Opinion: Methodological Shortcomings in the Study on a Prophage-based PCR Test for Lyme Borreliosis.
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SUBMITTER: van de Schoor FR
PROVIDER: S-EPMC8710760 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Opinion: Methodological Shortcomings in the Study on a Prophage-based PCR Test for Lyme Borreliosis.
van de Schoor Freek R FR Baarsma M E ME Leeflang Mariska M G MMG Fingerle Volker V Margos Gabriele G Hovius Joppe W JW van Dam Alje P AP
Frontiers in microbiology 20211213
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Project description:BackgroundLyme borreliosis (LB) is a tick-borne disease caused by spirochetes belonging to the Borrelia burgdorferi sensu lato species. Due to a variety of clinical manifestations, diagnosing LB can be challenging, and laboratory work-up is usually required in case of disseminated LB. However, the current standard of diagnostics is serology, which comes with several shortcomings. Antibody formation may be absent in the early phase of the disease, and once IgG-seroconversion has occurred, it can be difficult to distinguish between a past (cured or self-cleared) LB and an active infection. It has been postulated that novel cellular tests for LB may have both higher sensitivity earlier in the course of the disease, and may be able to discriminate between a past and active infection.MethodsVICTORY is a prospective two-gate case-control study. We strive to include 150 patients who meet the European case definitions for either localized or disseminated LB. In addition, we aim to include 225 healthy controls without current LB and 60 controls with potentially cross-reactive conditions. We will perform four different cellular tests in all of these participants, which will allow us to determine sensitivity and specificity. In LB patients, we will repeat cellular tests at 6 weeks and 12 weeks after start of antibiotic treatment to assess the usefulness as 'test-of-cure'. Furthermore, we will investigate the performance of the different cellular tests in a cohort of patients with persistent symptoms attributed to LB.DiscussionThis article describes the background and design of the VICTORY study protocol. The findings of our study will help to better appreciate the utility of cellular tests in the diagnosis of Lyme borreliosis.Trial registrationNL7732 (Netherlands Trial Register, trialregister.nl).
| S-EPMC6700813 | biostudies-literature
Project description:We investigated the epidemiology of Lyme borreliosis (LB) in Finland for the period 1995-2014 by using data from 3 different healthcare registers. We reviewed data on disseminated LB cases from the National Infectious Diseases Register (21,051 cases) and the National Hospital Discharge Register (10,402 cases) and data on primary LB (erythema migrans) cases from the Register for Primary Health Care Visits (11,793 cases). Incidence of microbiologically confirmed disseminated LB cases increased from 7/100,000 population in 1995 to 31/100,000 in 2014. Incidence of primary LB cases increased from 44/100,000 in 2011 to 61/100,000 in 2014. Overall, cases occurred predominantly in women, and we observed a bimodal age distribution in all 3 registers. Our results clearly demonstrate that the geographic distribution of LB has expanded in Finland and underscore the importance of LB as an increasing public health concern in Finland and in northern Europe in general.
| S-EPMC5547811 | biostudies-literature
Project description:We aimed to determine the presence of Ixodes ricinusticks in heavily populated areas of the Po River Valley after report of a Lyme disease case. Eighteen percent of ticks examined from 3 locations were positive for Lyme disease borreliae. Lyme disease was diagnosed for 3 workers at risk for tick bite.
| S-EPMC3298309 | biostudies-literature
Project description: Not available
| S-EPMC4592300 | biostudies-literature
Project description:Lyme borreliosis (LB) is not notifiable in many European countries, and accurate data on the incidence are often lacking. This study aimed to determine the seroprevalence of Borrelia burgdorferi sensu lato (s.l.)-specific antibodies in the general population of The Netherlands, and to determine risk factors associated with seropositivity. Sera and questionnaires were obtained from participants (n = 5592, aged 0-88 years) enrolled in a nationwide serosurveillance study. The sera were tested for B. burgdorferi s.l.-specific IgM and IgG antibodies using ELISA and immunoblot. Seroprevalence was estimated controlling for the survey design. Risk factors for seropositivity were analyzed using a generalized linear mixed-effect model. In 2016/2017, the seroprevalence in The Netherlands was 4.4% (95% CI 3.5-5.2). Estimates were higher in men (5.7% [95% CI 4.4-7.2]) than in women (3.1% [95% CI 2.0-4.0]), and increased with age from 2.6% (95% CI 1.4-4.4) in children to 7.7% (95% CI 5.9-7.9) in 60- to 88-year-olds. The seroprevalence for B. burgdorferi s.l. in the general population in The Netherlands was comparable to rates reported in European countries. The main risk factors for seropositivity were increasing age, being male and the tick bite frequency. The dynamics of LB infection are complex and involve variables from various disciplines. This could be further elucidated using infectious disease modelling.
| S-EPMC10143428 | biostudies-literature
Project description:BackgroundA single-tier immunoassay using the C6 peptide of VlsE (C6) from Borrelia burgdorferi sensu stricto (Bb) has been proposed as a potential alternative to conventional two-tier testing for the serologic diagnosis of Lyme disease in the United States and Europe.ObjectiveTo evaluate the performance of C6 peptide based multiplex Phosphorescence Analysis (PHOSPHAN) for the serologic confirmation of Lyme borreliosis (LB) in Russian patients.MethodsSerum samples (n = 351) were collected from 146 patients with erythema migrans (EM); samples from 131 of these patients were taken several times prior to treatment and at different stages of recovery. The control group consisted of 197 healthy blood donors and 31 patients with other diseases, all from the same highly endemic region of Russia. All samples were analyzed by PHOSPHAN for IgM and IgG to Bb C6, recombinant OspC and VlsE proteins, and C6 peptides from B. garinii and B. afzelii.ResultsIgM and IgG to Bb C6 were identified in 43 and 95 out of 131 patients (32.8 and 72.5%, respectively); seroconversion of IgM antibodies was observed in about half of the patients (51.2%), and of IgG antibodies, in almost all of them (88.4%). Additional detection of OspC-IgM and VlsE-IgM or IgG to C6 from B. garinii or B. afzelii did not contribute significantly to the overall sensitivity of the multiplex immunoassay.ConclusionsThe multiplex phosphorescence immunoassay is a promising method for simultaneously revealing the spectrum of antibodies to several Borrelia antigens. Detection of IgM and IgG to Bb C6 in the sera of EM patients provides effective serologic confirmation of LB and, with high probability, indicates an active infection process.
