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Point-of-care serological and direct antigen testing offers actionable insights for diagnosing challenging illnesses, empowering distributed health systems. Here, we report a POC-compatible serologic test for Lyme disease (LD), leveraging synthetic peptides specific to LD antibodies and a paper-based platform for rapid, and cost-effective diagnosis. Antigenic epitopes conserved across Borrelia burgdorferi genospecies, targeted by IgG and IgM antibodies, are selected to develop a multiplexed panel for detection of LD antibodies from patient sera. Multiple peptide epitopes, when combined synergistically with a machine learning-based diagnostic model achieve high sensitivity without sacrificing specificity. Blinded validation with 15 LD-positive and 15 negative samples shows 95.5% sensitivity and 100% specificity. Blind testing with the CDCs LD repository samples confirms the test accuracy, matching lab-based two-tier results, correctly differentiating between LD and look-alike diseases. This LD diagnostic test could potentially replace the cumbersome two-tier testing, improving diagnosis and enabling earlier treatment while facilitating immune monitoring and surveillance.

Background: In Lyme-endemic areas, limited research has investigated the risk of tick-borne diseases among frontline workers in fire management. This study aimed to compare the exposure histories to ticks and tick-borne pathogens, knowledge, and prevention practices between individuals engaged in fire-related forest management and those participating in recreational activities within Santa Cruz County, CA, in an area of high risk of tick exposure. Methods: Blood samples from 55 forest workers and 58 members of the public were tested for bacterial DNA of and antibodies to Borrelia burgdorferi, Anaplasma phagocytophilum, and Rickettsia species. In addition, a questionnaire was administered to 54 workers and 84 members of the public to identify gaps in knowledge and prevention practices. Results: Although workers had a higher percentage of positive B. burgdorferi antibodies than the public (5.5% compared with 1.7%), the difference was not statistically significant. Conversely, rickettsial antibodies were more prevalent among the public (17.2% versus 3.6% for workers), but specificity to pathogenic bacteria could not be confirmed. No DNA for the three pathogens or antibodies against A. phagocytophilum were detected. Many workers and members of the public reported tick bites (67.4% of participants), with a notable 11% increase among workers in the odds of being bitten for each additional year spent working in forests. Although workers took greater precautions, significant knowledge and practice gaps were identified among both populations, such as an inability to distinguish tick species from common arthropods (mites, spiders, fleas), overestimating the size of ticks, and inappropriate tick-removal techniques. Conclusion: This study underscores the risk of tick-borne diseases faced by fire management workers in Lyme disease–endemic regions. The findings emphasize the necessity for future studies of Lyme disease within this population, and highlight the urgent need for enhanced training programs to minimize these risks. [ABSTRACT FROM AUTHOR]

Borrelia spp. are transmitted to humans by the bite of an infected tick. In Europe, Borrelia afzelii and Borrelia garinii are the main causative agents of Lyme borreliosis, one of the most prevalent tick-borne diseases in the northern hemisphere. In bacteria such as Borrelia spp., a restriction-modification system (RMS) protects against the harmful introduction of foreign DNA. The RMS comprises two activities: methyltransferase and endonuclease. This study is aimed to characterize the RMS of B. afzelii and B. garinii. First, we identified potential RMS genes. The predicted genes were cloned into a methylase-deficient Escherichia coli strain and digested with methylation-sensitive restriction enzymes to verify methyltransferase activity. Additionally, the RMS proteins were purified to evaluate endonuclease activity. Subsequently, methylated and unmethylated plasmids were used to investigate the effect of methylation on endonuclease activity and transformation efficiency. We identified four possible RMS genes in B. afzelii and four RMS genes in B. garinii. We analyzed the presence of these genes in patient isolates and observed a high degree of heterogeneity. The restriction pattern of DNA methylated by each of the four recombinantly expressed genes provided strong evidence that all encode adenine-specific methyltransferases. After 24 h of incubation with purified RMS proteins, we observed complete digestion of unmethylated plasmid DNA, demonstrating endonuclease activity. Finally, we proved that methylation protects against endonuclease activity and increases transformation efficiency. [ABSTRACT FROM AUTHOR]

Objectives: To investigate receipt of antibiotics among patients with neuroborreliosis after initial antibiotic treatment, likely attributable to posttreatment symptoms. Methods: We performed a nationwide, matched, population-based cohort study in Denmark (2009-2021). We included all Danish patients with neuroborreliosis, i.e. a positive Borrelia burgdorferi intrathecal antibody index test and a cerebrospinal fluid leukocyte count ≥10 × 106/l, and initially treated with doxycycline. To form a comparison cohort, we randomly extracted individuals from the general population matched 1:10 to patients with neuroborreliosis on date of birth and sex. The main outcome was receipt of doxycycline, and the secondary outcome was receipt of phenoxymethylpenicillin. We calculated short-term (<1 year) and long-term (≥1 year) hazard ratios (HR) with 95% confidence intervals (95%CI). Results: We included 463 patients with neuroborreliosis and 2,315 comparison cohort members. Compared with the comparison cohort members, patients with neuroborreliosis initially treated with doxycycline had increased receipt of additional doxycycline within 1 year (HR: 38.6, 95%CI: 17.5–85.0) and ≥1 years (HR: 3.5, 95%CI: 1.9–6.3). Compared with comparison cohort members, patients with neuroborreliosis had no increased receipt of phenoxymethylpenicillin (<1 year HR 1.0, 95%CI: 0.7–1.3; ≥1 years HR 1.2, 95%CI: 0.9–1.5). Conclusions: After initial antibiotic treatment, patients with neuroborreliosis have increased receipt of doxycycline particularly within one year after initial antibiotic therapy but also subsequently. The lack of increased receipt of phenoxymethylpenicillin suggests that the receipt of doxycycline was not merely due to differences in healthcare-seeking behaviour, increased risk of early Lyme borreliosis due to exposure, or differences in antibacterial usage in general. [ABSTRACT FROM AUTHOR]

Background: Lyme disease is a tick‐borne zoonotic disease caused by Borrelia burgdorferi sensu lato and is prevalent in northeastern Asia, particularly in the forested area of Northeastern China. However, a lack of systematic data on the spatial distribution of B. burgdorferi in this region hinders the prediction of its transmission risk across the landscape. Methods: To provide an updated overview and establish a comprehensive spatial distribution database, we conducted a systematic review of literature published between 2000 and 2022. We collected and compiled relevant data on B. burgdorferi in Northeastern China and its neighbouring regions, outlining its distribution in ticks, wild animals, livestock and humans. Spatial analysis was performed to identify spatial clusters of tick positivity and host infection rates. Results: From a total of 1823 literature, we selected 110 references to compile 626 detection records of B. burgdorferi, including 288 in ticks, 109 in wildlife, 111 in livestock and domestic animals and 100 in humans. The average detection rate of B. burgdorferi in ticks was approximately 20%, with wildlife, livestock and domestic animal host positivity rates below 50% and human seroprevalence rates varying from 0.94% to 44.18%. Conclusions: The study identified the presence of 17 tick species and ten genotypes of B. burgdorferi in the region, indicating a broad distribution. Notably, B. burgdorferi exhibited notable clustering, particularly in the central and eastern areas of Jilin Province, warranting further investigation. [ABSTRACT FROM AUTHOR]

Background and Aims: Lyme disease is a well‐known occupational risk across North America caused by exposure to Borrelia burgdorferi via blacklegged ticks (Ixodes scapularis). As the geographic range of B. burgdorferi advances with the increasing distribution of blacklegged ticks, more outdoor workers are at risk of contracting Lyme disease. In this study, we examined the demography and personal perceptions of outdoor workers within one framework to better determine the overall risk for those working outdoors. Methods and Results: We analysed outdoor worker knowledge of ticks and of behaviours that can prevent tick bites and Lyme disease. We then compared these risk perceptions of individuals across age, sex, education, and industry, as well as time spent outdoors. We tested the hypothesis that the risk perception of an individual and their knowledge of Lyme disease transmission was dependent on their demographics, experience in their job, and the region in which they spend time outdoors. We estimated a knowledge‐based risk score based on individuals' answers to a questionnaire on risk perception given to voluntary participants who work outdoors. Those who had higher risk scores were more at risk. We found that knowledge‐based risk scores were correlated with geographic risk levels and with the number of hours per day spent outdoors. Those who work longer hours and who work in areas with mid‐level risk had higher risk scores. Those who spend more time outdoors recreationally had lower risk scores. Conclusions: Further examination and acknowledgment of the reasoning behind why these factors are affecting workers' risks must be considered to recognize that it is not necessarily demographics or geographically high‐risk areas that affect an individual's risk. Workers' knowledge of these risks is affected by several variables that should be taken into consideration when implementing safety measures and awareness programs. [ABSTRACT FROM AUTHOR]

