Oberschleißheim, Germany
Oberschleißheim, Germany

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Stanek G.,Medical University of Vienna | Fingerle V.,National Reference Center for Borrelia | Hunfeld K.-P.,Goethe University Frankfurt | Jaulhac B.,University of Strasbourg | And 7 more authors.
Clinical Microbiology and Infection | Year: 2011

Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations. © 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases.


PubMed | Leibniz Institute for Natural Product Research and Infection Biology, University Hospital of Frankfurt, National Reference Center for Borrelia, Goethe University Frankfurt and University of Heidelberg
Type: Journal Article | Journal: Molecular microbiology | Year: 2016

Borrelia (B.) bavariensis exhibits a marked tropism for nervous tissues and frequently causes neurological manifestations in humans. The molecular mechanism by which B.bavariensis overcomes innate immunity, in particular, complement remains elusive. In contrast to other serum-resistant spirochetes, none of the B.bavariensis isolates investigated bound complement regulators of the alternative (AP) and classical pathway (CP) or proteolytically inactivated complement components. Focusing on outer surface proteins BGA66 and BGA71, we demonstrated that both molecules either inhibit AP, CP and terminal pathway (TP) activation, or block activation of the CP and TP respectively. Both molecules bind complement components C7, C8 and C9, and thereby prevent assembly of the terminal complement complex. This inhibitory activity was confirmed by the introduction of the BGA66 and BGA71 encoding genes into a serum-sensitive B.garinii strain. Transformed spirochetes producing either BGA66 or BGA71 overcome complement-mediated killing, thus indicating that both proteins independently facilitate serum resistance of B.bavariensis. The generation of C-terminally truncated proteins as well as a chimeric BGA71 protein lead to the localization of the complement-interacting binding site within the N-terminus. Collectively, our data reveal a novel immune evasion strategy of B.bavariensis that is directed against the activation of the TP.


PubMed | Global Health and Tropical Medicine GHTM, National Reference Center for Borrelia and New University of Lisbon
Type: | Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases | Year: 2016

In the last decades, several studies have reported pathogenic species of Borrelia related to those that cause Tick-borne Relapsing Fever (RF), but unexpectedly suggesting their transmission by hard ticks, known vectors of Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species, rather than by soft ticks. This study was designed to update the presence of B. burgdorferi s.l. species in ticks from several districts of mainland Portugal, where Ixodes ricinus had been previously described. Ticks (a total of 2915 specimens) were collected in seven districts throughout the country, and analyzed using molecular methods. Three nested-PCR protocols, targeting the flagellin gene (flaB), the intergenic spacer region (IGS) located between 5S and 23S rRNA, and the glpQ gene, and a conventional PCR targeting the 16S rRNA, were used for Borrelia DNA detection. Borrelia DNA was detected in 3% of the ticks from Braga, Vila Real, Lisboa, Setbal, vora and Faro districts. The obtained amplicons were sequenced and analyzed by BLASTn, and 15/63 (24%) matched with homologous sequences from Borrelia lusitaniae and 15/63 (24%) with B. garinii, being these the most prevalent species. DNA from B. burgdorferi sensu stricto (s.s.), B. valaisiana and B. afzelii were detected in 7/63 (11%), 6/63 (10%), and 2/63 (3%) of the specimens, respectively. Unexpectedly, DNA sequence (flaB) analysis from eight (13%) samples, two from Rhipicephalus sanguineus and six from Haemaphysalis punctata tick species, revealed high homology with RF-like Borrelia. Phylogenetic analyses obtained from three genetic markers (16S rRNA, flaB, and glpQ) confirmed their congruent inclusion in a strongly supported RF cluster, where they segregated in two subgroups which differ from the other Relapsing Fever species. Therefore, the results confirm the circulation of multiple species of B. burgdorferi s.l. over a wide geographic range, covering most of the Portuguese mainland territory. Surprisingly, the obtained data also revealed two putative Relapsing Fever-like Borrelia species in different species of hard ticks, possibly disclosing the circulation of novel RF-like Borrelia species with different associated tick vectors.


Skuballa J.,Karlsruhe Institute of Technology | Petney T.,Karlsruhe Institute of Technology | Pfaffle M.,Karlsruhe Institute of Technology | Oehme R.,Baden Wuerttemberg State Health Office | And 4 more authors.
Ticks and Tick-borne Diseases | Year: 2012

