Evaluation of under-testing and under-diagnosis of tick-borne encephalitis in Germany.

BACKGROUND: Tick-borne encephalitis (TBE), a viral infectious disease affecting the central nervous system, potentially resulting in prolonged neurological symptoms and other long-term sequelae. Case identification can be challenging as TBE can be associated with non-specific symptoms, and even in cases consistent with typical TBE symptoms, the rate of laboratory testing to confirm cases is unknown. This study assessed real-world TBE laboratory testing rates across Germany. METHODS: In this retrospective cross-sectional study, physicians provided data on TBE decision-making, laboratory testing (serological), and diagnostics behavior via in-depth qualitative interviews (N = 12) or a web-based quantitative survey of their patient medical records (N = 166). Hospital-based physicians who specialized in infectious disease, intensive care unit, emergency room, neurology, or pediatrics with experience managing and ordering testing for patients with meningitis, encephalitis, or non-specific central nervous system symptoms in the past 12 months were included. Data were summarized via descriptive statistics. TBE testing and positivity rates were assessed for the aggregate sample of 1400 patient charts and reported by presenting symptoms, region, and tick bite exposure. RESULTS: TBE testing rates ranged from 54.0% (non-specific neurological symptoms only) to 65.6% (encephalitis symptoms only); the percentage of TBE positive results ranged from 5.3% (non-specific neurological symptoms only) to 36.9% (meningitis symptoms only). TBE testing rates were higher among those with a tick bite history and/or who presented with headache, high fever, or flu-like symptoms. CONCLUSIONS: The findings of this study suggest that patients with typical TBE symptoms are likely under-tested, thus likely leading to under-diagnosis in Germany. To ensure appropriate case identification, TBE testing should be consistently integrated into routine practice for all patients who present with relevant symptoms or exposure to common risk factors.

Comparative analyses of biofilm formation among different Cutibacterium acnes isolates.

The Gram-positive anaerobic bacterium Cutibacterium acnes is a commensal of the human skin, but also an opportunistic pathogen that contributes to the pathophysiology of the skin disease acne vulgaris. Moreover, C. acnes, in addition to other skin-colonizing bacteria such as S. epidermidis and S. aureus, is an emerging pathogen of implant-associated infections. Notably, C. acnes isolates exhibit marked heterogeneity and can be divided into at least 6 phylotypes by multilocus sequence typing. It is becoming increasingly evident that biofilm formation is a relevant factor for C. acnes virulence, but information on biofilm formation by diverse C. acnes isolates is limited. In this study we performed a first comparative analysis of 58 diverse skin- or implant-isolates covering all six C. acnes phylotypes to investigate biofilm formation dynamics, biofilm morphology and attachment properties to abiotic surfaces. The results presented herein suggest that biofilm formation correlates with the phylotype, rather than the anatomical isolation site. IA1 isolates, particularly SLST sub-types A1 and A2, showed highest biofilm amounts in the microtiter plate assays, followed by isolates of the IC, IA2 and II phylotypes. Microscopic evaluation revealed well-structured three-dimensional biofilms and relatively high adhesive properties to abiotic surfaces for phylotypes IA1, IA2 and IC. Representatives of phylotype III formed biofilms with comparable biomass, but with less defined structures, whereas IB as well as II isolates showed the least complex three-dimensional morphology. Proteinase K- and DNase I-treatment reduced attachment rates of all phylotypes, therefore, indicating that extracellular DNA and proteins are critical for adhesion to abiotic surfaces. Moreover, proteins seem to be pivotal structural biofilm components as mature biofilms of all phylotypes were proteinase K-sensitive, whereas the sensitivity to DNase I-treatment varied depending on the phylotype.

Incidence, healthcare resource utilization and costs of hospitalized patients with tick-borne encephalitis (TBE) in Italy.