Introduction: The expanding geographical range of blacklegged ticks (BLTs), Ixodes scapularis, and its ability to transmit Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, and Borrelia miyamotoi poses an emerging public health risk. Our study determined the geographic distribution and the minimum infection rate (MIR) of B. burgdorferi‐, A. phagocytophilum‐, Ba. microti‐, and B. miyamotoi‐infected BLTs in Manitoba submitted to the Public Health Agency of Canada's passive tick surveillance programme from 1995 to 2017. Methods: Regression models were used to test the association of the MIR by year for each pathogen. Ticks were tested using PCR for B. burgdorferi since 1995, A. phagocytophilum since 2006, and Ba. microti and B. miyamotoi since 2013. The global positioning system coordinates of infected and uninfected ticks submitted during the surveillance period were plotted on a map of Manitoba using ArcGIS Pro version 3.1.2 to detect changes in the geographic distribution of ticks over time. Results: The overall MIR for B. burgdorferi was 139.7 (95% confidence interval [CI]: 129.0–150.5) per 1000 BLTs; however, it varied over time. After remaining stable from 1995 to 2005, the MIR increased by 12.1 per 1000 BLTs per year from 2005 to 2017 (95% CI: 7.0%–17.2%, p‐value <0.01). The geographic distribution of B. burgdorferi‐infected BLTs was centred around Winnipeg, Manitoba, and spread outward from this locality. The MIRs of A. phagocytophilum, Ba. microti, and B. miyamotoi were 44.8 per 1000 BLTs (95% CI: 38.1–51.6), 10.8 (95% CI: 6.6–15.0), and 5.2 (95% CI: 2.3–8.1) per 1000 BLTs, respectively, and showed no significant change over time. Conclusion: Passive surveillance revealed the presence of A. phagocytophilum‐, Ba. microti‐, and B. miyamotoi‐infected BLTs in southern Manitoba and revealed an increased risk of exposure to B. burgdorferi‐infected BLTs due to the increasing geographic range and MIR. [ABSTRACT FROM AUTHOR]

The incidence or prevalence of Lyme arthritis (LA) in Denmark is unknown and assumed very low. No published cases of polymerase chain reaction (PCR)-confirmed LA from Denmark exist. Clinically, LA does not differ from other rheumatic oligoarthritic disorders posing a differential diagnostic challenge. To review the incidence and prevalence of LA to our knowledge and to present a case series of PCR-confirmed LA cases from Denmark. We conducted a systematic literature review via MEDLINE and EMBASE to explore incidence and prevalence rates of LA. Additionally, we present six cases of patients diagnosed with LA in Denmark. Our literature review identified 23 studies reporting prevalence or incidence, yet only ten studies provided estimates ranging from 1.1 to 280/100.000 in the general population. Our case series identified six patients with LA from a localized region in Southern Denmark; all confirmed by Borrelia-specific real-time PCR from synovial fluid. The diagnostic delay was up to 38 months. All patients except one had a history of previous tick bites; none had erythema migrans lesions. All presented with recurrent arthritis in the knee joint, and two had arthritis in the wrist. The literature review showed an incidence of LA ranging from 1.1 to 15.8 per 100.000 in Europe. Our case series suggests a potentially higher prevalence of LA in Denmark than previously believed. Lack of tick exposure history, antibody assessments and test of Borrelia burgdorferi sensu lato DNA in synovial fluid might lead to misdiagnosed cases potentially explaining the assumed low incidence of LA in Denmark. [ABSTRACT FROM AUTHOR]

The genus Borrelia encompasses a diverse group of spirochetes transmitted primarily by ticks, with Borrelia burgdorferi causing Lyme disease, which is prevalent in North America and Europe. Borrelia's structural adaptations and ability to persist in diverse host tissues underscore its pathogenic potential. Beyond traditional infectious responses, Borrelia engages in complex interactions with the host immune system, contributing to autoimmune mechanisms such as molecular mimicry and persistent infections. This intricate interplay manifests in symptoms resembling various autoimmune diseases, including systemic lupus erythematosus, dermatomyositis, local scleroderma, and systemic sclerosis. However, these associations lack a precise explanation, emphasizing the need for further investigation. The cases of misdiagnosis between Lyme borreliosis and autoimmune diseases highlight the critical importance of accurate diagnostics and adherence to guidelines. Understanding Borrelia's impact on immune responses is pivotal for advancing diagnostics and targeted therapeutic interventions in Lyme borreliosis and its potential autoimmune implications. [ABSTRACT FROM AUTHOR]

Background: Microbial communities significantly influence the vector capacity of ticks, which, along with tick-borne diseases, pose an increasing global threat. Due to the substantial individual variability caused by various factors, it is essential to assess tick microbial communities and vectorial capacities under different environmental conditions. However, there is a relative scarcity of research on the microbial communities and pathogen transmission of ticks in different physiological states and environmental conditions, especially in Hainan Island, southern China. Methods: From 2021 to 2022, we collected 4,167 tick samples, grouping them by blood meal status, developmental stage, sex, time, geographical location, and tick species. We selected 128 samples for full-length 16S rRNA sequencing to describe microbial community characteristics and identify potential biomarkers. Seven hundred seventy-two samples were tested for seven tick-borne pathogens (Rickettsia, Borrelia burgdorferi, Ehrlichia, Anaplasma, Theileria, Babesia, and Hepatozoon), and sera from 208 residents of Hainan Island were tested for IgG antibodies against Rickettsia and B. burgdorferi. Results: Blood meal status, developmental stage, sex, time, geographical location, and tick species significantly influenced the microbial communities of ticks. We observed distinct microbial community characteristics across different states. We noted the non-random replacement of stable and transient species, with functional differences between parasitic and engorged ticks mainly driven by transient species. Functionally, we observed three distinct response patterns: driven by stable species, transient species, and both together in response to the six factors. We identified 273 potential biomarkers (200 robust core species and 73 robust differential species). Six genera and eight species of pathogens were detected in ticks, with an overall positivity rate of 12.44% (96/772). Among humans, 18.27% (38/208) of serum samples were positive for at least one tick-borne pathogen IgG. Conclusion: Our findings indicate that these six factors significantly influence both tick microbial communities and vectorial capacity, with varying effects on vector competence for different pathogens and inconsistent impacts on microbial communities under different conditions. This study supplemented the understanding of tick microbial communities on Hainan Island, assessed the relatively high risk of tick-borne pathogens in the region, and evaluated the impact of these factors on both microbial communities and vectorial capacity. [ABSTRACT FROM AUTHOR]

Background The prevalence of Babesia coinfecting tick-borne zoonoses and mortality outcomes are not fully elucidated. The objective of the present study was to determine babesiosis coinfection prevalence rates and estimate the association with severe disease and mortality. Methods We queried the TriNetX database between 2015 and 2022 for patients with babesiosis. The prevalence of Babesia coinfecting tick-borne zoonoses was estimated. The analysis focused on babesiosis coinfection with Borrelia burgdorferi , ehrlichiosis, and anaplasmosis. The exposure was coinfection, and the control group was the Babesia -only group. The primary outcome was 90-day mortality from the diagnosis of Babesia. Secondary outcomes were prevalence of coinfection, association of coinfection with acute respiratory distress syndrome, multiorgan failure, and disseminated intravascular coagulation. A multivariable logistic regression model was employed to estimate the disease severity and mortality risk associated with coinfections. Results Of the 3521 patients infected with Babesia , the mean age (SD) was 56 (18) years, 51% were male, and 78% were White. The frequency of overall malignancies, lymphomas, and asplenia was 19%, 2%, and 2%, respectively. Temporal distribution of coinfections followed the overall babesiosis pattern, peaking in the summer months. The prevalence of 1 or more coinfections was 42% (95% CI, 40%–43%). The rate of coinfection with Borrelia burgdorferi was the highest at 41% (95% CI, 39%–42%), followed by ehrlichiosis at 3.7% (95% CI, 3.1%–4.4%) and anaplasmosis at only 0.3% (95% CI, 0.2%–0.6%). Doxycycline was more likely to be prescribed in the coinfection group than the Babesia -only group (25% vs 18%; P <.0001). Overall, 90-day mortality was 1.4% (95% CI, 1.0%–1.8%). After adjusting for potential confounding factors, compared with the babesiosis-only group, the likelihood of 90-day mortality was lower in the coinfection group (adjusted odds ratio, 0.43; 95% CI, 0.20–0.91). Severe disease did not differ significantly between the 2 groups. Conclusions In this extensive study of >3000 patients with babesiosis in the United States, 4 in 10 patients had coinfecting tick-borne zoonoses. The prevalence rates of coinfection were highest with Borrelia burgdorferi, followed by ehrlichiosis, and lowest with anaplasmosis. Coinfection with other tick-borne infections was not associated with severe disease. It is plausible that this finding is due to the likelihood of treatment of coinfections with doxycycline. Future studies are needed to investigate the possible therapeutic benefits of doxycycline in babesiosis patients as, to date, no trials with doxycycline have been conducted in human patients with Babesia infections. [ABSTRACT FROM AUTHOR]

