Persistence or Relapse of Lyme Disease
despite "appropriate" or "conventional" antibiotic therapy

A Bibliography with Highlighted Full Abstracts

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.

Click on link shown after "TITLE:" to see complete citation/abstract.

Table of Contents

Primary references for persistent or relapse of Lyme disease

Other references - animal studies, single patient reports, etc.

Also see:

Reasons for the survival of Lyme disease bacteria (cystic forms, blebs, L-forms, etc.)
http://www.reocities.com/HotSprings/Oasis/6455/persistence-reasons.html  alt


For more information about Lyme disease



Persistence or Relapse of Lyme Disease

Note: Most of the citations or abstracts in this section were gleaned from articles found by the following three MEDLINE "search" links:

MEDLINE - persist*, etc. AND antibiotics AND Lyme disease - 390 on 5 Oct 02
MEDLINE - refractory, etc. AND Lyme disease - 113 on 5 Oct 02
MEDLINE - long-term antibiotics AND Lyme disease - 51 on 5 Oct 02

Primary references:

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.



Other references - animal studies, single patient reports, etc.:

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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Also see:

Persistence or Relapse of Lyme Disease despite "appropriate" or "conventional" antibiotic therapy
http://www.reocities.com/HotSprings/Oasis/6455/persistence-links.html  alt

See related annotated bibliographies at:

Long-Term or Repeated Antibiotic Therapy for Lyme Disease -
A Bibliography with Highlighted Full Abstracts
http://www.reocities.com/HotSprings/Oasis/6455/therapy-special-abstracts.html  alt

Long-Term or Repeated Antibiotic Therapy for Lyme Disease
http://www.reocities.com/HotSprings/Oasis/6455/long-term-treatment.html  alt

Seronegative or False Negative Lyme disease
http://www.reocities.com/HotSprings/Oasis/6455/seronegative-special.html  alt

Latent, dormant, subclinical, or asymptomatic Lyme Disease
http://www.reocities.com/HotSprings/Oasis/6455/latent-biblio.html  alt



For more information about Lyme disease, see:

Lots Of Links On Lyme Disease
http://www.reocities.com/HotSprings/Oasis/6455/lyme-links.html  alt

This document can be found at:

Persistence or Relapse of Lyme Disease - A Bibliography with Highlighted Full Abstracts
http://www.reocities.com/HotSprings/Oasis/6455/persistence-special-abstracts.html  alt

Comments or questions concerning this page should be directed to Art Doherty.

Last updated on 5 October 2002 by
Art Doherty
Lompoc, California
doherty@utech.net