OBJECTIVE: Our study's objective was to assess the incidence trends and healthcare resource utilization of hospitalizations for Tick-Borne Encephalitis (TBE) and associated costs in Italy in order to improve public awareness and preventive measures. METHODS: This retrospective observational study was based on the Italian Ministry of Health's Hospital Discharge Record (HDR) database. Data were gathered across Italy from 2015 to 2019, selecting hospitalizations with ICD-9 code 063 related to TBE, both in primary and secondary diagnoses. For each year, we collected the following variables: number of hospitalizations, hospitalization rate, mortality rate, mean length of hospital stay, hospital ward, and cost of hospitalization. RESULTS: There were a total of 237 hospitalizations from 2015 to 2019; 62 % of those were male. The lowest number of TBE hospitalizations was in 2015 (21 cases, corresponding to 0.35 per million inhabitants), the highest in 2019 (64 cases, 1.04 per million inhabitants). The summer months saw a greater than average number of hospitalizations. For the years analyzed, the cumulative number of cases peaked in June (54 cases), July (46 cases), and August (35 cases). There were only two deaths registered in our study sample. TBE cases were mostly localized in the North-Eastern regions of Italy. TBE incidence during the study period in the most affected areas were: Autonomous Province of Trento, ranging from 11.2 to 42.3 per million inhabitants, Autonomous Province of South Tyrol, from 0 to 21.1 per million inhabitants, and Veneto Region, from 2.6 to 4.5 per million inhabitants. In the study period, the average length of hospital stay was largely stable ranging from 10.6 days to 12.8 days, with related costs ranging from 5,813.7 € to 7,352.5 €. CONCLUSIONS: According to our data, the majority of TBE hospitalizations occur in North-East Italy with an increasing trend over the analyzed period. Even though Italy has fewer TBE cases than other neighboring European countries, the health and economic impact can be high in the affected areas.

Incidence of Lyme Borreliosis in Germany: A retrospective observational healthcare claims study.

Lyme borreliosis (LB) is the most common tick-borne disease in Germany. Although the incidence of LB in Germany has been assessed in several studies, those studies either used data from statutory surveillance, which frequently underreport cases, or data from health claims databases, which may overestimate cases due to non-specific LB case definitions. Here, using a more specific case definition, we describe the incidence of medically-attended LB by disease manifestation, age group, and federal state for the period 2015-2019. Both inpatient and outpatient cases were analyzed from a claims database. To be eligible for inclusion, patients were required to have an LB specific ICD-10 GM diagnosis code plus an antibiotic prescription, and for disseminated manifestations, a laboratory test order additionally. LB cases were classified as erythema migrans (EM), or disseminated disease including Lyme arthritis (LA), Lyme neuroborreliosis (LNB), and all other disease manifestations (OTH). Between 2015 and 2019, the incidence of medically-attended LB cases ranged from 195.7/100,000 population per year (95% confidence interval [CI], 191.0 - 200.5) to 254.5/100,000 population per year (95% CI, 249.0 - 260.0) per year. The majority of cases (92.2%) were EM, while 2.8% presented as LA, 3.8% as LNB, and 1.2% as OTH. For both EM and disseminated disease, the incidence peaked in children aged 5-9 years and in older adults. By federal state, the incidence of medically-attended EM ranged from 74.4/100,000 population per year (95% CI, 71.9 - 77.0) per year in Hamburg, to 394.1/100,000 population per year (95% CI, 370.7 - 417.6) per year in Saxony, whereas for medically-attended disseminated disease, the highest incidence was in Thuringia, Saxony, and Bavaria (range: 22.0 [95% CI, 19.9 - 24.0] to 35.7 [95% CI, 34.7 - 36.7] per 100,000 population per year). This study comprehensively estimated the incidence of all manifestations of medically-attended LB and showed a high incidence of LB throughout Germany. Results from the study support performing epidemiological studies in all federal states to measure the burden of LB and to invest in public health interventions for prevention.

Effectiveness of Vaccination Against Tick-Borne Encephalitis in the Czech Republic, 2018-2022.