We evaluated spatial-temporal risk for Lyme disease in northwestern North Carolina, USA, by using individuallevel canine Borrelia burgdorferi seroprevalence data collected during 2017–2021 at routine veterinary screenings for tickborne diseases. Seroprevalence in dogs increased from 2.2% (47/2,130) in 2017 to 11.2% (339/3,033) in 2021. The percentage of incident seropositivity increased from 2.1% (45/2,130) in 2017 to 7.6% (231/3,033) in 2021. Exploratory geographic analyses found canine seroprevalence shifted from clustered (2017, Moran’s I = 0.30) to dispersed (2021, Moran’s I = −0.20). Elevation, slope, aspect, and forest land cover density were associated with canine seroprevalence within various household buffer regions in 2017. Slope was associated with seroprevalence at the household level in 2021. Results support the use of individual-level canine seroprevalence data for monitoring human risk for Lyme disease. Establishing sentinel veterinary clinics within Lyme disease–emergent communities might promote prevention and control efforts and provide opportunities for educational and behavioral interventions. [ABSTRACT FROM AUTHOR]

Lyme disease, the most prevalent tick‐borne disease in North America, is caused by the bacterium Borrelia burgdorferi, and in the eastern and central United States, it is spread to humans by the black‐legged tick (Ixodes scapularis). Due to the complex, multiyear and multihost life cycle of this species, a matrix modeling approach is needed to effectively estimate subseasonal, multistage survival and transition dynamics in order to better understand and predict when population growth is high. Of the three questing tick life stages (larvae, nymphs, and adults), nymphs are most often associated with transmitting the bacteria to humans, and previous work suggests a mix of abiotic and biotic drivers are associated with nymph abundance. However, understanding tick population growth requires understanding mortality and transition probabilities for each stage and each stage may be individually and uniquely impacted by climate and host availability. A larval tick, for example, may experience warming temperatures differently than nymph or adults, because they are present on the landscape at different times. Here, we describe and validate a model that accounts for field sampling design and evaluates abiotic (temperature, relative humidity, precipitation) and biotic (host abundance) drivers of variation in tick population growth. To account for the drivers of subseasonal and interannual variability in demography, phenology, and population density, we built stage‐structured population models that account for variability in meteorology and host population abundance throughout the full tick lifecycle. Our model is fit and validated with 11 years of tick and host data from the northeastern United States. In this context, we found that a four‐stage model that includes unique transitions to and from a dormant, overwintering nymph state outperforms a model that only includes the three questing stages, and that incorporating the abundance of the predominant host species, Peromyscus leucopus, and weather variables improved predictions and model fit. Additionally, the model accurately predicted all three questing stages at sites different than where they were calibrated, showing that this model structure is generally transferable. Overall, this model lays a foundation for the real‐time iterative forecasting of tick populations needed to effectively protect public health. [ABSTRACT FROM AUTHOR]

The European red squirrel (Sciurus vulgaris) is a common host for Ixodes ricinus ticks in urban and rural habitats, however, studies on ticks and tick-borne pathogens (TBPs) of squirrels have not been conducted in Poland yet. Thus, the aims of the current study were to assess and compare the prevalence and abundance of ticks on red squirrels trapped at two sites in the Warsaw area (in an urban forest reserve and an urban park) and using molecular tools, to assess the genetic diversity of three pathogens (Borrelia burgdorferi sensu lato, Rickettsia and Babesia spp.) in I. ricinus ticks collected from squirrels. For the detection of Rickettsia spp. a 750 bp long fragment of the citrate synthase gltA gene was amplified; for B. burgdorferi s.l. 132f/905r and 220f/824r primers were used to amplify the bacterial flaB gene fragments (774 and 605 bp, respectively) and for Babesia spp., a 550 bpfragment of 18S rRNA gene was amplified. In total, 91 red squirrels were examined for ticks. There were differences in tick prevalence and mean abundance of infestation in squirrels from the urban forest reserve and urban park. Three species of B. burgdorferi s.l., Rickettsia spp., and Babesia microti were detected in ticks removed from the squirrels. Our results broaden knowledge of S. vulgaris as an important host for immature I. ricinus stages and support the hypothesis that red squirrels act as a reservoir of B. burgdorferi. Moreover, we conclude that red squirrels may also play a role in facilitating the circulation of other pathogens causing serious risk of tick-borne diseases in natural and urban areas. [ABSTRACT FROM AUTHOR]

Borrelia burgdorferi's inosine-5′-monophosphate dehydrogenase (IMPDH, GuaB encoded by the guaB gene) is a potential therapeutic target. GuaB is necessary for B. burgdorferi replication in mammalian hosts but not in standard laboratory culture conditions. Therefore, we cannot test novel GuaB inhibitors against B. burgdorferi without utilizing mammalian infection models. This study aimed to evaluate modifications to a standard growth medium that may mimic mammalian conditions and induce the requirement of GuaB usage for replication. The effects of two GuaB inhibitors (mycophenolic acid, 6-chloropurine riboside at 125 μM and 250 μM) were assessed against B. burgdorferi (guaB+) grown in standard Barbour–Stoenner–Kelly-II (BSK-II) medium (6% rabbit serum) and BSK-II modified to 60% concentration rabbit serum (BSK-II/60% serum). BSK-II directly supplemented with adenine, hypoxanthine, and nicotinamide (75 μM each, BSK-II/AHN) was also considered as a comparison group. In standard BSK-II, neither mycophenolic acid nor 6-chloropurine riboside affected B. burgdorferi growth. Based on an ANOVA, a dose-dependent increase in drug effects was observed in the modified growth conditions (F = 4.471, p = 0.001). Considering higher drug concentrations at exponential growth, mycophenolic acid at 250 μM reduced spirochete replication by 48% in BSK-II/60% serum and by 50% in BSK-II/AHN (p < 0.001 each). 6-chloropurine riboside was more effective in both mediums than mycophenolic acid, reducing replication by 64% in BSK-II/60% serum and 65% in BSK-II/AHN (p < 0.001 each). These results demonstrate that modifying BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces the effects of GuaB inhibitors. This represents the first use of GuaB inhibitors against Borrelia burgdorferi, building on tests against purified B. burgdorferi GuaB. The strong effects of 6-chloropurine riboside indicate that B. burgdorferi can salvage and phosphorylate these purine derivative analogs. Therefore, this type of molecule may be considered for future drug development. Optimization of this culture system will allow for better assessment of novel Borrelia-specific GuaB inhibitor molecules for Lyme disease interventions. The use of GuaB inhibitors as broadcast sprays or feed baits should also be evaluated to reduce spirochete load in competent reservoir hosts. [ABSTRACT FROM AUTHOR]

Lyme disease is the most prevalent tick-borne infection caused by Borrelia burgdorferi bacteria in North America. Other Borrelia species are predominately the cause of this disease in Eurasia with some distinct and various overlapping manifestations. Consequently, caution must be exercised when comparing the disease and its manifestations and treatment regimens in North America and Europe. Diagnosis of the early Lyme disease remains difficult using the currently FDA approved serological tests in the absence of a reported tick bite or of erythema migrans in many individuals, non-specific initial symptoms, and the absence of detectable anti-Borrelia antibodies in the prepatent period of infection. Furthermore, it is difficult to distinguish persistence of infection and disease versus reinfection in the endemic regions of Lyme disease by serological assays. If early infection remains untreated, spirochetes can disseminate and could affect various organs in the body with a variety of disease manifestations including arthralgias and musculoskeletal pain, neurologic symptoms and anomalies, and acrodermatitis chronicum atrophicans (ACA) in Europe. Although most patients recover after antibiotic treatment, an estimated ~10-20% patients in the United States show persistence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). The causes and biomarkers of PTLDS are not well-defined; however, several contributing factors with inconsistent degree of supporting evidence have been suggested. These include antigenic debris, dysregulation of immunological response, bacterial persisters, or combination of these features. This review highlights currently employed treatment approaches describing different antimicrobials used, and vaccine candidates tried to prevent B. burgdorferi infection. [ABSTRACT FROM AUTHOR]

ABSTRACT In Borrelia burgdorferi, BB0556 was annotated as a conserved hypothetical protein. We herein investigated gene expression and the importance of this protein during infection. Our data support that bb0556 forms an operon with five other genes. A transcriptional start site and the associated σ70‐type promoter were identified in the sequences upstream of bb0554, and luciferase reporter assays indicated that this promoter is functional in B. burgdorferi. Furthermore, the sequences upstream of bb0556 contain an internal promoter to drive gene expression. bb0556 expression was affected by various environmental factors such as changes in temperature, pH, and cell density when B. burgdorferi was grown in vitro. Surprisingly, significant differences were observed for bb0556 expression between B. burgdorferi strains B31‐A3 and CE162, likely due to the different cis‐ and trans‐acting factors in these strains. Moreover, bb0556 was found to be highly expressed by B. burgdorferi in infected mice tissues, suggesting that this gene plays an important role during animal infection. To test this hypothesis, we generated a bb0556 deletion mutant in a virulent bioluminescent B. burgdorferi strain. The mutant grew normally in the medium and displayed no defect in the resistance to environmental stresses such as reactive oxygen species, reactive nitrogen species, and osmotic stress. However, when the infectivity was compared between the mutant and its parental strain using in vivo bioluminescence imaging as well as analyses of spirochete recovery and bacterial burdens in animal tissues, our data showed that, contrary to the parental strain, the mutant was unable to infect mice. Complementation of bb0556 in cis fully restored the infectious phenotype to wild‐type levels. Taken together, our study demonstrates that the hypothetical protein BB0556 is a novel virulence factor essential for B. burgdorferi mammalian infection. [ABSTRACT FROM AUTHOR]

