F. Strle

Comparison of erythema migrans caused by Borrelia afzelii and Borrelia garinii.

Abstract.Background:We compared epidemiological and clinical characteristicsnof patients with erythema migrans (EM) caused bynBorrelia afzelii andnBorrelia garinii.Patients and Methods:200 consecutive adult patients withnB. afzelii isolated from thenskin lesion and 53 consecutive adult patients with EM caused bynB. garinii qualified for thenpresent study.Results:Comparison of the two groups revealed severalndistinctions. Patients with EM caused by B. garinii were older, had their skinnlesions more often located on the trunk but less often onnextremities, had shorter incubation and faster evolution of EM,nmore often reported associated local and certain systemicnsymptoms, had abnormal liver function test results more oftennand were more frequently seropositive.Conclusion:Early localized Lyme borreliosis caused bynB. afzelii andnB. garinii has distinctnepidemiological and clinical characteristics. Clinical featuresnof EM depend upon the genospecies of Borrelia burgdorferi sensu lato causingnthe illness.

In Vitro Susceptibility Testing of Borrelia burgdorferi Sensu Lato Isolates Cultured from Patients with Erythema Migrans before and after Antimicrobial Chemotherapy

ABSTRACT Clinical treatment failures have been reported to occur in early Lyme borreliosis (LB) for many suitable antimicrobial agents. Investigations of possible resistance mechanisms of the Borrelia burgdorferi complex must analyze clinical isolates obtained from LB patients, despite their receiving antibiotic treatment. Here, borrelial isolates obtained from five patients with erythema migrans (EM) before the start of antibiotic therapy and again after the conclusion of treatment were investigated. The 10 isolates were characterized by restriction fragment length polymorphism analysis and plasmid profile analysis and subjected to susceptibility testing against a variety of antimicrobial agents including those used for initial chemotherapy. Four out of five patients were infected by the same genospecies (Borrelia afzelii, n = 3; Borrelia garinii, n = 1) at the site of the EM lesion before and after antimicrobial therapy. In one patient the genospecies of the initial isolate (B. afzelii) differed from that of the follow-up isolate (B. garinii). No significant changes in the in vitro susceptibilities became obvious for corresponding clinical isolates before the start and after the conclusion of antimicrobial therapy. This holds true for the antimicrobial agents used for specific chemotherapy of the patients, as well as for any of the additional agents tested in vitro. Our study substantiates borrelial persistence in some EM patients at the site of the infectious lesion despite antibiotic treatment over a reasonable time period. Borrelial persistence, however, was not caused by increasing MICs or minimal borreliacidal concentrations in these isolates. Therefore, resistance mechanisms other than acquired resistance to antimicrobial agents should be considered in patients with LB resistant to treatment.

Isolation of Borrelia burgdorferi Sensu Lato from Blood of Patients with Erythema Migrans

AbstractBackground: We assessed the isolation rate of Borrelia burgdorferi sensu lato from blood in European patients with typical erythema migrans and evaluated the course and outcome of their illness.nPatients and Methods: Adult patients diagnosed with erythema migrans and from whom borreliae cultured from blood were included in this study.nResults: Borreliae were isolated from the blood of 35/2,828 (1.2%) patients, on average 7 days (range 1–47 days) after the appearance of erythema migrans. Only seven (20%) patients reported constitutional symptoms. 24/35 isolates were typed of which 20 were Borrelia afzelii and four were Borrelia garinii. 31 (88.6%) patients were treated with oral antibiotics while four (11.4%) received ceftriaxone iv. The course and outcome of the illness were favorable in all patients.nConclusion: In European patients with erythema migrans the yield of blood culturing was low, spirochetemia was often clinically silent and the course and outcome of the illness were favorable; the predominantly isolated strain was B. afzelii.