Background: Tick-borne encephalitis (TBE) is caused by the tick-borne encephalitis virus (TBEV). TBEV infection can cause symptoms of central nervous system (CNS) inflammation and result in severe consequences including death. TBE is an increasing health threat in the Czech Republic and elsewhere in Europe. In 2020, 23% of 3734 TBE cases reported to the European Centre for Disease Prevention and Control were from the Czech Republic. TBE vaccination is universally recommended in the Czech Republic, but a full analysis of TBE vaccine effectiveness (VE) in the Czech Republic has not been published. Methods: TBE is a notifiable disease in the Czech Republic with mandatory reporting of cases (i.e., laboratory-confirmed TBEV infected patient with symptoms of CNS inflammation) and vaccination history to public health authorities. TBE VE was estimated using the screening method utilizing public health surveillance data from 2018 to 2022 and online household surveys of the general population on TBE vaccine uptake conducted in 2019-2022. Results: In 2018-2022, 3648 TBE cases were reported in the Czech Republic; 98.1% (3105/3166) of TBE cases with known vaccination history were unvaccinated. Among 42,671 persons surveyed from the general population who had known TBE vaccination history, 66.5% were unvaccinated. VE against TBE was 97.6% (95% confidence interval 95.7-98.7). When stratified by age group, VE was 97.1% (88.4-99.3) in 1-15 years of age, 97.9% (95.3-99.0) in 16-59 years of age, and 96.9% (90.5-99.0) in ≥60 years of age. TBE vaccination averted an estimated 1020 TBE cases in the Czech Republic from 2018 to 2022. Conclusions: This first published study with a full analysis of TBE VE in the Czech Republic showed that vaccination was highly effective for the prevention of TBE including in children, an age group with increasing TBE disease burden. Vaccination averted hundreds of TBE cases and hospitalizations despite the relatively low compliance with TBE vaccine recommendations. To prevent additional TBE cases in the Czech Republic, enhanced efforts to increase TBE vaccine uptake are needed.

Vaccine uptake in 20 countries in Europe 2020: Focus on tick-borne encephalitis (TBE).

Vaccination as a highly effective measure to protect against tick-borne encephalitis (TBE) comes into new focus as known risk areas are expanding across Europe and Asia. Here we present an online household survey conducted in 20 European countries spanning endemic and non-endemic regions of TBE in 2020. With a comprehensive and standardized list of questions, this survey provided a unique opportunity to compare TBE/TBE vaccine awareness, TBE severity perception, vaccine uptake, vaccination completeness/compliance and motivators/barriers for vaccination across Europe. Among the 51,478 participants, tetanus- (72-92%), influenza- (83-98%), and measles-awareness (79-96%) were highest, but awareness was low for Lyme borreliosis, bacterial meningitis and pneumococcal pneumonia. Awareness towards TBE and a TBE vaccine was 74% and 56% in endemic countries, respectively, compared to 30% and 12% in non-endemic countries. Vaccine uptake defined as at least one TBE vaccination was found to be highly heterogenous across both endemic (range 7-81%) and non-endemic countries (range 1-8%). Compliance with the recommended vaccination schedule was 21% for the primary vaccination series and dropped to 7% for the first booster vaccination in endemic countries. The percentage of participants protected against TBE by vaccination at the time of the survey ranged from 21% in Slovakia to 69% in Lithuania. The perception of personal risk or lack thereof was found to be the most influencing factor for and against TBE vaccination. Overall, these data indicate highly heterogenous responses in different European countries regarding not only awareness towards a TBE vaccine, but also regarding TBE vaccine uptake and compliance. Regionally focused strategies to increase diagnostic completeness as well as TBE vaccination are needed across Europe.

The Incidence of Lyme Borreliosis Among Children.

BACKGROUND: First recognized in children in the United States, Lyme borreliosis (LB) is the most prevalent tickborne illness in North America and Europe. However, the incidence of LB in children, including geographic variation and difference from that in adults, is incompletely described. METHODS: We compiled surveillance data from public health agency websites reporting age-stratified LB case data, which was combined with census data to derive incidence estimates. Additional incidence estimates were obtained through a systematic literature review. RESULTS: We identified 18 surveillance systems and 15 published studies for derivation of LB incidence in children. National incidence of >10 cases in children per 100,000 per year were estimated for the United States and parts of Eastern, Western and Northern Europe. However, there was substantial variation in incidence among countries in some European regions. National incidence estimates from the literature largely aligned with estimates from surveillance. Surveillance-reported pediatric incidence was lower than adult incidence in adults in 8 countries, similar to adult incidence in 3 countries, and higher than adult incidence in 1 country. Among all pediatric age strata, the 5-9 years of age stratum had the highest proportion of pediatric cases in most countries. CONCLUSIONS: As pediatric LB represents a substantial proportion of overall LB incidence across countries in Europe and North America, LB prevention and control efforts should target pediatric as well as adult populations. However, better data are needed to fully characterize the difference in incidence across geographic regions.