Background: Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. Although public health surveillance for LB has been conducted in Romania since 2007, the extent of under-detection of Bbsl infections by LB surveillance has not been estimated. We therefore estimated the under-detection of symptomatic Bbsl infections by LB surveillance to better understand the LB burden in Romania. Methods: The number of incident symptomatic Bbsl infections were estimated from a seroprevalence study conducted in six counties (population 2.3 M) and estimates of the symptomatic proportion and duration of persistence of anti-Bbsl immunoglobulin G (IgG) antibodies. The number of incident symptomatic Bbsl infections were compared with the number of surveillance-reported LB cases to derive an under-detection multiplier, and then the under-detection multiplier was applied to LB surveillance data to estimate the incidence of symptomatic Bbsl infection from 2018 to 2023. Results: We estimate that there were 1968 individuals with incident symptomatic Bbsl infection in the six counties where the seroprevalence study was conducted in 2020, compared with the 187 surveillance-reported LB cases, resulting in an under-detection multiplier of 10.5 (i.e., for every surveillance-reported LB case, there were 10.5 symptomatic incident Bbsl infections). The incidence of symptomatic Bbsl infection in the six counties was 86.9/100,000 population in 2023, similar to the incidence in 2018−2020 (86.0) and higher than in 2021−2022 (40.3). Conclusions: There is a higher incidence of symptomatic Bbsl infection than is reported through public health surveillance for LB in Romania. Additional efforts are needed to strengthen disease prevention and address the important public health problem of LB. [ABSTRACT FROM AUTHOR]

Background: Ticks carry a variety of microorganisms, some of which are pathogenic to humans. The human risk of tick-borne diseases depends on, among others, the prevalence of pathogens in ticks biting humans. To follow-up on this prevalence over time, a Belgian study from 2017 was repeated in 2021. Methods: During the tick season 2021, citizens were invited to have ticks removed from their skin, send them and fill in a short questionnaire on an existing citizen science platform for the notification of tick bites (TekenNet). Ticks were morphologically identified to species and life stage level and screened using multiplex qPCR targeting, among others, Borrelia burgdorferi (sensu lato), Anaplasma phagocytophilum, Borrelia miyamotoi, Neoehrlichia mikurensis, Babesia spp., Rickettsia helvetica and tick-borne encephalitis virus (TBEV). The same methodology as in 2017 was used. Results: In 2021, the same tick species as in 2017 were identified in similar proportions; of 1094 ticks, 98.7% were Ixodes ricinus, 0.8% Ixodes hexagonus and 0.5% Dermacentor reticulatus. A total of 928 nymphs and adults could be screened for the presence of pathogens. Borrelia burgdorferi (s.l.) was detected in 9.9% (95% CI 8.2–12.0%), which is significantly lower than the prevalence of 13.9% (95% CI 12.2–15.7%) in 2017 (P = 0.004). The prevalences of A. phagocytophilum (4.7%; 95% CI 3.5–6.3%) and R. helvetica (13.3%; 95% CI 11.2–15.6%) in 2021 were significantly higher compared to 2017 (1.8%; 95% CI 1.3–2.7% and 6.8%; 95% CI 5.6–8.2% respectively) (P < 0.001 for both). For the other pathogens tested, no statistical differences compared to 2017 were found, with prevalences ranging between 1.5 and 2.9% in 2021. Rickettsia raoultii was again found in D. reticulatus ticks (n = 3/5 in 2021). Similar to 2017, no TBEV was detected in the ticks. Co-infections were found in 5.1% of ticks. When combining co-infection occurrence in 2017 and 2021, a positive correlation was observed between B. burgdorferi (s.l.) and N. mikurensis and B. burgdorferi (s.l.) and B. miyamotoi (P < 0.001 for both). Conclusions: Although the 2021 prevalences fell within expectations, differences were found compared to 2017. Further research to understand the explanations behind these differences is needed. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion We aimed to investigate the causes of acute peripheral facial palsy (PFP) in Danish children and to explore whether neuroborreliosis‐related PFP could be diagnosed without lumbar puncture using clinical symptoms and serum Borrelia burgdorferi (Bb) antibodies.This retrospective population‐based cohort study included children undergoing lumbar puncture for PFP between 2019 and 2023 in Denmark's Capital Region. Diagnostic performance measures for neuroborreliosis‐related PFP were compared between serum Bb IgG alone and clinical risk scores combining Bb IgG with clinical parameters.Of the 326 patients with PFP, 137 (42%) were diagnosed with neuroborreliosis and 151 (46%) had Bell's palsy. Positive predictive value for serum Bb IgG alone was 88% (95% CI 79–93) and negative predictive value was 83% (95% CI 75–88). The positive predictive value of a risk score with seven additional parameters was 90% (95% CI 81–95) and negative predictive value 87% (95% CI 80–92).The positive predictive value of serum Bb IgG alone was high in our setting, where nearly half of children with PFP had neuroborreliosis. In high endemic settings, lumbar punctures may be reduced by (i) treating all children with PFP with doxycycline or (ii) treating Bb IgG positive children and performing lumbar puncture in seronegative children. [ABSTRACT FROM AUTHOR]

Tick-borne infections are increasing in the United States and around the world. The most common tick-borne disease in the United States is Lyme disease caused by infection with the spirochete Borrelia burgdorferi (Bb), and pathogenesis varies from subclinical to severe. Bb infection is transmitted by Ixodes ticks, which can carry multiple other microbial pathogens, including Ehrlichia species. To address how the simultaneous inoculation of a distinct pathogen impacted the course of Bb-induced disease, we used C57BL/6 (B6) mice which are susceptible to Bb infection but develop only mild joint pathology. While infection of B6 mice with Bb alone resulted in minimal inflammatory responses, mice co-infected with both Bb and the obligate intracellular pathogen Ehrlichia muris (Em) displayed hematologic changes, inflammatory cytokine production, and emergency myelopoiesis similar to what was observed in mice infected only with Em. Moreover, infection of B6 mice with Bb alone resulted in no detectable joint inflammation, whereas mice co-infected with both Em and Bb exhibited significant inflammation of the ankle joint. Our findings support the concept that co-infection with Ehrlichia can exacerbate inflammation, resulting in more severe Bb-induced disease. [ABSTRACT FROM AUTHOR]

Tick-borne pathogen emergence is dependent on the abundance and distribution of competent hosts in the environment. Ixodes scapularis ticks are generalist feeders, and their pathogen infection prevalence depends on their relative feeding on local competent and non-competent hosts. The ability to determine what host a larval life stage tick fed on can help predict infection prevalence, emergence, and spread of certain tick-borne pathogens and the risks posed to public health. Here, we use a newly developed genomic target-based technique to detect the source of larval bloodmeals by sampling questing nymphs from Block Island, RI, a small island with a depauperate mammalian community. We used previously designed specific assays to target all known hosts on this island and analyzed ticks for four human pathogenic tick-borne pathogens. We determined the highest proportion of larvae fed on avian species (42.34%), whitefooted mice (36.94%), and white-tailed deer (20.72%) and occasionally fed on feral cats, rats, and voles, which are in low abundance on Block Island. Additionally, larvae that had fed on white-footed mice were significantly more likely to be infected with Borrelia burgdorferi and Babesia microti, while larvae that had fed on white-footed mice or white-tailed deer were significantly more likely to be infected with, respectively, mouseand deer-associated genotypes of Anaplasma phagocytophilum. The ability to detect a nymph's larval host allows for a better understanding of tick feeding behavior, host distribution, pathogen prevalence, and zoonotic risks to humans, which can contribute to better tick management strategies. [ABSTRACT FROM AUTHOR]

Lyme disease, the leading vector-borne ailment in the U.S., annually affects an estimated 476,000 individuals, predominantly in the Northeast and Upper Midwest. Despite its increasing incidence, the evaluation of risk within U.S. cities, including natural public lands, remains inadequate. This study focuses on blacklegged tick occurrences and Borrelia burgdorferi infection prevalence in 24 Staten Island parks, aiming to assess Lyme disease exposure risk. Monthly acarological risk index (ARI) calculations from 2019 to 2022 revealed elevated values (0.16–0.53) in specific parks, notably Wolfe's Pond Park, High Rock Park, Clay Pit Pond Park, Clove Lake Park, and Fair View Park. June (0.36) and November (0.21) consistently exhibited heightened ARIs, aligning with peak tick collection months. Despite stable yearly infection rates at 28.97%, tick densities varied significantly between parks and years. Identifying a high transmission risk in specific parks in Staten Island, a highly urbanized part of New York City, emphasizes the continuous necessity for Lyme disease risk management, even within the greenspaces of large cities. [ABSTRACT FROM AUTHOR]

