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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]

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]

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]

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]

Background and Purpose: We need more knowledge on clinical presentations, time course, biomarkers, and prognosis in European Lyme neuroborreliosis (LNB). Methods: A prospective 12‐month follow‐up of predetermined clinical and laboratory parameters was undertaken in 105 patients with LNB. Results: At presentation, 79% had radiculopathy, 49% had facial palsy, and 13% had solely subjective symptoms (predominately pain). Intrathecally produced Borrelia burgdorferi (Bb) antibodies were demonstrated and cerebrospinal fluid (CSF) CXCL13 was positive in 85% and 82% pretreatment, in 73% and 10% at 6 months, and in 58% and 14% at 12 months, respectively. CSF Bb polymerase chain reaction (PCR) was positive in 40% pretreatment. In four patients who tested negative for Bb antibodies in both serum and CSF, the diagnosis was supported by typical clinical features, pleocytosis, CSF Bb‐PCR (n = 1), or CSF CXCL13 (n = 2). The proportion with symptoms influencing daily life was 91% pretreatment, 25% at 10 weeks, 20% at 6 months, and 15% at 12 months. Fatigue was the most common complaint at 12 months. A high burden of symptoms before and after treatment was associated with residual complaints at 12 months, whereas background data, other clinical features, and laboratory features were not. Conclusions: LNB can present with solely subjective symptoms, especially pain. Many LNB patients have persistent Bb antibodies in serum and CSF. In seronegative LNB, CSF Bb‐PCR and CXCL13 may give diagnostic support. CXCL13 may be persistently positive after treatment in some patients. Most of the clinical improvement occurs during the first 10 weeks. High initial clinical score is associated with poorer outcome. [ABSTRACT FROM AUTHOR]

Background: Lyme disease (LD), the most common vector‐borne disease in the United States, typically presents with a localised erythema migrans rash (EM). Left untreated, infection can disseminate to cause severe heart, joint or nervous system manifestations. Summaries of LD surveillance data have been published previously but did not include the frequency, demographic or clinical characteristics of LD cases during pregnancy. Methods: We summarised confirmed and probable LD cases by pregnancy status as reported to the U.S. Centers for Disease Control and Prevention during 1992–2019. We defined an LD case during pregnancy as one with (1) female sex, (2) age 14–49 years and (3) positive pregnancy indication. We evaluated the frequency, seasonality, age distribution, race and ethnicity, geographic distribution and clinical manifestations of LD cases during pregnancy and cases among non‐pregnant females. We compared proportions using chi‐squared tests. Results: Among 698,876 reported LD cases, 112,002 (16%) were confirmed or probable cases among females aged 14–49 years; 32,301 (29%) were specifically reported as non‐pregnant and 643 (0.6%) (568 confirmed and 75 probable cases) reported as pregnant. Illness onset peaked in June among LD cases during pregnancy, but in July for cases among non‐pregnant females. A higher proportion of confirmed LD cases during pregnancy had only EM rash than did cases among non‐pregnant females (66% vs. 60%, p = 0.019). Conclusions: LD cases during pregnancy are rare. Compared to non‐pregnant females, cases among pregnant females more commonly involve early clinical manifestations. These patterns could suggest earlier detection or more complete reporting of LD cases during pregnancy than their non‐pregnant counterparts. Earlier detection could be due to frequent contact with healthcare or increased self‐advocacy during pregnancy. Prompt antimicrobial treatment is critical for preventing severe disease and reducing risk of adverse pregnancy or birth outcomes. [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]

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]

Emerging and re‐emerging pathogens often stem from zoonotic origins, cycling between humans and animals, and are frequently vectored and maintained by hematophagous arthropod vectors. The efficiency by which these disease agents are successfully transmitted between vertebrate hosts is influenced by many factors, including the host on which a vector feeds. The Lyme disease bacterium Borrelia burgdorferi sensu lato has adapted to survive in complex host environments, vectored by Ixodes ticks, and maintained in multiple vertebrate hosts. The versatility of Lyme borreliae in disparate host milieus is a compelling platform to investigate mechanisms dictating pathogen transmission through complex networks of vertebrates and ticks. Squamata, one of the most diverse clade of extant reptiles, is comprised primarily of lizards, many of which are readily fed upon by Ixodes ticks. Yet, lizards are one of the least studied taxa at risk of contributing to the transmission and life cycle maintenance of Lyme borreliae. In this review, we summarize the current evidence, spanning from field surveillance to laboratory infection studies, supporting their contributions to Lyme borreliae circulation. We also summarize the current understanding of divergent lizard immune responses that may explain the underlying molecular mechanisms to confer Lyme spirochete survival in vertebrate hosts. This review offers a critical perspective on potential enzootic cycles existing between lizard‐tick‐Borrelia interactions and highlights the importance of an eco‐immunology lens for zoonotic pathogen transmission studies. [ABSTRACT FROM AUTHOR]

Background: The evidence on the prevalence of Lyme borreliosis (LB) is limited, but there is a suspicion of overdiagnosis of LB in recent years. We reviewed the LB diagnosis and treatment‐related data in Türkiye, based on the Infectious Diseases Society of America (IDSA) 2020 and European Society of Clinical Microbiology and Infectious Diseases Study Group for Lyme Borreliosis (ESGBOR) 2018 guidelines. By detecting the disagreements between these two, we outlined the areas to be improved for future guidelines. Methods: We performed a literature search according to the PRISMA guidelines in PubMed, Ovid‐Medline, Web of Science, Turkish Medline, Scopus, CINAHL, ULAKBIM TR Index, Google Scholar and Cochrane Library databases. We included the published cases in a database and evaluated according to IDSA and ESGBOR guidelines. We outlined the reasons for misdiagnoses and inappropriate uses of antibiotics. Results: We included 42 relevant studies with 84 LB cases reported from Türkiye between 1990 and December 2022. Among 84 cases, the most common clinical findings were nervous system findings (n = 37, 44.0%), erythema migrans (n = 29, 34.5%) and ophthalmologic findings (n = 15, 17.9%). The IDSA 2020 and ESGBOR 2018 guidelines agreed on the diagnosis of 71 (84.5%) cases; there was an agreement that 31 cases (36.9%) were misdiagnosed and 40 cases (47.6%) were correctly diagnosed, and there was disagreement for 13 cases (15.5%). Serum immunoglobulin M (IgM), IgG measurements by ELISA and western blot were widely performed, and they were effective in definitive diagnosis merely when used according to guidelines. Inappropriate use of antibiotics was detected in 42 (50.0%) of cases which were classified in the following categories: incorrect LB diagnosis, inappropriate choice of antibiotic, inappropriate route of drug administration and prolonged antibiotic treatment. Conclusion: Overdiagnosis and non‐adherence to guidelines is a common problem. The discordance between seroprevalence and clinical studies necessitates a consensus over the best clinical approach. [ABSTRACT FROM AUTHOR]