A systematic literature review of the effectiveness of tick-borne encephalitis vaccines in Europe.

BACKGROUND: Tick-borne encephalitis (TBE) is an infectious disease caused by the tick-borne encephalitis virus (TBEV) in patients with symptoms of central nervous system (CNS) inflammation. More than 25 European countries have one or more TBE-endemic areas. Although two TBE vaccines, FSME-IMMUN® and Encepur®, are commonly used in Europe, there are no published reviews of the real-world effectiveness of TBE vaccines in Europe or elsewhere. METHODS: We searched PubMed for TBE vaccine effectiveness (VE) articles and extracted information on country, study design, study period, study population, number of TBEV-infected cases, number of participants, and VE against TBEV infection and outcomes. RESULTS: We identified 13 studies, conducted in Austria, the Czech Republic, Latvia, Germany, and Switzerland, published in 2003-2023. One study was a cohort investigation of a milk-borne outbreak. In the other studies, 11 (91.7%) used the screening method and two (16.7%) used a case-control design (one study used both). TBE vaccines were highly effective (VE estimates >92%) against TBEV infection in all age groups. Vaccines were also highly protective against mild infections (i.e., infections in patients without symptoms of CNS inflammation), and against infections resulting in TBE and hospitalization. Vaccines were also highly protective against the most serious outcomes such as hospitalization greater than 12 days. Product-specific VE estimates were also high, though limited data were available. Studies in Austria, the Czech Republic, Latvia, and Switzerland estimated that TBE vaccines prevented >1,000 TBE cases a year, avoiding many hospitalizations and deaths, in these countries combined. CONCLUSIONS: Published VE studies demonstrate a high real-world effectiveness of the commercially available TBE vaccines in Europe. Although cases averted have been estimated in only four countries, TBE vaccination prevents thousands of cases in Europe each year. To prevent life-threatening TBE, TBE vaccine uptake and compliance with the vaccination schedule should be increased in residents of, and travelers to, TBE-endemic countries in Europe.

Incidence of Lyme Borreliosis in Finland: Exploring Observed Trends Over Time Using Public Surveillance Data, 2015-2020.

Background: Lyme borreliosis (LB) is a tick-borne zoonotic disease endemic in many European countries, including Finland. We describe the incidence, time trends, and geographical distribution of LB in Finland for the period 2015-2020. The data generated can help inform public health policy, including prevention strategies. Methods: We retrieved online-available LB cases and incidence from two Finnish national databases. Microbiologically confirmed LB cases were identified from the National Infectious Disease Register and clinically diagnosed LB cases from the National Register of Primary Health Care Visits (Avohilmo), with the total LB cases equal to the sum from these two sources. Results: A total of 33,185 LB cases were reported for the 2015-2020 period, of which 12,590 (38%) were microbiologically confirmed and 20,595 (62%) were clinically diagnosed. The average annual national incidences for total, microbiologically confirmed, and clinically diagnosed LB were, respectively, 99.6, 38.1, and 61.4 per 100,000 population. The total LB incidence was highest in the south to southwestern coastal areas by the Baltic Sea and in eastern areas, with average annual incidences of 109.0 to 207.3/100,000. The Åland Islands were a hyperendemic region with an average annual incidence of 2473.9/100,000. The highest incidence was among persons aged >60 years, peaking at age 70-74 years. Most cases were reported between May and October, with a peak in July and August. Conclusions: The incidence of LB varied substantially by hospital district, and many regions reached incidences comparable with other high incidence countries, suggesting preventive measures such as vaccines may be an efficient use of resources.