Background Vaccine candidate VLA15 is designed to protect against the dominant Borrelia genospecies-causing Lyme disease in North America and Europe. Active immunization with VLA15 has protected in the mouse model of tick challenge. VLA15 is currently under evaluation in clinical studies for the prevention of Lyme borreliosis. Methods Mice were passively administered sera from clinical trial participants vaccinated with VLA15, or normal human serum from unvaccinated individuals as control. Posttransfer serum anti-outer surface protein A (OspA) immunoglobulin G titers were assessed by enzyme-linked immunosorbent assay. Following passive transfer, mice were challenged with Ixodes ticks colonized with Borrelia burgdorferi (OspA serotype 1) or Borrelia afzelii (OspA serotype 2) and infection was determined by serology for VlsE C6 or by polymerase chain reaction and culture to assess the presence of Borrelia bacteria. Results Passive transfer of immune sera prevented transmission of Borrelia from the tick vector and protected mice against challenge. Posttransfer protective threshold immunoglobulin G antibody titers were observed in this animal model of 131 U/mL for B burgdorferi (OspA serotype 1) and 352 U/mL for B afzelii (serotype 2). Conclusions Passive transfer of sera from trial participants immunized with VLA15 protected mice from borreliosis in a tick challenge model. This indicates that VLA15 induces functional immune responses in people that can be linked to efficacy in a stringent preclinical model. [ABSTRACT FROM AUTHOR]

Background: IL-26 has demonstrated antimicrobial properties, as well as in the degradation of DNA from the Lyme disease spirochete Borrelia burgdorferi (Bb). Additionally, IL-26 can promote macrophage activation and enhance Bb phagocytotic activity. It is unclear if cell-mediated immune responses are modulated through TLR9 signaling when exposed to IL-26 Bb DNA complexes in post-treatment Lyme disease syndrome (PTLDS). Objective: We here aim to explore the effect of IL-26 in human Toll-like receptor (TLR)-9's activation upon the recognition of Bb DNA. Methods: We utilized a single-receptor cell system, HEK-Dual™ hTLR9 cells, which harbors two reporter plasmids for the NF-κB and IL-8 signaling pathways. Bb DNA was exposed to increasing concentrations of IL-26 in monomeric or dimeric form and then used to stimulate the cells for 4 h. The TLR-9 ligand CpG was used as a control. Results: We observed that NF-κB and IL-8 activation was maximal when the cells were stimulated with Bb DNA that had been treated with 5 µM of IL-26 monomer and 1 µM of IL-26 dimer. The same was observed for IL-8 activation upon CpG stimulation. We observed, however, a decrease in NF-κB activation when treated with either form of IL-26. An NF-κB activation increase did not occur with IL-26-treated TLR9 ligand CpG. Conclusions: Our study shows an enhancement in NF-κB and IL-8 activation upon the recognition of IL-26-treated Bb DNA by TLR9, which suggests an increase in sensing by the TLR9 of Bb DNA when it is in the form of an IL-26-Bb DNA complex. These findings will prompt further studies on the interaction between IL-26 and Bb DNA. [ABSTRACT FROM AUTHOR]

The presence of Borrelia burgdorferi sensu lato (the agent of Lyme disease) in Ixodes ricinus ticks removed from wild birds and questing ticks was investigated. A total of 345 ticks from 75 infested birds belonging to 10 species and 274 questing ticks collected from the surrounding vegetation were examined by PCR for Borrelia burgdorferi s. l. Pathogen DNA was found in 8.1% (28/345) of the bird-feeding ticks - 10.9% (11/101) in larvae and 7.0% (17/244) in nymphs. Prevalence of infection was 9.4% in ticks from the Eurasian blackbird (Turdus merula), 4.0% in ticks from the song thrush (T. philomelos) and 16.6% from the European robin (Erithacus rubecula). Detection of infected larvae (13.3%) collected from the Eurasian blackbird suggests that this species might contribute to the transmission to the vector I. ricinus. The overall prevalence of B. burgdorferi in the questing nymphs was 10.6%. This is the first report of B. burgdorferi s. l. infection in I. ricinus from wild birds in Bulgaria. [ABSTRACT FROM AUTHOR]

Borrelia burgdorferi sensu lato complex comprises 20 species, from which B. afzelii, B. garinii, B. burgdorferi sensu stricto, B. bavariensis, and B. spielmanii are directly associated with Lyme borreliosis, while B. bissettiae, B. lusitaniae, and B. valaisiana were detected in individual cases. Their main vector in Europe is the hard tick species Ixodes ricinus. To date, two species, B. spielmanii and B. lusitaniae, have been molecularly detected in Bosnia and Herzegovina. To test for the presence of other Borrelia species, we performed nested PCR targeting intergenic region rrf (5S) – rrl (23S) on DNA isolates from 49 ticks collected from vegetation by flagging method and 43 removed from humans in The Center for Emergency Medical Assistance of the Sarajevo Canton and The Healthcare Centers of the Sarajevo Canton. Borrelia species were detected by one-directional Sanger sequencing of the amplified region using the same forward primer as in PCR. Out of six Borrelia species detected in the present study, this is the first record of B. afzelii, B. garinii, B. burgdorferi s.s. B. bavariensis, and B. valaisiana in Bosnia and Herzegovina. [ABSTRACT FROM AUTHOR]

Lyme borreliosis (LB), a tick-borne infection caused by bacteria in the Borrelia burgdorferi sensu lato complex, is increasingly prevalent on the Balkan Peninsula, including Bulgaria, where it is the most common tick-borne disease. This study aimed to assess the seroprevalence of LB across Bulgaria by analyzing 1892 serum samples for specific IgG antibodies using a two-tier testing protocol involving an ELISA and immunoblot methods. The results revealed an overall seroprevalence rate of 5.4%, with significant variation based on age, sex, and residence. Seroprevalence increased with age, peaking at 8.4% in individuals over 65 years. Males had a seroprevalence of 8.4% compared to 3.3% in females, and rural residents showed higher seroprevalence (10.2%) compared to urban residents (4.4%). Regional analysis indicated that seroprevalence ranged from 0.0% to 20.0%, with higher rates in northern provinces such as Gabrovo (18.9%) and Targovishte (20.0%). This study highlights the importance of two-step testing protocols for accurate diagnosis and underscores the need for increased awareness and further research to enhance public health measures and the management of LB in Bulgaria. [ABSTRACT FROM AUTHOR]

Five chromosomally encoded proteins, BB0108, BB0126, BB0298, BB0323, and BB0689, from Borrelia burgdorferi sensu lato (s.l.), were obtained in three variants each, representing the most common genospecies found in Europe (Borrelia afzelii, Borrelia burgdorferi sensu stricto (s.s.), and Borrelia garinii). The reactivity of these recombinant proteins with the IgM and IgG antibodies present in human serum was assessed using Western blot (WB) and the ELISA. In IgG-WB, the proteins exhibited varying reactivity, peaking at approximately 40–50% for BB0108 and BB0689. However, none of these proteins were recognized by specific antibodies in the IgM-WB. The sensitivity of IgG-ELISA based on three variants of BB0108 and BB0323 ranged from 71% to 82% and from 62% to 72%, respectively. Conversely, the specificity of both tested proteins was consistently above 82%. Tests utilizing single variants of BB0323 did not yield any diagnostic value in detecting IgM antibodies. However, BB0108 demonstrated recognition by antibodies present in 52% to 63% of the tested sera. These antigens appear advantageous due to the consistent reactivity observed across their variants. This observation suggests that appropriate selection of antigens conserved within B. burgdorferi s.l. could offer a solution to the issue of variable sensitivity encountered in serodiagnostic tests across Europe. [ABSTRACT FROM AUTHOR]

Lyme disease is the most commonly reported vector-borne disease in the United States. Bartonella constitute an additional zoonotic pathogen whose public health impact and diversity continue to emerge. Rapid, sensitive, and specific detection of these and other vector-borne pathogens remains challenging, especially for patients with persistent infections. This report describes an approach for DNA extraction and PCR testing for the detection of Bartonella spp. and Borreliella spp. from dry blood spot (DBS) specimens from human patients. The present study included extraction of DNA and PCR testing of DBS samples from 105 patients with poorly defined, chronic symptoms labeled as Lyme-Like Syndromic Illness (LLSI). Bartonella spp. DNA was detected in 20/105 (19%) and Borreliella spp. DNA was detected in 41/105 (39%) patients with LLSI. Neither group of organisms was detected in DBS samples from 42 healthy control subjects. Bartonella spp. 16S–23S rRNA internal transcribed spacer sequences were highly similar to ones previously identified in yellow flies, lone star ticks, a human patient from Florida, mosquitoes in Europe, or B. apihabitans and choladocola strains from honeybees. These human strains may represent new genetic strains or groups of human pathogenic species of Bartonella. The 41 Borreliella spp. flaB gene sequences obtained from human patients suggested the presence of four different species, including B. burgdorferi, B. americana, B. andersonii, and B. bissettiae/carolinensis-like strains. These results suggest that specific aspects of the DBS DNA extraction and PCR approach enabled the detection of Bartonella spp. and Borreliella spp. DNA from very small amounts of human whole blood from some patients, including specimens stored on filter paper for 17 years. [ABSTRACT FROM AUTHOR]