Aims: Urban green spaces are locations of maximal human activity, forming areas of enhanced risk for tick‐borne disease (TBD) transmission. Being also limited in spatial scale, green spaces form prime targets for control schemes aiming to reduce TBD risk. However, for effective control, the key species maintaining local tick and tick‐borne pathogen (TBP) populations must be identified. To determine how patterns of host utilization vary spatially, we utilized blood meal analysis to study the contributions of voles, shrews, squirrels, leporids and cervids towards blood meals and the acquisition of TBPs of juvenile Ixodes ricinus in urban and sylvatic areas in Finland. Methods and Results: A total of 1084 nymphs were collected from the capital city of Finland, Helsinki and from a sylvatic island in southwestern Finland, and subjected to qPCR analysis to identify DNA remnants of the previous host. We found significant differences in host contributions between urban and sylvatic environments. Specifically, squirrels and leporids were more common hosts in urban habitats, whereas cervids and voles were more common in sylvatic habitats. In addition to providing 18.4% of larval blood meals in urban habitats, red squirrels were identified as the source of 28.6% (n = 48) of Borrelia afzelii detections and 58.1% (n = 18) of Borrelia burgdorferi sensu stricto detections, indicating an important role for local enzootic cycles. Conclusions: Our study highlights that the key hosts maintaining tick and TBP populations may be different in urban and sylvatic habitats. Likewise, hosts generally perceived as important for upkeep may have limited importance in urban environments. Consequently, targeting control schemes based on off‐site data of host importance may lead to suboptimal results. [ABSTRACT FROM AUTHOR]

Lyme borreliosis (LB) is the most common vector‐borne disease in the Northern Hemisphere caused by spirochetes belonging to the Borrelia burgdorferi sensu lato (Bbsl) complex. Borrelia spirochetes circulate in obligatory transmission cycles between tick vectors and different vertebrate hosts. To successfully complete this complex transmission cycle, Bbsl encodes for an arsenal of proteins including the PFam54 protein family with known, or proposed, influences to reservoir host and/or vector adaptation. Even so, only fragmentary information is available regarding the naturally occurring level of variation in the PFam54 gene array especially in relation to Eurasian‐distributed species. Utilizing whole genome data from isolates (n = 141) originated from three major LB‐causing Borrelia species across Eurasia (B. afzelii, B. bavariensis, and B. garinii), we aimed to characterize the diversity of the PFam54 gene array in these isolates to facilitate understanding the evolution of PFam54 paralogs on an intra‐ and interspecies level. We found an extraordinarily high level of variation in the PFam54 gene array with 39 PFam54 paralogs belonging to 23 orthologous groups including five novel paralogs. Even so, the gene array appears to have remained fairly stable over the evolutionary history of the studied Borrelia species. Interestingly, genes outside Clade IV, which contains genes encoding for proteins associated with Borrelia pathogenesis, more frequently displayed signatures of diversifying selection between clades that differ in hypothesized vector or host species. This could suggest that non‐Clade IV paralogs play a more important role in host and/or vector adaptation than previously expected, which would require future lab‐based studies to validate. [ABSTRACT FROM AUTHOR]

Background: Anaplasma phagocytophilum is a tick‐borne bacterium and the cause of human granulocytic anaplasmosis (HGA). Here, we report a case of transfusion‐transmitted (TT)‐HGA involving a leukoreduced (LR) red blood cell (RBC) unit. Case Report: A 64‐year‐old woman with gastric adenocarcinoma and multiple myeloma who received weekly blood transfusions developed persistent fevers, hypotension, and shortness of breath 1 week after receiving an RBC transfusion. Persistent fevers, new thrombocytopenia, and transaminitis suggested a tick‐borne infection. Results: The absence of blood parasites on thick and thin blood smears suggested that malaria and Babesia infection were not present, and the recipient tested negative for antibodies to Borrelia burgdorferi. Blood testing by polymerase chain reaction (PCR) for Ehrlichia and Anaplasma species identified A. phagocytophilum. Treatment with doxycycline resolved the infection; however, the recipient expired due to complications of her known malignancies. The recipient lived in a nursing home and did not have pets or spend time outdoors. The donor was a female in her 70s from Maine who was diagnosed with HGA 3 weeks after donating blood and whose LR‐RBCs from the donation were transfused to the recipient 9 days following collection. Conclusion: This is a confirmed case of TT‐HGA. Although rare, TT‐HGA has been reported with LR‐RBCs and platelets. In endemic areas, testing for tick‐borne associated infections should be considered when investigating post‐transfusion complications. [ABSTRACT FROM AUTHOR]

Lyme borreliosis, caused by Borrelia burgdorferi sensu lato, is the most common tickborne disease. Its neuronal form, neuroborreliosis, comprises 3 to 38% of borreliosis cases in Europe. Borrelia outer surface proteins and virulence factors, OspE and BBK32, have been previously reported to help cause infection by promoting attachment to human host epithelial cells and evading complement attack. We assessed the serological responses to BBK32 and OspE in 19 individuals diagnosed with neuroborreliosis to see whether antibodies that could both target the bacteria and neutralize the virulence mechanisms on the microbial surface emerge. Results evaluate levels of total protein, IgG and the chemokine CXCL13, a determinant for B‐cell recruitment during neuroinflammation, in patients' cerebrospinal fluid samples. Antibody levels against BBK32 and OspE correlated with those against VlsE, a well‐characterized diagnostic serological marker of the disease. A dual serological profile of the patients was observed. K‐means clustering split the cohort into two discrete groups presenting distinct serological and CNS responses. One group contained young patients with low levels of anti‐BBK32 and OspE antibodies. The other group showed stronger responses, possibly following prolonged infections or reinfections. Additionally, we assessed anti‐ganglioside antibodies that could cause autoimmunity or complement dysregulation but observed that they did not correlate with neuroborreliosis in our patient cohort. The dual nature of antibody responses against the virulence factors BBK32 and OspE in neuroborreliosis patients may suggest the necessity of repeated exposures for efficient immune responses. Better protection could be achieved if the virulence factors were formulated into vaccines. [ABSTRACT FROM AUTHOR]