Treatment of borrelial lymphocytoma

SummaryTreatment results in 65 patients with borrelial lymphocytoma (22 on the ear lobe and 43 on the breast), registered at the Department of Infectious Diseases, University Medical Centre Ljubljana, from January 1986 to March 1995, are presented. When lymphocytoma was the sole manifestation of Lyme borreliosis or associated with erythema migrans only patients were treated orally with doxycycline, phenoxymethylpenicillin or amoxicillin for 14 days, or azithromycin for 5 days (15, 19, six and 12 patients, respectively). When signs and symptoms of disseminated borrelial infection were present (seven patients) or clinically suspected (six patients) patients received ceftriaxone or penicillin G i.v. for 14 days. Lymphocytoma disappeared within a few weeks after the institution of treatment. The speed of regression depended on the duration of lymphocytoma before the institution of therapy. The number of patients was too low and pretreatment characteristics were too heterogeneous to enable a reliable comparison of the efficacy of different antibiotics. It appears that the effectiveness of doxycycline and azithromycin is comparable and that amoxicillin performs well, but some findings may indicate that phenoxymethylpenicillin is less effective than some newer antibiotics. The optimal agent, dosage and duration of therapy for borrelial lymphocytoma have not been determined.ZusammenfassungDie Behandlungsergebnisse von 65 Patienten mit Borrelien-Lymphozytom (22 am Ohr und 43 an der Brust), die in der Abteilung für Infektionskrankheiten der Universitätsklinik Ljubljana von Januar 1986 bis März 1995 registriert wurden, werden mitgeteilt. Wenn das Lymphozytom die einzige Manifestation der Lyme-Borreliose war oder mit einem Erythema migrans einherging, wurden die Patienten 14 Tage lang oral mit Doxycyclin, Phenoxymethylpenicillin oder Amoxicillin oder 5 Tage lang mit Azithromycin behandelt (15, 19, sechs und 12 Patienten in den entsprechenden Gruppen). Wenn die Zeichen einer generalisierten Borrelieninfektion vorhanden waren (sieben Patienten) oder ein entsprechender Verdacht bestand (sechs Patienten), wurden die Patienten 14 Tage lang mit Ceftriaxon oder Penicillin G i.v. behandelt. Das Lymphozytom verschwand innerhalb weniger Wochen nach Therapiebeginn. Die Geschwindigkeit der Rückbildung war davon bestimmt, wie lange das Lymphozytom vor Therapiebeginn schon bestanden hatte. Für einen zuverlässigen Vergleich der Wirksamkeit der verschiedenen Antibiotika-Therapien waren die Anzahl der Patienten zu klein und die prätherapeutischen Daten zu heterogen. Die Wirksamkeit von Doxycyclin und Azithromycin scheint vergleichbar gut zu sein; Amoxicillin ist offensichtlich ebenfalls wirksam. Einige Daten weisen darauf hin, daß Phenoxymethylpenicillin möglicherweise weniger wirksam ist als einige der neueren Antibiotika. Das optimale Antibiotikum, Dosierung und Behandlungsdauer des Borrelien-Lymphozytoms konnten noch nicht festgelegt werden.

Concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi sensu lato in patients with acute meningitis or meningoencephalitis

SummaryFrom September 1992 to August 1993, 338 patients over the age of 15 years presented to the Department of Infectious Diseases, University Medical Centre Ljubljana, with acute lymphocytic meningitis. In 89 of these patients (26.3%) serum IgM and IgG antibodies against tick-borne encephalitis (TBE) virus were detected, and in 59 patients (17.5%) a borrelial etiology of disease was demonstrated by one or more of the following: presence of intrathecal antibody production, seroconversion to borrelial antigens, presence of erythema migrans, and/or isolation ofBorrelia burgdorferi sensu lato from skin or cerebrospinal fluid. Of the 148 patients who fulfilled criteria for TBE or borrelial infection, concomitant infection with TBE virus andB. burgdorferi sensu lato was demonstrated in 12 patients (3.6% of all patients presenting with acute lymphocytic meningitis). In the majority of patients with concomitant infection the clinical features at presentation were characteristic of, or consistent with, TBE. In addition, during follow-up studies, eight of the 12 patients subsequently developed signs and symptoms compatible with minor and/or major manifestations of Lyme borreliosis. Six patients were diagnosed with neuroborreliosis based on signs or symptoms and/or laboratory tests. These findings show that in patients with acute lymphocytic meningitis or meningoencephalitis, originating in TBE and Lyme borreliosis endemic regions, the possibility of concomitant infection should be considered.

Isolation of Borrelia burgdorferi sensu lato from blood of adult patients with borrelial lymphocytoma, Lyme neuroborreliosis, Lyme arthritis and acrodermatitis chronica atrophicans

BackgroundReports on patients with European Lyme borreliosis in whom borreliae were isolated from the blood are rare and nearly exclusively limited to those with solitary or multiple erythema migrans. Here we report on patients with other manifestations of Lyme borreliosis in whom borreliae were isolated from their blood.Patients and methodsThis is a retrospective review of the medical files of patients diagnosed with borrelial lymphocytoma, Lyme neuroborreliosis, Lyme arthritis and acrodermatitis chronica atrophicans at the Department of Infectious Diseases of the UMC Ljubljana, Slovenia, for whom a borrelia blood culture was ordered. The clinical features of patients whose blood culture tested positive for Borrelia burgdorferi sensu lato were reviewed, and the association between the proportion of patients with a positive blood culture and various clinical manifestations was examined.ResultsBorrelia burgdorferi sensu lato was isolated from the blood of 1/53 (1.9%) patients with borrelial lymphocytoma, 6/176 (3.4%) patients with Lyme neuroborreliosis, 1/13 (7.7%) patients with Lyme arthritis, and 3/200 (1.5%) patients with acrodermatitis chronica atrophicans. The time interval from the onset of symptoms attributed to Lyme borreliosis and the blood culture ranged from 1xa0day to >2xa0years (median 3.5xa0weeks). At the time of the blood culture, erythema migrans was present in 4/11 (36.4%) borrelia blood culture-positive patients, i.e. in the patient with borrelial lymphocytoma, the patient with Lyme arthritis and the 2/6 patients with Lyme neuroborreliosis. Only two of these 11 (18.2%) patients had fever at the time of the blood culture.ConclusionsIn European patients with Lyme borreliosis, borreliae can be cultured from the blood not only early in the course of the disease but also occasionally later during disease progression.

