Introduction Lyme disease (LD) is the most frequent tick-borne disease in the moderate climates of Europe. This study will inform the phase III efficacy study for Pfizer and Valneva’s investigational Lyme disease vaccine, VLA15. VLA15 phase III will be conducted in the USA and Europe due to the vaccine’s serotype coverage and public health burden of LD. In Europe, the existence and location of sites that have access to populations with high LD annual incidence is uncertain. This active, prospective surveillance study assesses annual LD incidence at general practice (GP)/primary care sites, allowing for phase III site vetting and better characterisation of LD burden in selected regions for study size calculations. Methods and analysis This burden of Lyme disease (BOLD) study will assess LD incidence overall and by site at 15 GP/primary care practices in endemic areas of 6 European countries from Spring 2021 to December 2022 and will be summarised with counts (n), percentages (%) and associated 95% CIs. Suspected LD cases identified from site’s practice panels are documented on screening logs, where clinical LD manifestations, diagnoses and standard of care diagnostic results are recorded. In the initial 12-month enrolment phase, suspected LD cases are offered enrolment. Participants undergo interview and clinical assessments to establish medical history, final clinical diagnosis, clinical manifestations and quality of life impact. Study-specific procedures include LD serology, skin punch biopsies and Lyme manifestation photographs. For every enrolled participant diagnosed with LD, 6–10 age-matched controls are randomly selected and offered enrolment for an embedded LD risk factor analysis. Persistent symptoms or post-treatment LD will be assessed at follow-up visits up to 2 years after initial diagnosis, while patients remain symptomatic. Ethics and dissemination This study has been approved by all sites’ local ethics committees. The results will be presented at conferences and published in peer-reviewed journals.

Lyme borreliosis (LB), the most common European tick-borne disease, can manifest as an erythema migrans (EM) rash or as disseminated LB. The prospective Burden of Lyme Disease (BOLD) study evaluated the frequency of LB clinical manifestations, including signs, symptoms, and treatment patterns in 14 healthcare practices in endemic regions of six European countries: the Czech Republic, Germany, Poland, Slovakia, Slovenia, and Sweden. Between April 2021 and December 2022, patients with suspected LB were evaluated using predefined case definitions that were applied by investigators to identify medically attended LB cases. Enrolled cases were interviewed about their symptoms. Among the 797 LB cases, 615 (77.2%) had EM and 182 (22.8%) had disseminated disease; 154 of the disseminated cases had Lyme arthritis (LA), five had Lyme neuroborreliosis, and three had Lyme carditis. Geographically, the proportion of disseminated disease varied by country, from 1.1% in Slovenia to 78.0% in Slovakia. Overall, 76.3% of all LB cases in Slovakia were LA. Antibiotic use varied by country, although every country prescribed doxycycline. The frequency of LB manifestations varied substantially between countries. EM was the most common manifestation in all countries except Slovakia, where LA was most common. This study underscores the need for improved prevention strategies.

Introduction: Lyme borreliosis (LB), an infection caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. To further characterize the LB burden in the Czech Republic, we conducted a seroprevalence study and estimated the incidence of symptomatic Bbsl infections. Methods: Anti-Bbsl IgM and IgG antibodies were detected in sera collected from the adult population in 2011-2012 by enzyme-linked immunosorbent assay and immunoblot tests at the National Reference Laboratory. The incidence of symptomatic Bbsl infections was estimated from the seroprevalence results and the symptomatic proportion and duration of persistence of anti-Bbsl IgG antibodies in Bbsl-infected individuals. Surveillance under-detection of symptomatic Bbsl infections was estimated by comparing surveillance-reported and seroprevalence-based incidence. Results: Samples from 1996 adults were tested; the median age (range) was 45 (18-87) years; 1037 (52.0 %) were female. The prevalence (with 95 % confidence interval) of anti-Bbsl IgG, and IgM and/or IgG (IgM/IgG) antibodies was 6.3 % (5.3-7.5 %), and 9.5 % (8.3-10.9 %), respectively. The IgM/IgG prevalence was 7.8 % (6.5-9.2 %) in Bohemia and 15.3 % (12.2-19.0 %) in Moravia. There were an estimated 30,563 (26,550-34,962) symptomatic incident Bbsl infections in adults in the Czech Republic in 2012, for an incidence of 352.2 (306.0-402.9) symptomatic Bbsl infections per 100,000 adults per year. There were an estimated 11 (10-13) symptomatic Bbsl infections for each surveillance-reported LB case in the Czech Republic in 2012. Conclusions: There is high incidence of symptomatic Bbsl infections in the Czech Republic, particularly in Moravia. Interventions are needed to address the substantial burden of LB in the Czech Republic.

Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), is a significant public health concern in Switzerland. Reliable data on seroprevalence and incidence are needed to better understand disease burden and inform prevention strategies. This study aimed to estimate the seroprevalence of Bbsl-specific antibodies and the incidence of symptomatic LB infections in the Swiss adult population. We analyzed Bbsl-specific IgG antibodies in 2,194 residual plasma samples from blood donors (aged 18-75 years) collected at seven Swiss Red Cross donation centers between September and December 2022. Samples were tested using the Liaison® Borrelia IgG VlsE chemiluminescence immunoassay and confirmed with the SeraSpot Anti-Borrelia-10 IgG assay according to National Reference Laboratory interpretative criteria. The overall seroprevalence was 6.1%, with higher prevalence in males (8.2%) than in females (2.9%) and regional variation ranging from 1.6% in Genève to 8.8% in Bern. Based on seroprevalence data, the estimated incidence of symptomatic Bbsl infections was 224 cases per 100,000 population per year (PPY). This estimate, although 1.3 times higher, is similar to the incidence derived from the Sentinella surveillance network. Using Sentinella data, clinically diagnosed erythema migrans was the most common manifestation (150 cases per 100,000 PPY), while disseminated forms, confirmed by clinical and laboratory criteria, occurred less frequently (1.0-8.5 cases per 100,000 PPY). Our findings provide critical insights into the burden of LB in Switzerland, highlight its public health relevance, and reinforce the importance of preventive measures. Future research should focus on longitudinal monitoring and harmonized methodologies to facilitate cross-country comparisons.

Lyme borreliosis (LB) can manifest as a localized infection or, if left untreated, disseminated disease. This analysis used Patient-Reported Outcome tools to assess general health, fatigue, pain, and cognitive function in patients with localized or disseminated LB, compared with age- and site-matched controls without LB. All participants were enrolled in the Burden of Lyme Disease (BOLD) study; LB cases were assessed at 3 time points: the enrollment visit, and two follow-up visits conducted within 10 months of enrollment. Controls were evaluated at 2 time points: the enrollment contact and a follow-up contact 16–18 months post-enrollment. Symptom severity and general health quality between groups were compared using two-tailed Student’s t-tests and multivariate regression analyses. Disseminated LB cases reported greater fatigue and pain than localized LB (disseminated LB fatigue scores: 4.1, 3.7, and 3.5 at Visits 1, 2, and 3, respectively vs. localized LB: 2.9, 3.0, and 2.9; disseminated LB pain scores: 2.5, 1.6, and 1.3 vs. localized LB: 0.9, 0.6, and 0.8) and controls (fatigue score: 3.2; pain score: 1.0). Disseminated LB was also associated with reduced health-related quality of life. The results of this study indicate that health-related quality of life may vary by disease stage and that patients with disseminated disease showed persistent impairment during the acute phase and at 10-month follow-up.

Up to 10% of patients with Lyme borreliosis (LB) will experience symptoms that fulfill the Infectious Disease Society of America (IDSA) criteria of post-treatment Lyme disease syndrome (PTLDS). This study assesses PTLDS in the Burden of Lyme Disease (BOLD) study through clinical assessment (“PTLDS Assessed by Clinicians”) and by post hoc evaluation of patient-reported outcomes, including the 36-Item Short Form Health Survey, Fatigue Severity Scale, and Cognitive Failures Questionnaire (“PTLDS Assessed by Questionnaire”). Among 242 LB cases who completed antibiotic treatment and had objective manifestations stabilized or resolved, 99 (40.9%) reported ≥1 symptom of fatigue, musculoskeletal pain, or cognitive impairment 10 months after diagnosis. Fifteen (6.2%) cases met the PTLDS criteria assessed by either clinicians or predefined questionnaire severity thresholds; four (1.7%) met both. PTLDS cases assessed by questionnaires and LB cases with persistent symptoms both reported greater symptom severity and poorer physical functioning than PTLDS cases assessed by clinicians. These exploratory findings suggest that clinician- and questionnaire-based assessments may identify partially different subsets of patients with PTLDS and either method could underestimate the proportion of patients with PTLDS.