The Landscape of Lyme Borreliosis Surveillance in Europe.

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.

Epidemiology of Lyme Borreliosis in France in Primary Care and Hospital Settings, 2010-2019.

Introduction: Lyme borreliosis (LB) is a growing public health concern requiring accurate and comprehensive epidemiological knowledge to inform health care interventions. This study compared the epidemiology of LB in primary care and hospital settings, using for the first time in France three sources of data, and highlighted specific populations at higher risk of developing LB. Methods: This study analyzed data from general practitioner networks (i.e., Sentinel network, Electronic Medical Records [EMR]) and the national hospital discharge database to describe the LB epidemiology from 2010 to 2019. Results: The average annual incidence rates of LB in primary care increased from 42.3 cases/100,000 population in 2010-2012 to 83.0/100,000 in 2017-2019 for the Sentinel Network and 42.7/100,000 to 74.6/100,000 for the EMR, following a marked rise in 2016. The annual hospitalization rate remained stable from 2012 to 2019 fluctuating between 1.6 and 1.8 hospitalizations/100,000. Women were more likely to present with LB in primary care setting compared with men (male-to-female incidence rate ratio [IRR] = 0.92), whereas men were predominant among hospitalizations (IRR = 1.4), with the largest discordance among adolescents aged 10-14 years (IRR = 1.8) and adults aged 80 years and older (IRR = 2.5). In 2017-2019, the average annual incidence rate peaked among persons aged 60-69 years in primary care (>125/100,000) and aged 70-79 years among hospitalized patients (3.4/100,000). A second peak occurred in children aged 0-4 or 5-9 years depending on sources. Incidence rates in Limousin and the north-eastern regions were the highest for both primary care and hospital settings. Conclusions: Analyses showed disparities in the evolution of incidence, sex-specific incidence rates, and predominant age groups between primary care and hospital settings that merit further exploration.

Estimated Number of Symptomatic Lyme Borreliosis Cases in Adults in Finland in 2021 Using Seroprevalence Data to Adjust the Number of Surveillance-Reported Cases: A General Framework for Accounting for Underascertainment by Public Health Surveillance.

Background: Finland conducts public health surveillance for Lyme borreliosis (LB) based on clinically diagnosed and laboratory-confirmed cases. We used data from seroprevalence studies to determine the extent to which LB cases were underascertained by public health surveillance. Methods: The numbers of incident symptomatic LB cases in 2011 in six regions in Finland were estimated using (1) data from Borrelia burgdorferi sensu lato seroprevalence studies, (2) estimates of the proportion of LB infections that are asymptomatic, and (3) estimates of the duration of LB antibody detection. The numbers of estimated incident symptomatic LB cases were compared with the numbers of surveillance-reported LB cases to estimate regional underascertainment multipliers. Underascertainment multipliers were applied to the numbers of surveillance-reported LB cases in each region in 2021 and summed to estimate the number of symptomatic LB cases in Finland among adults in 2021. A sensitivity analysis evaluated the impact of different durations of antibody detection. Results: Using an asymptomatic proportion of 50% and a 10-year duration of antibody detection, the estimated regional underascertainment multipliers in Finland ranged from 1.0 to 12.2. Applying the regional underascertainment multipliers to surveillance-reported LB cases in each region and summing nationally, there were 19,653 symptomatic LB cases in Finland among adults in 2021 (526/100,000 per year). With 7,346 surveillance-reported LB cases in Finland among adults in 2021, the estimated number of symptomatic LB cases indicate that there were 2.7 symptomatic LB cases for every surveillance-reported LB case among adults. With a 5- or 20-year duration of antibody detection, there were an estimated 36,824 or 11,609 symptomatic LB cases among adults in 2021, respectively. Discussion: Finland has robust public health surveillance for LB, but cases are underascertained. This framework for estimating LB underascertainment can be used in other countries that conduct LB surveillance and have conducted representative LB seroprevalence studies.

Prospective incidence epidemiology study protocol: conducting active surveillance to assess the burden of Lyme disease (BOLD) in primary care practices in endemic areas of six European countries.

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.