This study reveals a significant presence of ticks and tick-borne pathogens in urban recreational areas of Tallinn, Estonia. During the period of May–June 2018, 815 Ixodes ticks were collected from an area of 11,200 m2 using the flagging method. Tick density reached up to 18.8 ticks per 100 m2, indicating a high concentration of ticks in these urban green spaces. Pathogen analysis demonstrated that 34% of the collected ticks were infected with at least one pathogen. Specifically, Borrelia burgdorferi s.l., the causative agent of Lyme borreliosis, was detected in 17.4% of the ticks; Rickettsia spp. was detected in 13.5%; Neoehrlichia mikurensis was detected in 5.5%; Borrelia miyamotoi was detected in 2.6%; and Anaplasma phagocytophilum and tick-borne encephalitis virus were detected in 0.5% each. These findings indicate that the prevalence and abundance of ticks and tick-borne pathogens in these urban environments are comparable to or even exceed those observed in natural endemic areas. Given the increasing incidence of Lyme borreliosis in Central and Northern Europe, the risk of tick bites and subsequent infection in urban recreational sites should not be underestimated. Public health measures, including enhanced awareness and precautionary information, are essential to mitigate the risk of tick-borne diseases in these urban settings. [ABSTRACT FROM AUTHOR]

Borrelia burgdorferi, the bacterium responsible for Lyme disease, has been shown to form antimicrobial-tolerant biofilms, which protect it from unfavorable conditions. Bacterial biofilms are known to significantly contribute to severe inflammation, such as carditis, a common manifestation of Lyme disease. However, the role of B. burgdorferi biofilms in the development of Lyme carditis has not been thoroughly investigated due to the absence of an appropriate model system. In this study, we examined heart tissues from mice infected with B. burgdorferi for the presence of biofilms and inflammatory markers using immunohistochemistry (IHC), combined fluorescence in situ hybridization FISH/IHC, 3D microscopy, and atomic force microscopy techniques. Our results reveal that B. burgdorferi spirochetes form aggregates with a known biofilm marker (alginate) in mouse heart tissues. Furthermore, these biofilms induce inflammation, as indicated by elevated levels of murine C-reactive protein near the biofilms. This research provides evidence that B. burgdorferi can form biofilms in mouse heart tissue and trigger inflammatory processes, suggesting that the mouse model is a valuable tool for future studies on B. burgdorferi biofilms. [ABSTRACT FROM AUTHOR]

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We evaluated spatial-temporal risk for Lyme disease in northwestern North Carolina, USA, by using individual-level canine Borrelia burgdorferi seroprevalence data collected during 2017–2021 at routine veterinary screenings for tickborne diseases. Seroprevalence in dogs increased from 2.2% (47/2,130) in 2017 to 11.2% (339/3,033) in 2021. The percentage of incident seropositivity increased from 2.1% (45/2,130) in 2017 to 7.6% (231/3,033) in 2021. Exploratory geographic analyses found canine seroprevalence shifted from clustered (2017, Moran’s I = 0.30) to dispersed (2021, Moran’s I = −0.20). Elevation, slope, aspect, and forest land cover density were associated with canine seroprevalence within various household buffer regions in 2017. Slope was associated with seroprevalence at the household level in 2021. Results support the use of individual-level canine seroprevalence data for monitoring human risk for Lyme disease. Establishing sentinel veterinary clinics within Lyme disease–emergent communities might promote prevention and control efforts and provide opportunities for educational and behavioral interventions.

We investigated differences in risk factors and preventive behaviors by age and sex among persons with reported Lyme disease in Ontario, Canada, during 2015–2022. Incidence rates peaked among children 5–9 and adults 50–79 years of age. Median age was higher for female than male case-patients (54 vs. 51 years). Male case-patients reported more activity in wooded and tall grass areas than did female case-patients; fewer male case-patients reported sharing living space with outdoor-exposed companion animals. As age increased, more case-patients reported activity in blacklegged tick habitats, exposure to ticks, and wearing adequate clothing, but fewer reported sharing living space with outdoor-exposed companion animals. Adoption of preventive behaviors was relatively low and did not differ by sex. Male case-patients, children 5–9 years of age and their parents or caregivers, and adults >59 years of age represent populations that would benefit from tailored public health messaging on Lyme disease prevention.

Background & objectives: Lyme disease is a multisystemic disease caused by the bacteria in the Borrelia burgdorferi sensu lato complex, which is transmitted by ticks of the Ixodes genus. Although there are seroprevalence studies and case reports of Lyme disease from various regions in Turkey, there is no widespread epidemiological research. This study aimed to determine the frequency of Lyme disease in the cases followed-up after tick contact and to examine the isolated ticks to reveal tick population from Bolu province. Methods: In this study, cases who applied to the emergency department due to tick contact between April and September 2020 were firstly evaluated in our infectious diseases and clinical microbiology outpatient clinic on the third day of exposure and antibodies against Lyme disease were investigated with the IFA method to exclude the patients who were previously exposed to B. burgdorferi. Thereafter, patients were requested to continue outpatient visits at the 1st and 3rd month control. At these controls, serum samples were taken to study B.burgdorferi antibodies with the ELISA method which were stored at - 20°C until the study day. Results: Out of 123 patients who came to first control, 69 patients continued later to at least one of the two controls (either at first or third month). Of these 69 patients, only one (1.4%) was diagnosed with Lyme borreliosis according to clinical and laboratory features. Erythema migrans did not occur in any of the cases. Serum samples were assessed by ELISA method. Asymptomatic infection was detected in 22 cases (30.5%). In addition, we could obtain 46 ticks from our cases and two genera were identified. Forty-two (91.3%) were Ixodes spp., and two (4.3%) were Hyalomma spp. Interpretation & conclusion: In this study, which was carried out for the first time in the province of Bolu, it was concluded that the cases presenting with a history of tick contact were most frequently exposed to Ixodes spp ticks, and the probability of developing Lyme borreliosis was low (1,4%) during the three-month follow-up period. Further studies with more number of cases and more extended follow-up period are needed.

Background: IL-26 has demonstrated antimicrobial properties, as well as in the degradation of DNA from the Lyme disease spirochete Borrelia burgdorferi (Bb). Additionally, IL-26 can promote macrophage activation and enhance Bb phagocytotic activity. It is unclear if cell-mediated immune responses are modulated through TLR9 signaling when exposed to IL-26 Bb DNA complexes in post-treatment Lyme disease syndrome (PTLDS). Objective: We here aim to explore the effect of IL-26 in human Toll-like receptor (TLR)-9’s activation upon the recognition of Bb DNA. Methods: We utilized a single-receptor cell system, HEK-Dual™ hTLR9 cells, which harbors two reporter plasmids for the NF-κB and IL-8 signaling pathways. Bb DNA was exposed to increasing concentrations of IL-26 in monomeric or dimeric form and then used to stimulate the cells for 4 h. The TLR-9 ligand CpG was used as a control. Results: We observed that NF-κB and IL-8 activation was maximal when the cells were stimulated with Bb DNA that had been treated with 5 µM of IL-26 monomer and 1 µM of IL-26 dimer. The same was observed for IL-8 activation upon CpG stimulation. We observed, however, a decrease in NF-κB activation when treated with either form of IL-26. An NF-κB activation increase did not occur with IL-26-treated TLR9 ligand CpG. Conclusions: Our study shows an enhancement in NF-κB and IL-8 activation upon the recognition of IL-26-treated Bb DNA by TLR9, which suggests an increase in sensing by the TLR9 of Bb DNA when it is in the form of an IL-26-Bb DNA complex. These findings will prompt further studies on the interaction between IL-26 and Bb DNA.