Background: Starting in the early 20th century, ticks and their pathogens have been detected during surveillance efforts in Canada. Since then, the geographic spread of tick vectors and tick‐borne pathogens has steadily increased in Canada with the establishment of tick and host populations. Sentinel surveillance in Canada primarily focuses on Ixodes scapularis, which is the main vector of Borrelia burgdorferi, the bacterium causing Lyme disease. Other tick‐borne pathogens, such as Anaplasma, Babesia, and Rickettsia species, have lower prevalence in Canada, but they are emerging or re‐emerging in tick and host populations. Aims/Materials & Methods: Here, we assessed the historical associations between tick vectors, hosts and pathogens and identified spatiotemporal clusters of pathogen presence in ticks in Canada using data extracted from the literature. Results: Approximately one‐third of ticks were infected with a pathogen, and these ticks were feeding primarily on bird and mammal hosts. B. burgdorferi was the most detected pathogen and I. scapularis harboured the greatest number of pathogens. We identified several spatial outliers of high pathogen presence in ticks in addition to five spatiotemporal clusters in southern Canada, all of which have long‐established tick populations. Six spatiotemporal clusters of high pathogen presence in ticks were also identified based on surveillance method, with four clusters associated with passive surveillance and two clusters associated with active surveillance. Discussion: Our review represents the first systematic assessment of the literature that identifies historical associations and spatiotemporal changes in tick‐host‐pathogen disease systems in Canada over broad spatial and temporal scales. Conclusion: As distinct spatiotemporal clusters were identified based on surveillance method, it is imperative that surveillance efforts employ standardized methods and data reporting to comprehensively assess the presence, spread and risk of tick‐borne pathogens in tick and host populations. [ABSTRACT FROM AUTHOR]

The tick, Ixodes scapularis, vectors pathogens such as Borrelia burgdorferi, the bacterium that causes Lyme disease. Over the last few decades I. scapularis has expanded its range, introducing a novel health threat into these areas. Warming temperatures appear to be one cause of its range expansion to the north. However, other factors are also involved. We show that unfed adult female ticks infected with B. burgdorferi have greater overwintering survival than uninfected female ticks. Locally collected adult female ticks were placed in individual microcosms and allowed to overwinter in both forest and dune grass environments. In the spring we collected the ticks and tested both dead and living ticks for B. burgdorferi DNA. Infected ticks had greater overwintering survival compared with uninfected ticks every winter for three consecutive winters in both forest and dune grass environments. We discuss the most plausible explanations for this result. The increased winter survival of adult female ticks could enhance tick population growth. Our results suggest that, in addition to climate change, B. burgdorferi infection itself may be promoting the northern range expansion of I. scapularis. Our study highlights how pathogens could work synergistically with climate change to promote host range expansion. [ABSTRACT FROM AUTHOR]

Untangling how factors such as environment, host, associations among bacterial species and dispersal predict microbial composition is a fundamental challenge. In this study, we use complementary machine‐learning approaches to quantify the relative role of these factors in shaping microbiome variation of the blacklegged tick Ixodes scapularis. I. scapularis is the most important vector for Borrelia burgdorferi (the causative agent for Lyme disease) in the U.S. as well as a range of other important zoonotic pathogens. Yet the relative role of the interactions between pathogens and symbionts compared to other ecological forces is unknown. We found that positive associations between microbes where the occurrence of one microbe increases the probability of observing another, including between both pathogens and symbionts, was by far the most important factor shaping the tick microbiome. Microclimate and host factors played an important role for a subset of the tick microbiome including Borrelia (Borreliella) and Ralstonia, but for the majority of microbes, environmental and host variables were poor predictors at a regional scale. This study provides new hypotheses on how pathogens and symbionts might interact within tick species, as well as valuable predictions for how some taxa may respond to changing climate. [ABSTRACT FROM AUTHOR]

Deer keds, such as Lipoptena cervi Linnaeus (Diptera: Hippoboscidae), are blood‐feeding flies from which several human and animal pathogens have been detected, including Borrelia burgdorferi sensu lato Johnson (Spirochaetales: Borreliaceae), the causative agent of Lyme disease. Cervids (Artiodactyla: Cervidae), which are the primary hosts of deer keds, are not natural reservoirs of B. burgdorferi sl, and it has been suggested that deer keds may acquire bacterial pathogens via co‐feeding near infected ticks. We screened L. cervi (n = 306) and Ixodes scapularis Say (Ixodida: Ixodidae) (n = 315) collected from 38 white‐tailed deer in Pennsylvania for the family Anaplasmataceae, Bartonella spp. (Hyphomicrobiales: Bartonellaceae), Borrelia spp., and Rickettsia spp. (Rickettsiales: Rickettsiaceae). Limited similarity in the bacterial DNA detected between these ectoparasites per host suggested that co‐feeding may not be a mechanism by which deer keds acquire these bacteria. The feeding biology and life history of deer keds may impact the observed results, as could the season when specimens were collected. We separately screened L. cervi (n = 410), L. mazamae Róndani (n = 13), L. depressa Say (n = 10), and Neolipoptena ferrisi Bequaert (n = 14) collections from locations within the United States and Canada for the same pathogens. These results highlight the need to further study deer ked‐host and deer ked‐tick relationships. [ABSTRACT FROM AUTHOR]