Incidence of Lyme Borreliosis in Germany: Exploring Observed Trends Over Time Using Public Surveillance Data, 2016-2020.

Background: Public surveillance of Lyme borreliosis (LB) occurs in 9 out of 16 federal states of Germany and remains a critical facet of disease epidemiology and trends. We describe the incidence, time trends, seasonality, and geographic distribution of LB in Germany using publicly reported surveillance data. Methods: We obtained LB cases and incidence (2016-2020) from the online platform SurvStat@RKI 2.0, maintained by the Robert Koch Institute (RKI). Data included clinically diagnosed and laboratory-confirmed LB reported by nine out of 16 federal states of Germany where LB notification is mandatory. Results: During 2016-2020, the nine federal states reported 63,940 LB cases, of which 60,570 (94.7%) were clinically diagnosed, and 3370 (5.3%) also had laboratory confirmation, with an average of 12,789 cases annually. Incidence rates were mostly stable over time. The average annual LB incidence was 37.2/100,000 person-years and varied by spatial level, ranging from 22.9 to 64.6/100,000 person-years among nine states; from 16.8 to 85.6/100,000 person-years among 19 regions; and from 2.9 to 172.8/100,000 person-years among 158 counties. Incidence was lowest among persons 20-24 years old (16.1/100,000 person-years) and highest among those 65-69 years old (60.9/100,000 person-years). Most cases were reported between June and September, with a peak in July of every year. Conclusion: The risk of LB varied substantially at the smallest geographic unit and by age group. Our results underscore the importance of presenting LB data at the most spatially granular unit and by age to allow implementation of efficient preventive interventions and reduction strategies.

Seroprevalence of Lyme Borreliosis in Europe: Results from a Systematic Literature Review (2005-2020).

Background: Lyme borreliosis (LB), a tick bite-transmitted infection caused by Borrelia burgdorferi sensu lato (Bbsl) complex spirochetes, is the most common tickborne disease in Europe. Studies in European countries have reported LB seroprevalence (prevalence of antibodies to Bbsl infection) and diagnostic strategies used for testing. We conducted a systematic literature review to summarize contemporary LB seroprevalence in Europe. Methods: PubMed, Embase, and CABI Direct (Global Health) databases were searched from 2005 to 2020 to identify studies reporting LB seroprevalence in European countries. Reported single-tier and two-tier test results were summarized; algorithms (standard or modified) were used to interpret final test results from studies that used two-tier testing. Results: The search yielded 61 articles from 22 European countries. Studies used a range of diagnostic testing methods and strategies (48% single-tier, 46% standard two-tier, and 6% modified two-tier). In 39 population-based studies, of which 14 were nationally representative, seroprevalence estimates ranged from 2.7% (Norway) to 20% (Finland). There was substantial heterogeneity among studies in terms of design, cohort types, periods sampled, sample sizes, and diagnostics, which limited cross-study comparisons. Nevertheless, among studies that reported seroprevalence in persons with greater exposure to ticks, LB seroprevalence was higher among these groups than in the general population (40.6% vs. 3.9%). Furthermore, among studies that used two-tier testing, general population LB seroprevalence was higher in Western Europe (13.6%) and Eastern Europe (11.1%) than in Northern Europe (4.2%) and Southern Europe (3.9%). Conclusion: Despite variations in LB seroprevalence between and within European subregions and countries, high seroprevalence was observed in certain geographic regions and particular risk groups, suggesting significant disease burden and supporting the need for improved, targeted public health interventions such as vaccination. Harmonized approaches to serologic testing and more nationally representative seroprevalence studies are needed to better understand the prevalence of Bbsl infection in Europe.

Incidence of Lyme Borreliosis in the Dutch General Practice Population: A Large-Scale Population-Based Cohort Study Across the Netherlands Between 2015 and 2019.