Solitary and multiple erythema migrans in children: Comparison of demographic, clinical and laboratory findings

Abstract.Background:Data on European children with erythema migrans (EM) arenlimited.Patients and Methods:553 patients, 333 with solitary and 220 with multiple EM,ndiagnosed between 1996 and 2000, were included in thenprospective study. Demographic, clinical and laboratory datanincluding borrelial serum immunofluorescence assay antibodyntiters and Borrelianburgdorferi sensu lato blood culture results werenobtained; findings in solitary and multiple EM werencompared.Results:Comparison revealed that children with multiple EM werenyounger (4.5 vs 6.5 years; p = 0.0000), less often reported antick bite at the site of later skin lesion (25% vs 46%; p =n0.0000), had a longer incubation period (22 vs 13 days; p =n0.0028), more frequently presented with a ringlike lesion (99%nvs 86%; p = 0.0000), less often reported associated local (15%nvs 41%; p = 0.0000) but not systemic symptoms (28% vs 26%, p =n0.6913), more frequently had abnormal findings on physicalnexamination (35% vs 26%; p = 0.0264), and a higher frequency ofnlaboratory abnormalities including the presence of borrelialnserum antibodies as well as B.nburgdorferi sensu lato isolated from blood (12% vsn6%; p = 0.0267); younger age and male sex were identified asnrisk factors for the isolation of Borrelia. 40/44 isolates werenBorrelia afzelii.Conclusion:Analysis of a large group of European children withnsolitary and multiple EM revealed several demographic, clinicalnand laboratory differences between the two groups.

There is inadequate evidence to support the division of the genus Borrelia

There are surely scientific, genetic or ecological arguments which show that differences exist between the relapsing fever (RF) spirochaetes and the Lyme borreliosis (LB) group of spirochaetes, both of which belong to the genus Borrelia. In a recent publication, Adeolu and Gupta [1] proposed dividing the genus Borrelia into two genera on the basis of genetic differences revealed by comparative genomics. The new genus name for the LB group of spirochaetes, Borreliella, has subsequently been entered in the GenBank database for some species of the group and in a validation list (List of new names and new combinations previously effectively, but not validly, published) [2]. However, rapidly expanding scientific knowledge and considerable conflicting evidence combined with the adverse consequences of splitting the genus Borrelia make such a drastic step somewhat premature. In our opinion, the basis of this division rests on preliminary evidence and should be rescinded for the following reasons:

Ehrlichia antibodies, leukopenia and thrombocytopenia in initial phase of tick-borne encephalitis

It is ~,ell known that Lrodes ;tcintLs ticks transmit agents of several infectious diseases including tick-borne encephalitis (TBE) virus. Borrelia burgdorferz sensu lato, rickettsiae and babesiae [l. 2], In addition, it has been recognized for several years that infections by the latter two agents cause diseases often accompanied by leukopenia and/or thrombocytopenia [21, and that early in the course of TBE leukopenia is a characteristm finding Ill. r B E and Lyme bol-reliosis are endemic in Slovenia [3]. but there has been no report on human babesiosis or rickettsiosis contracted in Slovenia. In [995, we reported that in the initial phase of TBE, in addition to the well-known leukopenia, thrombocytopema is a common finding [4, 5 t At the time of the submission of our report to this journal [5], the first descriptions of human granulocytic ehrlichiosis (HGE) began to appear in the USA [6, 7]. Recently. a case of acute H G E was also reported from Slovenia [81. Thus, it has been known since 1996 that both TBE and HGE are present in the same region of central Slovenia. It is of interest that both diseases have a remarkably simdar clinical presentation: they both develop after a tick bite and are characterized by fever and headache, and the principal laboratory abnormalit ies in both are leukopenia and thrombocytopenia. Because thrombocytopenia in the initial phase of TBE is a recent and rather unexpected finding in a disease which has existed and been studied in several European countries for over 50 years, it deserves particular mention. We have therefore raised the hypothesis that coinfection with I IGE agent or Ehrlictua chaffeensis may have contr ibuted to at least some of the findings in our patients with imtial-phase TB E infection. We present the results of our evaluation of this assumption below. Sera of 12 out of 20 (60 %) patients with TBE as described in a previous study [5]. and in whom leukopenia and/or thrombocytopenia were found during the initial phase of TBE. were available for an additional serological analysis. Acute and convalescent (6-8 weeks after first visit) sera were tested by indirect immunofluorescence antibody assay for the presence of antibodies against human granulocytic Ehrlichia (using strain USG3, propagated in HL60 promyelocyte cells) and E. chaffeensis (using commercially available antigen. MRL Diagnostics, Cypress, USA) as previously described [9]. No antibodies against H G E agent or against E. chaffeensis could be demonstra ted in any of the 12 patients sera tested. We conclude that in patients with initial-phase of TBE presenting with febrile illness, leukopenia and/or thrombocytopenia after a tick bite, no evidence for coinfection with H G E agent or with E. chaffeensis was established. Thus. the hypothesis that coinfection with H G E agent or E. chaffeensis may contribute to some findings of the initial phase of TBE has not been confirmed. This further strengthens our previous observation [5] that thrombocytopcnia and leukopenia are the result of infection with TBE virus. S. Lotri~-Furlan, M. Petrovec, 7-. Av~id-Zl~panc, l;i Str/e R e f e r e n c e s