Understanding which factors determine tick‐borne disease hazard can contribute to effective disease control. In Europe, the hazard of the pathogens Borrelia burgdorferi s.l. and Anaplasma phagocytophilum is determined by local tick densities (mainly Ixodes ricinus) and the reservoir competence of the host species community. Sand lizards (Lacerta agilis) are common hosts for larvae and nymphs of I. ricinus and non‐competent reservoirs for both pathogens. Consequently, high relative abundance of L. agilis is hypothesized to be associated with lower infection prevalence in nymphs. Here, we aimed to test whether this effectively occurs in natural settings.We sampled different habitat types within a heterogenous dune landscape at the Dutch coast and estimated (1) L. agilis densities, (2) host community competence, (3) the density and infection prevalence of questing I. ricinus ticks and (4) the number and infection prevalence of ticks feeding on L. agilis.Captured L. agilis had high tick burdens and contributed substantially to feeding I. ricinus larvae in their natural habitat. B. burgdorferi s.l. and A. phagocytophilum were virtually absent from feeding larvae and nymphs.The nymphal infection prevalence of both pathogens in questing ticks was lower in habitat types where L. agilis was more abundant. Hence, L. agilis strongly reduced community competence.The density of questing nymphs was higher in habitat types with denser vegetation and also varied more between habitat types than infection prevalence. As a result, nymphal density had a stronger effect on the density of infected ticks than did nymphal infection prevalence.Synthesis and applications. Coastal dune habitats favourable for L. agilis have lower densities of questing nymphs and a lower human infection hazard. These results might be applicable to similar ecosystems where L. agilis is present. From a public health perspective, this underlines the importance of preserving early successional habitat, as encroaching shrubs are associated with higher tick‐borne disease hazard, and vegetation removal might be a solution to reduce hazard in coastal dunes. The high degree of spatial heterogeneity in the abundance of tick‐borne pathogens also poses opportunities to manage recreational activities to limit human exposure to tick‐borne diseases. [ABSTRACT FROM AUTHOR]

Borrelia spirochetes are unique among diderm bacteria in their lack of lipopolysaccharide (LPS) in the outer membrane (OM) and their abundance of surface‐exposed lipoproteins with major roles in transmission, virulence, and pathogenesis. Despite their importance, little is known about how surface lipoproteins are translocated through the periplasm and the OM. Here, we characterized Borrelia burgdorferi BB0838, a distant homolog of the OM LPS assembly protein LptD. Using a CRISPR interference approach, we showed that BB0838 is required for cell growth and envelope stability. Upon BB0838 knockdown, surface lipoprotein OspA was retained in the inner leaflet of the OM, as determined by its inaccessibility to in situ proteolysis but its presence in OM vesicles. The topology of the OM porin/adhesin P66 remained unaffected. Quantitative mass spectrometry of the B. burgdorferi membrane‐associated proteome confirmed the selective periplasmic retention of surface lipoproteins under BB0838 knockdown conditions. Additional analysis identified a single in situ protease‐accessible BB0838 peptide that mapped to a predicted β‐barrel surface loop. Alphafold Multimer modeled a B. burgdorferi LptB2FGCAD complex spanning the periplasm. Together, this suggests that BB0838/LptDBb facilitates the essential terminal step in spirochetal surface lipoprotein secretion, using an orthologous OM component of a pathway that secretes LPS in proteobacteria. [ABSTRACT FROM AUTHOR]

PlzA is a c‐di‐GMP‐binding protein crucial for adaptation of the Lyme disease spirochete Borrelia (Borreliella) burgdorferi during its enzootic life cycle. Unliganded apo‐PlzA is important for vertebrate infection, while liganded holo‐PlzA is important for survival in the tick; however, the biological function of PlzA has remained enigmatic. Here, we report that PlzA has RNA chaperone activity that is inhibited by c‐di‐GMP binding. Holo‐ and apo‐PlzA bind RNA and accelerate RNA annealing, while only apo‐PlzA can strand displace and unwind double‐stranded RNA. Guided by the crystal structure of PlzA, we identified several key aromatic amino acids protruding from the N‐ and C‐terminal domains that are required for RNA‐binding and unwinding activity. Our findings illuminate c‐di‐GMP as a switch controlling the RNA chaperone activity of PlzA, and we propose that complex RNA‐mediated modulatory mechanisms allow PlzA to regulate gene expression during both the vector and host phases of the B. burgdorferi life cycle. [ABSTRACT FROM AUTHOR]

Ticks are found across a range of habitats, with woodland being particularly important for high densities and prevalence of Borrelia infection. Assessments of risk in urban woodland can be difficult if there are low densities and small sample sizes for Borrelia prevalence estimates. This study targeted six urban woodlands with established tick populations, as well as six woodlands in peri‐urban zones and six woodlands in rural zones in and around the cities of Bath and Southampton, in the South of England. Nymph densities were estimated, and 100 nymphs were tested from each of the 18 woodlands studied. Ixodes ricinus ticks were found in all woodlands surveyed, and overall density of nymphs (DON) per 100 m2 was 18.17 in urban woodlands, 26.0 in peri‐urban woodlands and 17.67 in rural woodlands. Out of 600 nymphs tested across urban woodlands, 10.3% were infected with Borrelia. The same proportion of nymphs collected in rural woodlands were positive for Borrelia. In peri‐urban woodlands, 10.8% of nymphs tested positive. Across both cities combined, density of infected nymphs (DIN) was 2.73 per 100 m2 in peri‐urban woodland, 1.87 per 100 m2 in urban woodland and 1.82 per 100 m2 in rural woodland. Overall, DON, Borrelia prevalence and DIN did not differ significantly along an urban–rural gradient. This suggests the risk of Lyme borreliosis transmission could be similar, or perhaps even elevated in urban woodland if there is higher public footfall, subsequent contact with ticks and less awareness of the risks. This is particularly important from a public health perspective, as Borrelia garinii dominated across the gradient and this genospecies is linked to neuroborreliosis. [ABSTRACT FROM AUTHOR]

