with silver stains and cultures in any patient with chronic
monoarticular arthritis and a history of Lyme disease.
TITLE:
Persistence of Borrelia burgdorferi in ligamentous tissue from a patient
with chronic Lyme borreliosis.
AUTHORS:
Haupl T; Hahn G; Rittig M; Krause A; Schoerner C; Schonherr U; Kalden
JR; Burmester GR
AUTHOR
AFFILIATION:
Department of Medicine III, University of Erlangen-Nuremberg, Germany.
SOURCE:
Arthritis Rheum 1993 Nov;36(11):1621-6
ABSTRACT:
OBJECTIVE. To document the persistence of Borrelia burgdorferi in
ligamentous tissue samples obtained from a woman with chronic Lyme
borreliosis.
METHODS. Spirochetes were isolated from samples of
ligamentous tissue, and the spirochetes were characterized
antigenetically and by molecular biology techniques. The ligamentous
tissue was examined by electron microscopy. Humoral and cellular
immune responses were analyzed.
RESULTS. Choroiditis was the first
recognized manifestation of Lyme disease in this patient. Despite
antibiotic therapy, there was progression to a chronic stage, with
multisystem manifestations.
The initially significant immune system
activation was followed by a loss of the specific humoral immune
response and a decrease in the cellular immune response to B
burgdorferi over the course of the disease. "Trigger finger"
developed, and a portion of the flexor retinaculum obtained at
surgery was cultured. Viable spirochetes were identified.
Ultramorphologically, the spirochetes were situated between collagen
fibers and along fibroblasts, some of which were deeply invaginated
by these organisms. The cultured bacteria were identified as B
burgdorferi by reactions with specific immune sera and monoclonal
antibodies, and by polymerase chain reaction amplification and
Southern blot hybridization techniques.
CONCLUSION. To our knowledge,
this is the first report of the isolation of B burgdorferi from
ligamentous tissue. This suggests that tendon tissues serve as a
specific site of spirochete residence in human hosts.
TITLE:
Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi,
from ceftriaxone in vitro.
AUTHORS:
Georgilis K; Peacocke M; Klempner MS
AUTHOR
AFFILIATION:
Department of Medicine, New England Medical Center, Boston,
Massachusetts.
SOURCE:
J Infect Dis 1992 Aug;166(2):440-4
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.
Since B. burgdorferi first infects skin, the possible
protective effect of skin fibroblasts from an antibiotic commonly
used to treat Lyme disease, ceftriaxone, was examined. 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, organisms did not survive. Spirochetes were
not protected from ceftriaxone by glutaraldehyde-fixed fibroblasts or
fibroblast lysate, suggesting that a living cell was required. The
ability of the organism to survive in the presence of fibroblasts was
not related to its infectivity. 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.
TITLE:
Long term treatment of chronic Lyme arthritis with benzathine
penicillin.
Publisher abstract:
http://ard.bmjjournals.com/cgi/content/abstract/51/8/1007
AUTHORS:
Cimmino MA; Accardo S
AUTHOR
AFFILIATION:
Dipartimento di Medicina Interna, Universita di Genova, Genoa, Italy.
SOURCE:
Ann Rheum Dis 1992 Aug;51(8):1007-8
ABSTRACT:
The cases are reported of two patients with chronic Lyme arthritis
resistant to the recommended antibiotic regimens who were cured by
long term treatment with benzathine penicillin. It is suggested that
the sustained therapeutic levels of penicillin were effective either
by the inhibition of germ replication or by lysis of the spirochaetes
when they were leaving their sanctuaries.
TITLE:
Molecular detection of persistent Borrelia burgdorferi in a man
with dermatomyositis.
AUTHORS:
Fraser DD; Kong LI; Miller FW
AUTHOR
AFFILIATION:
National Institute of Arthritis and Musculoskeletal and Skin
Diseases, National Institutes of Health, Bethesda, Maryland.