Corrigendum: There is inadequate evidence to support the division of the genus Borrelia

Author affiliations: National Reference Centre for Borrelia, Bavarian Health and Food Safety Authority, Veterin€ arstr. 2, 85764 Oberschleißheim, Germany; European Programme for Public Health Microbiology Training, European Centre of Disease Prevention and Control (ECDC), Stockholm, Sweden; School of Health Sport and Bioscience, University of East London, Water Lane, London, UK; Department of Zoology, Slovak Academy of Sciences, Bratislava, Slovakia; Department of Ecology, Evolution and Environmental Biology, Columbia University, 1200 Amsterdam Avenue, New York, NY 10027, USA; SmartGene Services SARL, Innovation Park, Building C, EPFL-Ecublens, CH-1015 Lausanne, Switzerland; Yale School of Public Health, Laboratory of Epidemiology and Public Health, 60 College Street, New Haven, CT 06510, USA; Emeritus Professor of Animal Parasitology, University College Dublin, Dublin, Ireland; Members of the Steering Committee of the ESCMID Study Group for Borrelia (ESGBOR); Zentralinstitut für Labormedizin, Mikrobiologie and Krankenhaushygiene, Krankenhaus Nordwest, Akademisches Lehrkrankenhaus der Johann Wolfgang GoetheUniversit€ at, Steinbacher Hohl 2-26, D-60488 Frankfurt am Main, Frankfurt, Germany; Laboratoire de Bact eriologie, CNR des Borrelia, Plateau Technique de Microbiologie, Hôpitaux Universitaires de Strasbourg et Facult e de M edecine de Strasbourg, 1 rue Koeberl e, Strasbourg 67000, France; tick-radar GmbH, Haderslebener Str. 9, Berlin 12163, Germany; Molecular Genetics Lab (www.dnk-ural.ru) Biology Department, Ural Federal University named after the first President of Russia B.N.Yeltsin, Lenin Avenue, Yekaterinburg 620000, Russia; Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Paul-Ehrlich-Str, Frankfurt/Main 40, 60596, Germany; Environmental Science, Policy and Management, University of California Berkeley, 130 Mulford Hall, Berkeley CA 94720, California, USA; Borrelia Laboratory for the National Reference Centre of Tick Diseases (CNRT/ NRZK), ADMed Microbiology, La Chaux-de-Fonds 2303, Switzerland; Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Director, Public Health Risk Sciences Division, National Microbiology Laboratory, @ Saint-Hyacinthe and Guelph, Public Health Agency of Canada, Saint-Hyacinthe, Canada; Clinical and Experimental Infectious Medicine Section, Department of Clinical Sciences, Lund University, Sweden; Klinikum Dachau, Abt. Neurology u. Schlafmedizinisches Zentrum, Krankenhausstr. 15, 8521 Dachau, Germany; Department of Microbiology and Immunology, School of Medicine, New York Medical College, Basic Sciences Building, Valhalla, NY 10595, USA; Chair Bacteriology and Mykology, Department of Veterinary Science, Veterinary Faculty, LMU Munich, Veterin€ arstraße, München 13, 80539, Gemany; Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia; Universit e de Neuchâtel, Institut de Biologie, Laboratoire d’Ecologie et Evolution des Parasites, Rue Emile-Argand 11, CH-2000, Neuchâtel, Switzerland; Fondazione Edmund Mach, Research and Innovation Centre, Via Mach, 1, San Michele all’Adige, Trento, Italy; Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, MS421 Chandler Medical Center, Lexington, Kentucky, 40536-0298, USA. *Correspondence: G. Margos, Gabriele.margos@lgl.bayern.de CORRIGENDUM