In August 2021, the Nebraska Department of Health and Human Services was notified by a local public health department of a cluster of two Lyme disease cases in patients with local exposure to wooded areas in a county located in their jurisdiction. Epidemiological investigations revealed that the two patients had similar symptom onset dates and had likely exposure to ticks at wooded sites located directly adjacent to one another. Two environmental investigations were completed in October 2021 and consisted of tick surveys at the patients' reported sites of tick exposure. 12 ticks were collected across the two surveys and identified the black‐legged tick (Ixodes scapularis). During subsequent testing of the collected ticks, spirochete bacteria were isolated, cultured and confirmed as Borrelia burgdorferi sensu stricto by PCR. In total, 7 of 12 (58.3%) I. scapularis ticks tested positive for B. burgdorferi s.s. The results of this study document the fourth known established population of I. scapularis in Nebraska and confirms the first detection of B. burgdorferi s.s. in field collected ticks from Nebraska. The epidemiological and environmental investigation data provide the first evidence for local Lyme disease transmission occurring within Nebraska. These findings highlight the need for continued surveillance of I. scapularis and its associated pathogens in Nebraska to further characterize human risk and monitor emergence into other areas of the state. [ABSTRACT FROM AUTHOR]

Lyme disease risk areas have increased across Canada in recent decades with the ongoing range expansion of Ixodes scapularis and Borrelia burgdorferi. Different methodologies are used by federal and provincial governments to determine local Lyme disease risk, which can make comparisons between regions challenging. In this study, seven Canadian Lyme disease risk classification methodologies were compared with each other to highlight the strengths and limitations of how each definition measured I. scapularis and B. burgdorferi risk. Each methodology was applied to active surveillance data from Ontario, and per cent agreement and kappa statistics were calculated. The methodologies varied in their measurements of the risk of exposure to I. scapularis and B. burgdorferi based on their use of active surveillance techniques, multiple types of collected surveillance data and laboratory confirmation of B. burgdorferi. Most initial Lyme disease risk site classifications were maintained over time. Kappa and per cent agreement statistics highlighted large differences between 8 of the 15 methodology pairings, indicating the presence of inconsistencies between most methodologies. Accurate, consistent surveillance and assessment of the spread of I. scapularis and its pathogens will aid with communicating Lyme disease risk to the public and preventing tick‐borne pathogen transmission. [ABSTRACT FROM AUTHOR]

Background and purpose: Currently there is an unmet need for a highly standardized blood biomarker test to monitor treatment response in Lyme neuroborreliosis (LNB). Differentiating between active or past infection is challenged by the relatively high frequency of persistent symptoms after the end of antibiotic treatment (estimated 15%–20%), the variable clinical course and the long‐lasting Borrelia burgdorferi antibodies. The aim was therefore to evaluate plasma neurofilament light chain (pNfL) as a marker for disease activity in LNB. Methods: This was a prospective cohort of definite LNB (N = 36) with blood samples and clinical evaluation including Glasgow Outcome Score at treatment initiation and 3 and 6 months' follow‐up. Consecutive plasma was retrospectively analysed for the content of neurofilament light chain by Quanterix® kits (Simoa® NF‐light Kit). Results: Plasma neurofilament light chain significantly decreased between treatment initiation and the 3‐month follow‐up (median 83 pg/ml vs. median 14 pg/ml (25 pairs), p < 0.0001). No significant change was observed between 3 and 6 months' follow‐up (median 14 pg/ml vs. median 12 pg/ml (21 pairs), p = 0.33). At treatment initiation 90% had pNfL above the age‐defined reference compared to only 23% and 7% respectively at 3 and 6 months' follow‐up. Decreases in pNfL were mirrored by increasing Glasgow Outcome Score. Reporting persistent symptoms at the 6‐month follow‐up was not associated with pNfL (relative change from reference or actual values) at baseline or at 6 months' follow‐up. Conclusion: Plasma neurofilament light chain decreases following antibiotic treatment in LNB and is not associated with reporting persistent symptoms. It was therefore speculated that it may prove useful as a treatment response biomarker in LNB. [ABSTRACT FROM AUTHOR]

The effects of systemic pathogens on gut microbiota of wild animals are poorly understood. Furthermore, coinfections are the norm in nature, yet most studies of pathogen–microbiota interactions focus on effects of single pathogen infections on gut microbiota.We examined the effects of four systemic pathogens (bacteria Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato, apicomplexan protozoa Babesia microti and Puumala orthohantavirus) and coinfections among them on the (bacterial) gut microbiota of wild bank voles Myodes glareolus.We hypothesized that: (1) the effects of coinfection on gut microbiota generally differ from those of a single pathogen infection, (2) systemic pathogens have individual (i.e. distinct) associations with gut microbiota, which are modified by coinfection and (3) the effects of coinfection (compared with those of single infection) are idiosyncratic (i.e. pathogen‐specific).The gut microbiota of coinfected bank voles differed from that of single pathogen infected individuals, although, as predicted, the effects of coinfections were unique for each pathogen. After accounting for coinfections, only Puumala orthohantavirus was associated with higher α‐diversity; however, all pathogens affected gut microbiota ß‐diversity in a pathogen‐specific way, affecting both rare and abundant gut bacteria.Our results showed that the effects of systemic pathogens on host's gut microbiota vary depending on the pathogen species, resulting in idiosyncratic signatures of coinfection. Furthermore, our results emphasize that neglecting the impact of coinfections can mask patterns of pathogen–microbiota associations. [ABSTRACT FROM AUTHOR]

Background and purpose: To diagnose Lyme neuroborreliosis (LNB), cerebrospinal fluid (CSF) is tested for pleocytosis and intrathecal antibody production. The Dutch guideline for Lyme borreliosis indicates a lumbar puncture in the case of positive Borrelia serology or a strong clinical suspicion of LNB. This suggests that LNB might be underdiagnosed in patients with negative Borrelia serology and/or a minor clinical suspicion. The objective was to assess how often negative Borrelia serology occurs in the case of LNB. Method: A retrospective study was performed among patients with LNB visiting Gelre Hospitals between January 2007 and December 2020. Electronic medical records of patients with pleocytosis were reviewed to identify patients with LNB. Data were collected from medical records. Results: Included were 127 patients with LNB, 58 of whom were children. In 67 patients Borrelia antibodies were present in both serum and CSF. In 53 of 67 patients there was intrathecal antibody production. In 28 patients there was intrathecal antibody production but serum antibodies were absent. Of patients with positive serology 77% had antibodies in CSF versus 83% of patients with negative serology (p = 0.435). Of patients with positive serology 61% had intrathecal antibody production versus 78% of patients with negative serology (p = 0.073). Conclusions: Twenty‐eight LNB patients had intrathecal antibody production but no antibodies in serum. In this specific patient population, positive serum serology was not associated with antibodies in CSF nor with intrathecal antibody production. In Lyme endemic areas, in patients with symptoms suggestive for LNB, there is a need to lower the threshold for a lumbar puncture. [ABSTRACT FROM AUTHOR]