In order to determine whether European hedgehogs (Erinaceus europaeus and E. roumanicus) play a role in the epidemiological cycle of Borrelia burgdorferi sensu lato in Central Europe and Great Britain, tissue samples of hedgehogs from Germany (n=211), Austria (n=4), the Czech Republic (n=22), and the UK (n=32) were tested for the presence of these tick-borne pathogens. PCR for amplification of the B. burgdorferi s.l.-specific 5S-23S intergenic spacer region as well as the outer surface protein A (ospA) gene were used. B. burgdorferi s.l. DNA was detected in 35 of the 259 E. europaeus and in 2 of 10 E. roumanicus. B. burgdorferi prevalences in E. europaeus ranged from 0% (UK) to 37.5% (Czech Republic), for E. roumanicus from 0% (Czech Republic) to 50.0% (Austria). Sequencing revealed the occurrence of 3 different B. burgdorferi genospecies in E. europaeus: B. afzelii was the dominant genospecies, followed by B. bavariensis (previously B. garinii OspA serotype 4) and B. spielmanii, the latter was detected for the first time in Hamburg (Germany). B. afzelii and B. bavariensis were also found in E. roumanicus. Our results suggest that hedgehogs modulate the epidemiology of certain species of the B. burgdorferi s.l. complex, potentially affecting the distribution and abundance of individual B. burgdorferi s.l. genospecies in various habitats. We hypothesise that juvenile or individuals with low immune competence in particular, have a high reservoir potential for the 3 genospecies identified here. © 2011 Elsevier GmbH.


Dehnert M.,Robert Koch Institute | Fingerle V.,National Reference Center for Borrelia | Klier C.,National Reference Center for Borrelia | Talaska T.,Institute for Tickborne Diseases | And 4 more authors.
PLoS ONE | Year: 2012

Background: Lyme borreliosis (LB) caused by spirochetes of the Borrelia burgdorferi sensu lato complex is the most common tick-borne disease in the northern hemisphere. Data on the distribution and on risk factors in Germany are sketchy. Methodology/Principal Findings: Blood samples of a nationwide population-based cross-sectional study from 2003-2006 in children and adolescents aged 1 to 17 years in Germany (KiGGS) were analysed (n = 12,614) to assess the seroprevalence of anti-Borrelia antibodies. Data from standardized interviews were used to assess potential risk factors. First, sera were screened for anti-Borrelia antibodies by ELISA. The overall prevalence was 4.8% (95% confidence interval (CI) 4.3-5.4%). Positive and borderline ELISA test results were confirmed by a line blot revealing a combined prevalence of 4.0% (95% CI 3.6-4.5%). Seroprevalence of ELISA was significantly higher in males (odds ratio (OR) = 1.37; CI 1.15-1.63) and in the southern part of Germany (OR = 1.41; CI 1.09-1.83), but significantly lower in children and adolescents with migration background (OR = 0.33; CI 0.24-0.44). Study participants from households with cats had a higher chance of seropositivity (OR = 6.7; CI 5.6-8.0). In a multivariable model the odds of seropositivity increases by 11% for every year of age for boys and 6% for girls. Conclusions/Significance: This survey is the first nationwide, representative seroprevalence survey of LB in children and young adolescents. The study shows that infections with Borrelia burgdorferi are endemic in all parts of Germany despite regional differences. Even at a young age children are exposed to tick bites including seropositivity. Encouraging a thorough check for ticks and promptly removal of ticks are the key public health strategies to reduce the risk of LB and other tick-borne diseases in children and adolescents. Further epidemiological studies are warranted to better understand the burden of disease related to LB. © 2012 Dehnert et al.


Rupprecht T.A.,Abteilung Radiologie | Fingerle V.,National Reference Center for Borrelia
Future Neurology | Year: 2011

Lyme disease is the most common human tick-borne disease in the northern hemisphere. This article describes the current knowledge of several aspects of Lyme neuroborreliosis. The epidemiology is reviewed first, with special respect to the difference between European and American disease. Then, the current knowledge about the pathogenesis of Lyme neuroborreliosis is presented, with emphasis on immune evasion strategies. Furthermore, the clinical picture of acute Lyme neuroborreliosis and the frequently discussed post-Lyme disease syndrome are critically discussed. The commonly used diagnostic strategies, as well as the relevance of the lymphocyte transformation test, CD57 +/CD3- cell count and CXCL13, are presented. Finally, the therapeutic options are described to give a balanced overview of all aspects of this disease. © 2011 Future Medicine Ltd.


von Wissmann B.,National Reference Center for Borrelia | von Wissmann B.,Robert Koch Institute | Hautmann W.,National Reference Center for Borrelia | Sing A.,National Reference Center for Borrelia | And 2 more authors.
International Journal of Medical Microbiology | Year: 2015