Background: There is a need for updated incidence rates (IRs) of Lyme borreliosis (LB) in Europe, including the Netherlands. We estimated LB IRs stratified by geographic area, year, age, sex, immunocompromised status, and socioeconomic status (SES). Methods: All subjects registered in the PHARMO General Practitioner (GP) Database without prior diagnosis of LB or disseminated LB and having ≥1 year of continuous database enrolment were included. IRs and corresponding confidence intervals (CIs) of GP-recorded LB, erythema migrans (EM), and disseminated LB were estimated during the period 2015‒2019. Results: We identified 14,794 events (suspected, probable, or confirmed) with a diagnostic code for LB that included 8219 with a recorded clinical manifestation: 7985 (97%) with EM and 234 (3%) with disseminated LB. National annual LB IRs were relatively consistent, ranging from 111 (95% CI 106‒115) in 2019 to 131 (95% CI 126‒136) in 2018 per 100,000 person-years. Incidence of LB showed a bimodal age distribution, with peak IRs observed among subjects aged 5‒14 and 60‒69 years in men and women. Higher LB incidence was found in subjects who were residents of the provinces of Drenthe and Overijssel, immunocompromised, or of lower SES. Similar patterns were observed for EM and disseminated LB. Conclusions: Our findings confirm that LB incidence remains substantial throughout the Netherlands with no indication of decline in the past 5 years. Foci in two provinces and among vulnerable populations suggest potential initial target groups for preventive strategies such as vaccination.

A Retrospective Database Study of Lyme Borreliosis Incidence in Poland from 2015 to 2019: A Public Health Concern.

Background: In Poland, Lyme borreliosis (LB) has been subject to mandatory public health surveillance since 1996 and, in accordance with EU regulations, Lyme neuroborreliosis has been reported to the European Centre for Disease Prevention and Control since 2019. In this study, the incidence, temporal trends, and geographic distribution of LB and its manifestations in Poland are described for the period 2015-2019. Methods: This retrospective incidence study of LB and its manifestations in Poland was based on data sent to the National Institute of Public Health-National Institute of Hygiene-National Research Institute (NIPH-NIH-NRI) by district sanitary epidemiological stations using the electronic Epidemiological Records Registration System and data from the National Database on Hospitalization. Incidence rates were calculated using population data from the Central Statistical Office. Results: During 2015-2019, Poland reported 94,715 cases of LB with an overall average incidence of 49.3 cases per 100,000 population. Cases increased from 2015 (11,945) to 2016 (20,857) and then remained stable through 2019. Hospitalization due to LB also rose during these years. LB was more common among women (55.7%). Erythema migrans and Lyme arthritis were the most common manifestations of LB. The highest incidence rates occurred among >50-year-olds, with a peak in 65-69-year-olds. The highest number of cases was recorded in the third and fourth quarters of the year (July-December). Incidence rates in the eastern and northeastern regions of the country were higher than the national average. Conclusions: LB is endemic in all regions of Poland, and many regions reported high incidence rates. Large variations in spatially granular incidence rates highlight the need for targeted prevention strategies.

Incidence of Lyme Borreliosis in Europe from National Surveillance Systems (2005-2020).

Background: Lyme borreliosis (LB) is the most common tick-borne disease in Europe. To inform European intervention strategies, including vaccines under development, we conducted a systematic review for LB incidence. Methods: We searched publicly available surveillance data reporting LB incidence in Europe from 2005 to 2020. Population-based incidence was calculated as the number of reported LB cases per 100,000 population per year (PPY), and high LB risk areas (incidence >10/100,00 PPY for 3 consecutive years) were estimated. Results: Estimates of LB incidence were available for 25 countries. There was marked heterogeneity in surveillance systems (passive vs. mandatory and sentinel sites vs. national), case definitions (clinical, laboratory, or both), and testing methods, limiting comparison across countries. Twenty-one countries (84%) had passive surveillance; four (Belgium, France, Germany, and Switzerland) used sentinel surveillance systems. Only four countries (Bulgaria, France, Poland, and Romania) used standardized case definitions recommended by European public health institutions. Among all surveillance systems and considering any case definition for the most recently available years, national LB incidences were highest in Estonia, Lithuania, Slovenia, and Switzerland (>100 cases/100,000 PPY), followed by France and Poland (40-80/100,000 PPY), and Finland and Latvia (20-40/100,000 PPY). Incidences were lowest in Belgium, Bulgaria, Croatia, England, Hungary, Ireland, Norway, Portugal, Romania, Russia, Scotland, and Serbia (<20/100,000 PPY). At the subnational level, highest LB incidences (>100/100,000 PPY) were observed in areas of Belgium, Czech Republic, France, Germany, and Poland. Overall, on average 128,888 cases are reported annually. An estimated 202/844 million (24%) persons in Europe reside in areas of high LB incidence and 202/469 million (43.2%) persons reside in areas of high LB incidence among countries with surveillance data. Conclusion: Our review showed substantial variability in reported LB incidence across and within European countries, with highest incidences reported from the Eastern, Northern (Baltic states and Nordic countries), and Western Europe surveillance systems. Standardization of surveillance systems, including wider implementation of common case definitions, is urgently needed to interpret the range of differences in LB incidence observed across European countries.