Lyme disease is the leading tick-borne infection in the United States, caused by the pathogenic spirochete Borreliella burgdorferi, formerly known as Borrelia burgdorferi. Diderms, or bacteria with dual-membrane ultrastructure, such as B. burgdorferi, have multiple methods of transporting and integrating outer membrane proteins (OMPs). Most integral OMPs are transported through the β-barrel assembly machine (BAM) complex. This complex consists of the channel-forming OMP BamA and accessory lipoproteins that interact with the five periplasmic, polypeptide transport-associated (POTRA) domains of BamA. Another system, the translocation and assembly module (TAM) system, has also been implicated in OMP assembly and export. The TAM system consists of two proteins, the BamA paralog TamA which has three POTRA domains and the inner membrane protein TamB. TamB is characterized by a C-terminal DUF490 domain that interacts with the POTRA domains of TamA. Interestingly, while TamB is found in almost all diderms, including B. burgdorferi, TamA is found almost exclusively in Proteobacteria. This strongly suggests a TamA-independent role of TamB in most diderms. We previously demonstrated that BamA interacts with TamB in B. burgdorferi and hypothesized that this is facilitated by the BamA POTRA domains interacting with the TamB DUF490 domain. In this study, we utilized protein-protein co-purification assays to empirically demonstrate that the B. burgdorferi TamB DUF490 domain interacts with BamA POTRA2 and POTRA3. We also observed that the DUF490 domain of TamB interacts with the accessory lipoprotein BamB. To examine if the BamA-TamB interaction is more ubiquitous among diderms, we examined BamA-TamB interactions in Salmonella enterica serovar Typhimurium (St). Interestingly, even though St encodes a TamA protein that interacts with TamB, we observed that the TamB DUF490 of St interacts with BamA in this organism. Our combined findings strongly suggest that the TamB-BamA interaction occurs independent of the TamA component of the TAM protein export system. [ABSTRACT FROM AUTHOR]

Introduction: The Maximum Entropy models (MaxEnt) is commonly employed for early detection of disease transmission, particularly effective in assessing the risk zones and intensity of tick-borne disease transmission based on climatic factors. Methods: Utilizing the diversity data of common ticks in Qinghai, along with surveillance statistics tick-borne pathogens of ticks and epidemiological information, we have charted and predicted the prevalence of tick and tickborne pathogens across Qinghai province. Results and Discussion: The findings indicate that the pivotal environmental factors influencing the distribution of ticks and tick-borne pathogens include land use and land cover (Lucc), elevation (Elev), annual precipitation (Bio12) and annual mean temperature (Bio1). Notably, for Dermacentor nuttalli, the significant environmental factors accounted for 35.2% for Lucc, 24.7% for Elev and 18.6% for Bio12. In the case of Dermacentor silvaru, the pivotal factors contributed 33.2% for Lucc, 23.7% for Elev and 22.6% for Bio1. For Haemaphysalis qinghaiensis, the key environmental variables were 45% for Elev, 30.9% for Lucc and 18.4% for Bio12. Regarding the pathogens, the environmental factors influencing Borrelia burgdorferi contributed 61.5% for Lucc, 13.3% for Elev and 11.9% for Bio1. For Piroplasmida, the contribution was 62.1% for Lucc, 16.7% for Bio1 and 9.9% for Bio12. Rickettsia was influenced by factors accounting for 34.2% for Lucc, 29.7% for Elev and 17.3% for Bio12, while Anaplasma variables contributed 38.2% for Bio1, 26.6% for Lucc and 18.9% for Bio12. The finding indicated that the three predominantly ticks species (D. nuttalli, D. silvaru, and H. qinghaiensis) and the primary tick-borne pathogens (B. burgdorferi, Piroplasmida, Rickettsia, and Anaplasma) are predominantly concentrated in the source regions of the Yellow River, the Yangtze River, the Lancang River, and the eastern part of the Haixi Autonomous Prefecture. Projected under the ssp245 scenario, there is a notable expansion trend in the risk areas for ticks and tick-borne pathogens These findings are consistent with previous epidemiological studies on major ticks and tick-borne diseases in Qinghai conducted by our laboratory, this suggests the feasibility of using the MaxEnt model to predict the distribution of tick-borne disease transmission and compensates for the paucity of research on the Maxent model in the Qinghai Province. [ABSTRACT FROM AUTHOR]

Recent changes in climate and human land‐use have resulted in alterations of the geographic range of many species, including human pathogens. Geographic range expansion and population growth of human pathogens increase human disease risk. Relatively little empirical work has investigated the impact of range changes on within‐population variability, a contributor to both colonization success and adaptive potential, during the precise time in which populations are colonized. This is likely due to the difficulties of collecting appropriate natural samples during the dynamic phase of migration and colonization. We systematically collected blacklegged ticks (Ixodes scapularis) across New York State (NY), USA, between 2006 and 2019, a time period coinciding with a rapid range expansion of ticks and their associated pathogens including Borrelia burgdorferi, the etiological agent of Lyme disease. These samples provide a unique opportunity to investigate the population dynamics of human pathogens as they expand into novel territory. We observed that founder effects were short‐lived, as gene flow from long‐established populations brought almost all B. burgdorferi lineages to newly colonized populations within just a few years of colonization. By 7 years post‐colonization, B. burgdorferi lineage frequency distributions were indistinguishable from long‐established sites, indicating that local B. burgdorferi populations experience similar selective pressures despite geographic separation. The B. burgdorferi lineage dynamics elucidate the processes underlying the range expansion and demonstrate that migration into, and selection within, newly colonized sites operate on different time scales. [ABSTRACT FROM AUTHOR]

Background During infection with the Lyme arthritis (LA) pathogen Borrelia burgdorferi , T-cell responses to both host and pathogen are dysregulated, resulting in chronic infection and frequent development of autoimmunity. Methods To assess CD4+ T-cell epitopes presented during development of LA, we used an unbiased, immunopeptidomics approach to characterize the major histocompatibility complex (MHC) class II immunopeptidome in B burgdorferi -infected C57BL/6 (B6) mice, which develop mild, self-limiting LA, and infected B6 Il10 −/− mice, which develop severe, persistent LA at 0, 4, and 16 weeks postinfection (22–23 mice per group). Results Peptides derived from proteins involved in adaptive T- and B-cell responses and cholesterol metabolism, including human Lyme autoantigen apolipoprotein B-100 (apoB-100), were enriched in infected Il10−/− mice; whereas peptides derived from proteins involved in neutrophil extracellular net formation were enriched in infected B6 mice. Presentation of apoB-100 peptides showed evidence of epitope expansion during infection. Of several identified B burgdorferi peptides, only 1, a methyl-accepting chemotaxis protein peptide Mcp4442–462, was immunogenic. Conclusions ApoB-100, a human Lyme autoantigen, undergoes marked epitope expansion during LA development. The paucity of immunogenic B burgdorferi epitopes supports previous findings suggesting CD4+ T-cell responses are suppressed in murine LA. [ABSTRACT FROM AUTHOR]

The family Borreliaceae contains arthropod-borne spirochetes that cause two widespread human diseases, Lyme disease and relapsing fever. Lyme disease is a subacute, progressive illness with variable stage and tissue manifestations. Relapsing fever is an acute febrile illness with prominent bacteremia that may recur and disseminate, particularly to the nervous system. Clinical heterogeneity is a hallmark of both diseases. While human clinical manifestations are influenced by a wide variety of factors, including immune status and host genetic susceptibility, there is evidence that Borreliaceae microbial factors influence the clinical manifestations of human disease caused by this family of spirochetes. Despite these associations, the spirochete genes that influence the severity and manifestations of human disease are, for the most part, unknown. Recent work has identified lineage-specific expansions of lipoproteome-rich accessory genome elements in virulent clones of Borrelia burgdorferi. Using publicly available genome assemblies, it is shown that all Borreliaceae lineages for which sufficient sequence data are available harbor a similar pattern of strongly structured, lineage-specific expansions in their accessory genomes, particularly among lipoproteins, and that this pattern holds across phylogenetic scales including genera, species, and genotypes. The relationships among pangenome elements suggest that infrequent episodes of marked genomic change followed by clonal expansion in geographically and enzootically structured populations may account for the unique lineage structure of Borreliaceae. This analysis informs future genotype–phenotype studies among Borreliaceae and lays a foundation for studies of individual gene function guided by phylogenetic patterns of conservation, diversification, gain, and/or loss. [ABSTRACT FROM AUTHOR]

Background Modified 2-tiered testing (MTTT) for Lyme disease utilizes automatable, high throughput immunoassays (AHTIs) in both tiers without involving western immunoblots, offering performance and practical advantages over standard 2-tiered testing (STTT; first-tier AHTI followed by immunoglobulin M (IgM) and immunoglobulin G (IgG) western immunoblots). For MTTT, Centers for Disease Control and Prevention recommends using AHTI test kits that have been cleared by Food and Drug Administration (FDA) specifically for this intended use. We evaluated performance of FDA-cleared MTTT commercial test kits from 3 manufacturers by comparing with STTT results. Methods We performed MTTT (total antibody AHTI with reflex to separate IgM and IgG AHTIs) using test kits from Diasorin, Gold Standard Diagnostics (GSD), and Zeus Scientific on 382 excess serum samples submitted to the clinical laboratory for routine Lyme disease serologic testing in July 2018, measuring agreement between MTTT and STTT using the κ statistic. Results Overall agreement with STTT was 0.87 (95% confidence interval [CI],.77–.97) using Diasorin assays (almost perfect agreement), 0.80 (95% CI,.68–.93) using GSD assays (substantial agreement) and 0.79 (95% CI,.68–.90) using Zeus assays (substantial agreement). For detection of IgM reactivity, agreement between MTTT and STTT was 0.70 (.51–.90; substantial), 0.63 (95% CI,.44–.82; substantial) and 0.56 (95% CI,.38–.73; moderate), respectively. For detection of IgG reactivity, MTTT/STTT agreement was 0.73 (95% CI,.58–.88), 0.78 (95% CI,.62–.94), and 0.75 (95% CI,.60–.90), respectively (substantial agreement in all cases). Conclusions MTTT results obtained using commercial test kits from 3 different manufacturers had substantial to almost perfect agreement with STTT results overall and moderate to substantial agreement for IgM and IgG detection independently. Commercial MTTT tests can be used broadly for the diagnosis of Lyme disease. [ABSTRACT FROM AUTHOR]