Vector‐borne pathogens exist in obligate transmission cycles between vector and reservoir host species. Host and vector shifts can lead to geographic expansion of infectious agents and the emergence of new diseases in susceptible individuals. Three bacterial genospecies (Borrelia afzelii, Borrelia bavariensis, and Borrelia garinii) predominantly utilize two distinct tick species as vectors in Asia (Ixodes persulcatus) and Europe (Ixodes ricinus). Through these vectors, the bacteria can infect various vertebrate groups (e.g., rodents, birds) including humans where they cause Lyme borreliosis, the most common vector‐borne disease in the Northern hemisphere. Yet, how and in which order the three Borrelia genospecies colonized each continent remains unclear including the evolutionary consequences of this geographic expansion. Here, by reconstructing the evolutionary history of 142 Eurasian isolates, we found evidence that the ancestors of each of the three genospecies probably have an Asian origin. Even so, each genospecies studied displayed a unique substructuring and evolutionary response to the colonization of Europe. The pattern of allele sharing between continents is consistent with the dispersal rate of the respective vertebrate hosts, supporting the concept that adaptation of Borrelia genospecies to the host is important for pathogen dispersal. Our results highlight that Eurasian Lyme borreliosis agents are all capable of geographic expansion with host association influencing their dispersal; further displaying the importance of host and vector association to the geographic expansion of vector‐borne pathogens and potentially conditioning their capacity as emergent pathogens. [ABSTRACT FROM AUTHOR]

Background: Ticks are obligate hematophagous arthropods capable of transmitting a great variety of endemic and emerging pathogens causing diseases in animals and humans. Objectives: The aim of this study was to investigate the presence of Bartonella spp., Rickettsia spp., Borrelia burgdorferi sensu lato (s.l.) and Anaplasma phagocytophilum in ticks collected from cattle in Benin and Togo. Methods: Overall, 396 (148 males, 205 females and 43 nymphs) ticks were collected from cattle in 17 districts (Benin and Togo) between 2019 and 2020. Ticks were pooled into groups of 2–6 ticks per pool according to individual host, location, species and developmental stage. The DNA of each pool was extracted for molecular screening. Results: PCR results revealed that 20 tick pools were positive for Bartonella spp. (Benin and Togo) and 23 tick pools positive for Rickettsia spp. (Benin), while all pools were negative for A. phagocytophilum and B. burgdorferi s.l. Sequence analysis of positive Rickettsia samples revealed the presence of Rickettsia aeschlimannii. Conclusions: The present study highlights the presence of zoonotic agents in ticks collected from cattle in Benin and Togo. This information will raise awareness of tick‐borne diseases among physicians and veterinarians, stimulate further studies to monitor these pathogens, and advise on necessary measures to control the spread of these zoonoses. [ABSTRACT FROM AUTHOR]

Lyme disease is a tick‐borne disease prevalent in North America, Europe, and Asia. Despite the accumulated knowledge from epidemiological, in vitro, and in animal studies, the understanding of dissemination of vector‐borne pathogens, such as Borrelia burgdorferi (Bb), remains incomplete with several important knowledge gaps, especially related to invasion and intravasation into circulation. To elucidate the mechanistic details of these processes a tissue‐engineered human dermal microvessel model is developed. Fluorescently labeled Bb are injected into the extracellular matrix (ECM) to mimic tick inoculation. High resolution, confocal imaging is performed to visualize the sub‐acute phase of infection. From analysis of migration paths no evidence to support adhesin‐mediated interactions between Bb and ECM components is found, suggesting that collagen fibers serve as inert obstacles to migration. Intravasation occurs at cell–cell junctions and is relatively fast, consistent with Bb swimming in ECM. In addition, it is found that Bb alone can induce endothelium activation, resulting in increased immune cell adhesion but no changes in global or local permeability. Together these results provide new insight into the minimum requirements for Bb dissemination and highlight how tissue‐engineered models are complementary to animal models in visualizing dynamic processes associated with vector‐borne pathogens. [ABSTRACT FROM AUTHOR]

Increasing temperatures due to climate change have contributed to a northward range expansion of Ixodes scapularis ticks in Canada. These ticks harbour pathogens of public and animal health significance, including Borrelia burgdorferi and Anaplasma phagocytophilum, which cause Lyme disease and anaplasmosis, respectively, in humans, dogs and horses, and Borrelia miyamotoi, which causes a flu‐like relapsing fever in humans. To address the risks associated with these vector‐borne zoonotic diseases, continuous tick surveillance is advised. This study examined spatial patterns of B. burgdorferi, B. miyamotoi and A. phagocytophilum from ticks submitted through a national study on ticks of companion animals. From 1 April 2019 to 31 March 2020, we received a total of 1541 eligible submissions from 94 veterinary clinics across Canada. Individual and pooled samples of a maximum of either 5 I. scapularis, I. pacificus or I. angustus samples from the same animal and of the same life stage were screened using real‐time PCR targeting genes 23S rRNA for Borrelia spp. and msp2 for A. phagocytophilum. Confirmatory testing was conducted on all 23S rRNA positive samples using a duplex assay for ospA and flaB to differentiate B. burgdorferi and B. miyamotoi, respectively. Prevalence estimates were highest (>20%) for B. burgdorferi in southwestern Manitoba, eastern Ontario, southwestern Quebec, New Brunswick and Nova Scotia. Estimates of B. miyamotoi and A. phagocytophilum were much lower (<5%), except for higher A. phagocytophilum (>5%) estimates for southern Manitoba, eastern Ontario and Prince Edward Island. Findings from this study, combined with other surveillance approaches, can be used to guide veterinary and public health approaches for ticks and tick‐borne diseases. [ABSTRACT FROM AUTHOR]