Incidence of Lyme Borreliosis in Europe: A Systematic Review (2005-2020).

Background: Lyme borreliosis (LB) is the most common tick-borne disease in Europe, but the burden of disease is incompletely described. Methods: We conducted a systematic review across PubMed, EMBASE, and CABI Direct (Global Health) databases, from January 1, 2005, to November 20, 2020, of epidemiological studies reporting incidence of LB in Europe (PROSPERO, CRD42021236906). Results: The systematic review yielded 61 unique articles describing LB incidence (national or subnational) in 25 European countries. Substantial heterogeneity in study designs, populations sampled, and case definitions restricted data comparability. The European Union Concerted Action on Lyme Borreliosis (EUCALB)-published standardized LB case definitions were used by only 13 (21%) of the 61 articles. There were 33 studies that provided national-level LB incidence estimates for 20 countries. Subnational LB incidence was available from an additional four countries (Italy, Lithuania, Norway, and Spain). The highest LB incidences (>100 cases per 100,000 population per year [PPY]) were reported in Belgium, Finland, the Netherlands, and Switzerland. Incidences were 20-40/100,000 PPY in the Czech Republic, Germany, Poland, and Scotland and <20/100,000 PPY in Belarus, Croatia, Denmark, France, Ireland, Portugal, Russia, Slovakia, Sweden, and the United Kingdom (England, Northern Ireland, and Wales); markedly higher incidences were observed at the subnational level (up to 464/100,000 PPY in specific local areas). Conclusions: Although countries in Northern (Finland) and Western (Belgium, the Netherlands, and Switzerland) Europe reported the highest LB incidences, high incidences also were reported in some Eastern European countries. There was substantial subnational variation in incidence, including high incidences in some areas of countries with low overall incidence. This review, complemented by the incidence surveillance article, provides a comprehensive view into LB disease burden across Europe that may guide future preventive and therapeutic strategies-including new strategies on the horizon.

Estimated Incidence of Symptomatic Lyme Borreliosis Cases in Lublin, Poland in 2021.

Lyme borreliosis (LB), the most common tick-borne disease in Europe, is endemic to Poland. Despite public health surveillance with mandatory reporting of LB cases by physicians and laboratories, many symptomatic LB cases are not included in surveillance in Poland. We estimated the extent of the under-ascertainment of symptomatic LB cases via surveillance in the Polish province of Lublin to better understand Poland's LB burden. The number of incident symptomatic LB cases in Lublin in 2010 was estimated from two seroprevalence studies conducted among adults in Lublin, as well as estimates of the proportion of asymptomatic LB cases and the duration of LB antibody persistence. The estimated number of incident symptomatic LB cases was compared to the number of surveillance-reported cases in Lublin to derive an under-ascertainment multiplier. This multiplier was applied to the number of surveillance-reported cases in 2021 to estimate the number and population-based incidence of symptomatic LB cases in Lublin in 2021. We estimate that there are 5.9 symptomatic LB cases for every surveillance-reported LB case in Lublin. Adjusting for under-ascertainment, the estimated number of symptomatic LB cases in Lublin in 2021 was 6204 (population-based incidence: 467.6/100,000). After adjustment for under-ascertainment, the incidence of symptomatic LB in Lublin, Poland, is high.