SOURCE:
Clin Exp Rheumatol 1992 Jul-Aug;10(4):387-90
ABSTRACT:
A 40-year-old white man with a several year history of various
immunologic disorders, including anti-Jo-1 autoantibody positive
dermatomyositis, developed clinical Lyme disease after being biten by
a tick.
The patient was treated with oral tetracycline and his
initial symptoms resolved; however, he suffered an exacerbation of
his muscle disease which was difficult to control despite cytotoxic
therapy. Antibiotic therapy was reinstituted after Borrelia
burgdorferi was detected in the patient's peripheral blood leukocytes
by the polymerase chain reaction (PCR). All serologic, T-cell
stimulation, and western blot analyses, however, were negative. The
patient's disease responded to oral ampicillin, probenecid therapy
and concurrent cytotoxic therapy.
Subsequent leukocyte PCR testing
has been negative for the causative agent of Lyme disease. This case
may provide an example of the in vivo immuno-modulatory effects of
spirochetes in human autoimmune disease. In addition, this case
emphasizes the potential clinical utility of PCR technology in
evaluating the persistent sero- negative Lyme disease which may occur
in immunocompromised individuals.
TITLE:
[Lyme Borreliosis: should we prepare for an epidemic?]
AUTHORS:
Boire G
AUTHOR
AFFILIATION:
Service de rhumatologie, Faculte de medecine, Universite de Sherbrooke.
SOURCE:
Union Med Can 1991 May-Jun;120(3):226-32
ABSTRACT:
Lyme Borreliosis results from the persistent infection with a
spirochete, Borrelia burgdorferi, transmitted by ticks of the Ixodes
ricinus complex. The geographic distribution of these ticks depends
on specific climatic and ecologic conditions. Lyme borreliosis is a
disease with protean manifestations whose distribution is world-wide.
In North America, the disease usually begins between May and August
with a characteristic rash, erythema chronicum migrans, accompanied
by non specific or meningitis-like symptoms. Weeks or months after
the rash, the patient may develop transient cardiac, neurologic or
musculo- skeletal manifestations, and usually more than a year later,
some patients have chronic skin, joint, or neurologic manifestations.
Antibody titers rise after four to eight weeks in most patients that
did not receive antibiotics, and serologic testing then represents
the most useful aid in diagnosis. Due to large numbers of false
positives, serologic testing should be limited to those patients with
strong clinical or epidemiological evidence of the disease.
Treatment
with appropriate antibiotics, and for adequate time, is usually
curative but in later stages patients may need to be retreated and
some may not respond.
TITLE:
Borrelia burgdorferi infection of the brain: characterization of the
organism and response to antibiotics and immune sera in the mouse model
[see comments]
AUTHORS:
Pachner AR; Itano A
AUTHOR
AFFILIATION:
Department of Neurology, Georgetown University Hospital,
Washington, DC 20007.
SOURCE:
Neurology 1990 Oct;40(10):1535-40
ABSTRACT:
To learn more about the neurologic involvement in Lyme disease, we
inoculated inbred mice with the causative agent of Lyme disease,
Borrelia burgdorferi. We cultured brains and other organs, and
measured anti-B burgdorferi antibody titers. We further studied a
brain isolate for its plasmid DNA content and its response in vitro
to immune sera and antibiotics. One strain of B burgdorferi, N40, was
consistently infective for mice, and resulted in chronic infection of
the bladder and spleen. SJL mice developed fewer culture-positive
organs and had lower antibody titers than Balb/c and C57Bl/6 mice.
Organism was cultured from the brain early in the course of
infection, and this isolate, named N40Br, was further studied in
vitro. The plasmid content of N40Br was different from that of the
infecting strain, implying either a highly selective process during
infection or DNA rearrangement in the organism in vivo. N40Br was
very sensitive to antibiotics, but only after prolonged incubation.
Immune sera from both mice and humans infected with B burgdorferi
were unable to completely kill the organism by complement-mediated
cytotoxicity.
These data demonstrate that B burgdorferi infects the
brain of experimental animals, and is resistant to immune sera in
vitro but sensitive to prolonged treatment with antibiotics.
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