Intracellular compartmentalization of ligands, receptors and signaling molecules has been recognized as an important regulator of inflammation. The toll‐like receptor (TLR) 2 pathway utilizes the trafficking molecule adaptor protein 3 (AP‐3) to activate interleukin (IL)‐6 signaling from within phagosomal compartments. To better understand the vesicular pathways that may contribute to intracellular signaling and cooperate with AP‐3, we performed a vesicular siRNA screen. We identified Rab8 and Rab11 GTPases as important in IL‐6 induction upon stimulation with the TLR2 ligand Pam3CSK4 or the pathogen, Borrelia burgdorferi (Bb), the causative agent of Lyme disease. These Rabs were recruited to late and lysosomal stage phagosomes and co‐transported with TLR2 signaling adaptors and effectors, such as MyD88, TRAM and TAK1, in an AP‐3‐dependent manner. Our data support a model where AP‐3 mediates the recruitment of recycling and secretory vesicles and the assembly of signaling complexes at the phagosome. [ABSTRACT FROM AUTHOR]

Experimental infections with different pathogen strains give insight into pathogen life history traits. The purpose of the present study was to compare variation in tissue infection prevalence and spirochete abundance among strains of Borrelia burgdorferi in a rodent host (Mus musculus, C3H/HeJ). Male and female mice were experimentally infected via tick bite with one of 12 strains. Ear tissue biopsies were taken at days 29, 59 and 89 postinfection, and seven tissues were collected at necropsy. The presence and abundance of spirochetes in the mouse tissues were measured by quantitative polymerase chain reaction. To determine the frequencies of our strains in nature, their multilocus sequence types were matched to published data sets. For the infected mice, 56.6% of the tissues were infected with B. burgdorferi. The mean spirochete load in the mouse necropsy tissues varied 4.8‐fold between the strains. The mean spirochete load in the ear tissue biopsies decreased rapidly over time for some strains. The percentage of infected tissues in male mice (65.4%) was significantly higher compared to female mice (50.5%). The mean spirochete load in the seven tissues was 1.5× higher in male mice compared to female mice; this male bias was 15.3× higher in the ventral skin. Across the 11 strains, the mean spirochete loads in the infected mouse tissues were positively correlated with the strain‐specific frequencies in their tick vector populations. The study suggests that laboratory‐based estimates of pathogen abundance in host tissues can predict the strain composition of this important tick‐borne pathogen in nature. [ABSTRACT FROM AUTHOR]

The causative bacterium of Lyme disease, Borrelia burgdorferi, expanded from an undetected human pathogen into the etiologic agent of the most common vector‐borne disease in the United States over the last several decades. Systematic field collections of the tick vector reveal increases in the geographic range and prevalence of B. burgdorferi–infected ticks that coincided with increases in human Lyme disease incidence across New York State.We investigate the impact of environmental features on the population dynamics of B. burgdorferi. Analytical models developed using field collections of nearly 19,000 nymphal Ixodes scapularis and spatially and temporally explicit environmental features accurately explained the variation in the nymphal infection prevalence of B. burgdorferi across space and time.Importantly, the model identified environmental features reflecting landscape ecology, vertebrate hosts, climatic metrics, climate anomalies and surveillance efforts that can be used to predict the biogeographical patterns of B. burgdorferi–infected ticks into future years and in previously unsampled areas.Forecasting the distribution and prevalence of a pathogen at fine geographic scales offers a powerful strategy to mitigate a serious public health threat.Synthesis and applications. A decade of environmental and tick data was collected to create a model that accurately predicts the infection prevalence of Borrelia burgdorferi over space and time. This predictive model can be extrapolated to create a high‐resolution risk map of the Lyme disease pathogen for future years that offers an inexpensive approach to improve both ecological management and public health strategies to mitigate disease risk. [ABSTRACT FROM AUTHOR]

Lyme disease, the most commonly reported vector‐borne disease in the United States, is caused by the bacteria Borrelia burgdorferi and is transmitted through the bite of an infected blacklegged tick. In the absence of a licensed vaccine, the prevention of Lyme disease relies heavily on limiting tick exposure. Methods for limiting tick exposure include personal protection measures such as repellent use, wearing protective clothing, avoiding areas where ticks may be present, bathing after exposure to tick habitat and performing regular tick checks. Public health officials typically recommend all these personal protection measures; however, there is limited evidence to promote one behaviour or practice over another. The focus of this article is to review available literature that examines the effectiveness of recommended personal protection measures to prevent Lyme and other Ixodes‐transmitted diseases in humans. Articles included in this review were identified through Google Scholar and PubMed searches using specific search terms. We identified over 56,000 articles using Google Scholar and PubMed searches. Of those, 16 studies fit our criteria for inclusion and were reviewed in their entirety. Among the personal protection measures evaluated, no intervention was predominantly or consistently effective across studies, demonstrating that, currently, there is no single best method for primary prevention of Ixodes‐transmitted diseases in the United States. Frequently recommended practices such as tick checks, repellent use and protective clothing had mixed results across studies. Study design differences limited comparability among studies, and sample sizes for these studies may have been too small to detect statistically significant results even if a prevention method was effective. Though many of the reviewed personal protection measures are frequently recommended to the public, limited evidence demonstrates their ability to prevent tick‐borne disease. Additional standardized studies are needed to evaluate personal protection measures. [ABSTRACT FROM AUTHOR]

The Lyme disease agent, Borrelia burgdorferi, harbors a significantly reduced genome and relies on the scavenging of critical nutrients from its tick and mammalian hosts for survival. Riboflavin salvage has been shown to be important for B. burgdorferi infection of mice, yet the contributions of riboflavin to B. burgdorferi metabolism and survival in the tick remain unknown. Using a targeted mass spectrometry approach, we confirmed the importance of bb0318, the putative ATPase component of an ABC‐type riboflavin transporter, for riboflavin salvage and the production of FMN and FAD. This analysis further revealed that Δbb0318 B. burgdorferi displayed increased levels of glycerol 3‐phosphate compared to the wild‐type. The glycerol 3‐phosphate dehydrogenase activity of GlpD was found to be FAD‐dependent and the transcription and translation of glpD were significantly decreased in Δbb0318 B. burgdorferi. Finally, gene bb0318 was found to be important for maximal spirochete burden in unfed larvae and essential for survival in feeding ticks. Together, these data demonstrate the importance of riboflavin salvage for B. burgdorferi carbon metabolism and survival in ticks. [ABSTRACT FROM AUTHOR]