To date, only isolated incidences of human granulocytic anaplasmosis (HGA) have been reported in Europe. However, entomological studies in Bavaria, Germany showed a prevalence of Anaplasma phagocytophilum of between 2 and 9.5% in the tick vector Ixodes ricinus. In this study we assessed the risk of pathogenic A. phagocytophilum infection after a tick bite in Bavaria. The seroprevalence of anti- Borrelia burgdorferi sensu lato (s.l.) antibodies was investigated as an indicator of past exposure, seroconversion as actual exposure of participants to ticks.Patients with a tick bite in the preceding four weeks were recruited by participating doctors. Questionnaires on demographics, tick exposure and clinical signs were completed by patients and doctors, respectively. Two blood samples, taken at an interval of two weeks, were tested for antibodies against A. phagocytophilum and B. burgdorferi s.l.One of 107 recruited patients showed serological evidence of an acute infection of A. phagocytophilum but had no clinical signs. Four out of six patients with serological evidence of an acute B. burgdorferi s.l. infection, presented with erythema migrans. A seroprevalence of 7.5% for A. phagocytophilum and 13.1% for B. burgdorferi s.l. was detected. The comparatively high seroprevalence of B. burdorferi s.l. and A. phagocytophilum antibodies indicate frequent past exposure of participants to ticks. The finding of one acute infection of A. phagocytophilum in the absence of clinical signs, supports entomological evidence that the strains of A. phagocytophilum predominantly present in the Bavarian tick population may cause transient infections but are of low pathogenicity in humans. © 2015 Elsevier GmbH.


PubMed | National Reference Center for Borrelia, University of Medicine and Pharmacy, Cluj-Napoca, Clinic of Infectious Diseases, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca and Bavarian Health and Food Safety Authority
Type: Journal Article | Journal: Experimental & applied acarology | Year: 2016

The objective of this study was to evaluate different methods used for detection of Borrelia burgdorferi sensu lato (s.l.) in ticks: immunohistochemistry followed by focus floating microscopy (FFM) and real-time polymerase chain reaction (real-time PCR) targeting the ospA and hbb genes. Additionally, an optimized ospA real-time PCR assay was developed with an integrated internal amplification control (IAC) for the detection of inhibition in the PCR assay and was validated as an improved screening tool for B. burgdorferi. One hundred and thirty-six ticks collected from humans in a hospital from Cluj-Napoca, Romania, were investigated regarding genus, stage of development and sex, and then tested by all three assays. A poor quality of agreement was found between FFM and each of the two real-time PCR assays, as assessed by concordance analysis (Cohens kappa), whereas the agreement between the two real-time PCR assays was moderate. The present study argues for a low sensitivity of FFM and underlines that discordant results of different assays used for detection of B. burgdorferi in ticks are frequent.


PubMed | University of Neuchatel and National Reference Center for Borrelia
Type: Journal Article | Journal: Parasites & vectors | Year: 2016

Transmission from the vertebrate host to the arthropod vector is a critical step in the life-cycle of any vector-borne pathogen. How the probability of host-to-vector transmission changes over the duration of the infection is an important predictor of pathogen fitness. The Lyme disease pathogen Borrelia afzelii is transmitted by Ixodes ricinus ticks and establishes a chronic infection inside rodent reservoir hosts. The present study compares the temporal pattern of host-to-tick transmission between two strains of B. afzelii.Laboratory mice were experimentally infected via tick bite with one of two strains of B. afzelii: A3 and A10. Mice were repeatedly infested with pathogen-free larval Ixodes ricinus ticks over a period of 4 months. Engorged larval ticks moulted into nymphal ticks that were tested for infection with B. afzelii using qPCR. The proportion of infected nymphs was used to characterize the pattern of host-to-tick transmission over time.Both strains of B. afzelii followed a similar pattern of host-to-tick transmission. Transmission decreased from the acute to the chronic phase of the infection by 16.1 and 29.3% for strains A3 and A10, respectively. Comparison between strains found no evidence of a trade-off in transmission between the acute and chronic phase of infection. Strain A10 had higher lifetime fitness and established a consistently higher spirochete load in nymphal ticks than strain A3.Quantifying the relationship between host-to-vector transmission and the age of infection in the host is critical for estimating the lifetime fitness of vector-borne pathogens.


PubMed | Public Health Agency of Canada, University of Bath, University of Montréal and National Reference Center for Borrelia
Type: Journal Article | Journal: PloS one | Year: 2016

Different genotypes of the agent of Lyme disease in North America, Borrelia burgdorferi sensu stricto, show varying degrees of pathogenicity in humans. This variation in pathogenicity correlates with phylogeny and we have hypothesized that the different phylogenetic lineages in North America reflect adaptation to different host species. In this study, evidence for host species associations of B. burgdorferi genotypes was investigated using 41 B. burgdorferi-positive samples from five mammal species and 50 samples from host-seeking ticks collected during the course of field studies in four regions of Canada: Manitoba, northwestern Ontario, Quebec, and the Maritimes. The B. burgdorferi genotypes in the samples were characterized using three established molecular markers (multi-locus sequence typing [MLST], 16S-23S rrs-rrlA intergenic spacer, and outer surface protein C sequence [ospC] major groups). Correspondence analysis and generalized linear mixed effect models revealed significant associations between B. burgdorferi genotypes and host species (in particular chipmunks, and white-footed mice and deer mice), supporting the hypotheses that host adaptation contributes to the phylogenetic structure and possibly the observed variation in pathogenicity in humans.

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