Lyme disease is a zoonotic infection due to Ixodes tick–transmitted Borrelia burgdorferi sensu lato spirochetes and the most common vector-borne disease in the Northern Hemisphere. Despite nearly 50 years of investigation, the pathogenesis of this infection and its 2 main adverse outcomes—postinfectious Lyme arthritis and posttreatment Lyme disease syndrome—are incompletely understood. Advancement in sequencing and mass spectrometry have led to the rapid expansion of high-throughput omics technologies, including transcriptomics, metabolomics, and proteomics, which are now being applied to human diseases. This review summarizes findings of omics studies conducted on blood and tissue samples of people with acute Lyme disease and its postinfectious outcomes. [ABSTRACT FROM AUTHOR]

In the 40 years since Steere and colleagues first described Lyme disease, the illness has increased in incidence and distribution to become the most common vector-borne disease in the United States. Public health officials have developed, implemented, and revised surveillance systems to describe and monitor the condition. Much has been learned about the epidemiology of the illness, despite practical and logistical constraints that have encumbered the collection and interpretation of surveillance data. Future development of automated data collection from electronic health records as a source of surveillance and clinical information will address practical challenges and help answer ongoing questions about complications and persistent symptoms. Robust surveillance will be essential to monitor the effectiveness and safety of future vaccines and other preventive measures. [ABSTRACT FROM AUTHOR]

Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted by Ixodes spp ticks. The rise in Lyme disease cases since its discovery in the 1970s has reinforced the need for a vaccine. A vaccine based on B burgdorferi outer surface protein A (OspA) was approved by the Food and Drug Administration (FDA) several decades ago, but was pulled from the market a few years later, reportedly due to poor sales, despite multiple organizations concluding that it was safe and effective. Newer OspA-based vaccines are being developed and are likely to be available in the coming years. More recently, there has been a push to develop vaccines that target the tick vector instead of the pathogen to inhibit tick feeding and thus prevent transmission of tick-borne pathogens to humans and wildlife reservoirs. This review outlines the history of Lyme disease vaccines and this movement to anti-tick vaccine approaches. [ABSTRACT FROM AUTHOR]

Lyme arthritis (LA) was recognized as a separate entity in 1975 because of geographic clustering of children often diagnosed with juvenile rheumatoid arthritis in Lyme, Connecticut. After identification of erythema migrans as a common early feature of the illness, a prospective study of such patients implicated Ixodes scapularis ticks in disease transmission. In 1982, the causative agent, now called Borrelia burgdorferi , was cultured from these ticks and from Lyme disease patients. Subsequently, it was shown that LA could usually be treated successfully with oral antibiotics but sometimes required intravenous antibiotics. Yet, a small percentage of patients developed a dysregulated, proinflammatory immune response leading to persistent postinfectious synovitis with vascular damage, cytotoxic and autoimmune responses, and fibroblast proliferation, a lesion similar to that of rheumatoid arthritis. The message from postinfectious LA for other autoimmune arthritides is that a complex immune response with autoimmune features can begin with a microbial infection. [ABSTRACT FROM AUTHOR]

Tick vectors and tick‐borne disease are increasingly impacting human populations globally. An important challenge is to understand tick movement patterns, as this information can be used to improve management and predictive modelling of tick population dynamics. Evolutionary analysis of genetic divergence, gene flow and local adaptation provides insight on movement patterns at large spatiotemporal scales. We develop low coverage, whole genome resequencing data for 92 blacklegged ticks, Ixodes scapularis, representing range‐wide variation across the United States. Through analysis of population genomic data, we find that tick populations are structured geographically, with gradual isolation by distance separating three population clusters in the northern United States, southeastern United States and a unique cluster represented by a sample from Tennessee. Populations in the northern United States underwent population contractions during the last glacial period and diverged from southern populations at least 50 thousand years ago. Genome scans of selection provide strong evidence of local adaptation at genes responding to host defences, blood‐feeding and environmental variation. In addition, we explore the potential of low coverage genome sequencing of whole‐tick samples for documenting the diversity of microbial pathogens and recover important tick‐borne pathogens such as Borrelia burgdorferi. The combination of isolation by distance and local adaptation in blacklegged ticks demonstrates that gene flow, including recent expansion, is limited to geographical scales of a few hundred kilometres. [ABSTRACT FROM AUTHOR]

Simple Summary: Dermacentor reticulatus is an arthropod vector with great medical and veterinary importance. Its wide distribution and biological characteristics determine its important role in the circulation of pathogens in the parasite–host system. Its occurrence range is divided into western and eastern populations, which are separated from each other by the so-called Dermacentor-free zone localized in central Poland. This study aimed to estimate the potential epidemiological significance of D. reticulatus in the new endemic focus west of the Vistula River (Upper Silesia, central–southern Poland) and its co-occurrence with Ixodes ricinus. The molecular studies revealed the presence of Rickettsia spp. in 23.8% of the D. reticulatus specimens. In turn, 94.1% of the I. ricinus adults were infected with B. burgdorferi s.l., 11.7% with Babesia spp., and 5.8% with Rickettsia spp. Polymicrobial infections were noted in 17.6% of the I. ricinus. Our finding emphasizes the risk of infestation by both tick species and the risk of tick-borne infections in an area previously thought to be free of Dermacentor ticks. It is necessary to enhance medical and veterinary services for the more efficient diagnosis and prevention of tick-borne diseases in this region. Dermacentor reticulatus (Acari: Ixodidae) is an important arthropod vector in medical and veterinary contexts. Its geographic range is divided into western and eastern populations separated by a "Dermacentor-free zone" in central Poland. Recent faunistic studies showed a new endemic locality of the species in Upper Silesia to the west of the Vistula River (central–southern Poland) and its co-occurrence with I. ricinus. The prevalence of five tick-borne pathogens (TBPs), e.g., B. burgdorferi s.l., Bartonella spp., Rickettsia spp., and Babesia spp., in the ticks was assessed with polymerase chain reaction (PCR) methods. The molecular studies revealed the presence of Rickettsia spp. in 23.8% of the D. reticulatus specimens. In turn, 94.1% of the I. ricinus adults were infected with B. burgdorferi s.l., 11.7 % with Babesia spp., and 5.8% with Rickettsia spp. Coinfections with two TBPs were noted in 17.6% of the I. ricinus. These findings highlight not only the risk of infestation by both tick species in an area previously considered Dermacentor-free, but also the high prevalence of TBPs in the study area. Increased focus on medical and veterinary services appears necessary to diagnose and prevent tick-borne diseases in this region. [ABSTRACT FROM AUTHOR]

Simple Summary: Ticks are spreading at high altitudes in mountain areas and can come into contact with previously unexposed or poorly exposed hosts, such as Alpine ibex (Capra ibex). We collected ticks on ibex and vegetation in the northwestern Italian Alps and tested them for tick-borne pathogens. Ixodes ricinus was the most abundant tick species collected and was infected with Borrelia burgdorferi s.l., Rickettsia spp. and Anaplasma phagocytophilum. Our results suggest that Alpine ibex, like other wild ungulate species, may act as a reservoir for A. phagocytophilum while being an incompetent reservoir for the Lyme borreliosis agent. Future studies should monitor the possible impacts of ticks and transmitted pathogens on the health and conservation of ibex. In the Maritime Alps (northwestern Italy), we collected ticks from vegetation and Alpine ibex (Capra ibex). Ixodes ricinus was the most abundant species in the study area, questing up to 1824 m a.s.l. and infesting 28 out of 72 ibexes. Haemaphysalis punctata, H. sulcata and Dermacentor marginatus were also collected. The abundance of questing ticks significantly decreased with altitude, with beechwoods being the preferred habitat. By PCR, we identified Borrelia burgdorferi s.l. in questing I. ricinus (28.3%; 95%CI: 19.4–38.6) but not in specimens collected from animals. Rickettsia spp. infected both questing (20.6%; 95%CI: 12.9–30.3) and on-host (30.2%; 95%CI: 21.2–40.4) I. ricinus. Anaplasma phagocytophilum was detected in 4.3% (95%CI: 1.2–10.8) of questing I. ricinus and in 45.3% (95%CI: 34.6–56.4) of I. ricinus collected from ibex. Female I. ricinus collected on animals were significantly more infected with A. phagocytophilum than females collected from vegetation (OR = 11.7; 95%CI: 3.8–48.1). By amplifying and sequencing a fragment of the groEL gene, we identified 13 groEL haplotypes, clustering with ecotypes I and II; ecotype I, prevalent in our sample, is considered zoonotic. Our study demonstrates the presence of different tick-borne zoonotic agents in the study area, encompassing a wide altitudinal range, as confirmed by the ticks found on ibex, a typical mountain-dwelling mammal. The results also confirm the altitudinal range expansion of ticks and associated pathogens in the Alps and suggest that Alpine ibex may act as a reservoir for A. phagocytophilum, as do other wild ungulate species. [ABSTRACT FROM AUTHOR]