| S-EPMC4492927 | biostudies-literature
Project description:ObjectivesLyme serology does not readily discriminate an active Lyme borreliosis (LB) from a previous Borrelia infection or exposure. Here, we aimed to investigate a large number of immunological protein biomarkers to search for an immunological pattern typical for active LB, in contrast to patterns found in healthy blood donors, a proportion of whom were previously exposed to Borrelia.MethodsSerum samples from well-characterised adult patients with ongoing LB and healthy blood donors were included and investigated using a proximity extension assay (provided by Olink®) by which 92 different immune response-related human protein biomarkers were analysed simultaneously.ResultsIn total, 52 LB patients and 75 healthy blood donors were included. The blood donors represented both previously Borrelia exposed (n = 34) and not exposed (n = 41) based on anti-Borrelia antibody status. Ten of the examined 92 proteins differed between patients and blood donors and were chosen for further logistic regression (p<0.1). Six proteins were statistically significantly different between LB patients and blood donors (p<0.05). These six proteins were then combined in an index and analysed using receiver-operating-characteristic curve analysis showing an area under the curve of 0.964 (p<0.001).ConclusionsThe results from this study suggest that there is an immunological protein pattern that can distinguish a present Borrelia infection from a previous exposure as well as anti-Borrelia antibody negative blood donors. Although this method is not adapted for routine clinical use at this point, the possibility is interesting and may open new diagnostic opportunities improving the laboratory diagnostics of LB.
| S-EPMC10292690 | biostudies-literature
Project description:Purpose: Lyme borreliosis (LB) is the most prevalent tick-borne disease in Europe and the incidence of LB is increasing owing to an expansion in tick habitats. However, LB surveillance is quite heterogeneous across the continent, and for those countries with publicly available data, it is difficult to understand the differences in incidence between countries. The objective of our study was to summarize the publicly available data from surveillance for LB in the form of surveillance reports and/or dashboards and to compare the information available for various countries. Methods: We identified publicly available LB data (online dashboards and surveillance reports) in the European Union, European Economic Area, the United Kingdom, Russia, and Switzerland. Results: Of the 36 countries studied, 28 had LB surveillance in place; 23 had surveillance reports, and 10 had dashboards. The dashboards, in general, had more granular data compared with the surveillance reports, but the reports covered longer time periods. LB annual cases, incidence, age, and sex-stratified LB data; manifestations; and regional data were available for most of the countries. LB case definitions varied significantly among the countries. Conclusion: The study highlights large differences in LB surveillance systems, including representativeness, case definitions, type of data available that might inhibit comparison of data between countries and accurate determination of burden of disease, and risk groups within countries. Standardization of case definitions across countries would be a useful first step enabling comparisons between countries and contribute to recognizing the true burden of LB in Europe.
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Project description:This guideline of the German Dermatology Society primarily focuses on the diagnosis and treatment of cutaneous manifestations of Lyme borreliosis. It has received consensus from 22 German medical societies and 2 German patient organisations. It is the first part of an AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V.) interdisciplinary guideline: "Lyme Borreliosis - Diagnosis and Treatment, development stage S3". The guideline is directed at physicians in private practices and clinics who treat Lyme borreliosis. Objectives of this guideline are recommendations for confirming a clinical diagnosis, recommendations for a stage-related laboratory diagnosis (serological detection of IgM and IgG Borrelia antibodies using the 2-tiered ELISA/immunoblot process, sensible use of molecular diagnostic and culture procedures) and recommendations for the treatment of the localised, early-stage infection (erythema migrans, erythema chronicum migrans, and borrelial lymphocytoma), the disseminated early-stage infection (multiple erythemata migrantia, flu-like symptoms) and treatment of the late-stage infection (acrodermatitis chronica atrophicans with and without neurological manifestations). In addition, an information sheet for patients containing recommendations for the prevention of Lyme borreliosis is attached to the guideline.
| S-EPMC5588623 | biostudies-literature
Project description:Tick-borne diseases affecting humans and animals are on the rise worldwide. Vaccines constitute an effective control measure, but very few are available. We selected Lyme borreliosis, a bacterial infection transmitted by the hard tick Ixodes, to validate a new concept to identify vaccine candidates. This disease is the most common tick-borne disease in the Northern Hemisphere. Although attempts to develop a vaccine exist, none have been successfully marketed. In tick-borne diseases, the skin constitutes a very specific environment encountered by the pathogen during its co-inoculation with tick saliva. In a mouse model, we developed a proteomic approach to identify vaccine candidates in skin biopsies. We identified 30 bacterial proteins after syringe inoculation or tick inoculation of bacteria. Discovery proteomics using mass spectrometry might be used in various tick-borne diseases to identify pathogen proteins with early skin expression. It should help to better develop sub-unit vaccines based on a cocktail of several antigens, associated with effective adjuvant and delivery systems of antigens. In all vector-borne diseases, the skin deserves further investigation to better define its role in the elaboration of protective immunity against pathogens.
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