To better understand vector‐borne disease dynamics, knowledge of the ecological interactions between animal hosts, vectors, and pathogens is needed. The effects of hosts on disease hazard depends on their role in driving vector abundance and their ability to transmit pathogens. Theoretically, a host that cannot transmit a pathogen could dilute pathogen prevalence but increase disease hazard if it increases vector population size. In the case of Lyme disease, caused by Borrelia burgdorferi s.l. and vectored by Ixodid ticks, deer may have dual opposing effects on vectors and pathogen: deer drive tick population densities but do not transmit B. burgdorferi s.l. and could thus decrease or increase disease hazard. We aimed to test for the role of deer in shaping Lyme disease hazard by using a wide range of deer densities while taking transmission host abundance into account. We predicted that deer increase nymphal tick abundance while reducing pathogen prevalence. The resulting impact of deer on disease hazard will depend on the relative strengths of these opposing effects. We conducted a cross‐sectional survey across 24 woodlands in Scotland between 2017 and 2019, estimating host (deer, rodents) abundance, questing Ixodes ricinus nymph density, and B. burgdorferi s.l. prevalence at each site. As predicted, deer density was positively associated with nymph density and negatively with nymphal infection prevalence. Overall, these two opposite effects canceled each other out: Lyme disease hazard did not vary with increasing deer density. This demonstrates that, across a wide range of deer and rodent densities, the role of deer in amplifying tick densities cancels their effect of reducing pathogen prevalence. We demonstrate how noncompetent host density has little effect on disease hazard even though they reduce pathogen prevalence, because of their role in increasing vector populations. These results have implications for informing disease mitigation strategies, especially through host management. [ABSTRACT FROM AUTHOR]

The density of Borrelia burgdorferi‐infected Ixodes ricinus nymphs (DIN) was investigated during 2013–2017 across a Lyme disease‐endemic landscape in southern England. The density of nymphs (DON), nymph infection prevalence (NIP), and DIN varied across five different natural habitats, with the highest DIN in woodland edge and high biodiversity woodlands. DIN was significantly lower in scrub grassland compared to the woodland edge, with low DON and no evidence of infection in ticks in non‐scrub grassland. Over the 5 years, DON, NIP and DIN were comparable within habitats, except in 2014, with NIP varying three‐fold and DIN significantly lower compared to 2015–2017. Borrelia garinii was most common, with bird‐associated Borrelia (B. garinii/valaisiana) accounting for ~70% of all typed sequences. Borrelia burgdorferi sensu stricto was more common than B. afzelii. Borrelia afzelii was more common in scrub grassland than woodland and absent in some years. The possible impact of scrub on grazed grassland, management of ecotonal woodland margins with public access, and the possible role of birds/gamebirds impacting NIP are discussed. Mean NIP was 7.6%, highlighting the potential risk posed by B. burgdorferi in this endemic area. There is a need for continued research to understand its complex ecology and identify strategies for minimizing risk to public health, through habitat/game management and public awareness. [ABSTRACT FROM AUTHOR]

M23 family endopeptidases play important roles in cell division and separation in a wide variety of bacteria. Recent studies have suggested that these proteins also contribute to bacterial virulence. However, the biological function of M23 peptidases in pathogenic spirochetes remains unexplored. Here, we describe Borrelia burgdorferi, the bacterial pathogen causing Lyme disease, requires a putative M23 family homolog, BB0761, for spirochete morphology and cell division. Indeed, the inactivation of bb0761 led to an aberrant filamentous phenotype as well as the impairment of B. burgdorferi growth in vitro. These phenotypes were complemented not only with B. burgdorferi bb0761, but also with the mepM gene from E. coli. Moreover, the bb0761 mutant showed a complete loss of infectivity in a murine model of Lyme borreliosis. Resistance of the mutant to osmotic and oxidative stresses was markedly reduced. Our combined results indicate that BB0761 contributes to B. burgdorferi cell division and virulence. [ABSTRACT FROM AUTHOR]

A vector's susceptibility and ability to transmit a pathogen—termed vector competency—determines disease outcomes, yet the ecological factors influencing tick vector competency remain largely unknown. Ixodes pacificus, the tick vector of Borrelia burgdorferi (Bb) in the western U.S., feeds on rodents, birds, and lizards. Rodents and birds are reservoirs for Bb and infect juvenile ticks, while lizards are refractory to Bb and cannot infect feeding ticks. Additionally, the lizard bloodmeal contains borreliacidal properties, clearing previously infected feeding ticks of their Bb infection. Despite I. pacificus feeding on a range of hosts, it is undetermined how the host identity of the larval bloodmeal affects future nymphal vector competency. We experimentally evaluate the influence of larval host bloodmeal on Bb acquisition by nymphal I. pacificus. Larval I. pacificus were fed on either lizards or mice and after molting, nymphs were fed on Bb‐infected mice. We found that lizard‐fed larvae were significantly more likely to become infected with Bb during their next bloodmeal than mouse‐fed larvae. We also conducted the first RNA‐seq analysis on whole‐bodied I. pacificus and found significant upregulation of tick antioxidants and antimicrobial peptides in the lizard‐fed group. Our results indicate that the lizard bloodmeal significantly alters vector competency and gene regulation in ticks, highlighting the importance of host bloodmeal identity in vector‐borne disease transmission and upends prior notions about the role of lizards in Lyme disease community ecology. [ABSTRACT FROM AUTHOR]

The zoonotic Lyme neuroborreliosis (LNB) disease is caused by Borrelia burgdorferi, with wide distribution, rapid dissemination and high disability rate. However, the molecular mechanism underlying B. burgdorferi mediated neuroborreliosis remains largely unknown. Here, the frontal cortex from rhesus brains was incubated with B. burgdorferi, and proteomics profiling was evaluated by isobaric tag for relative and absolute quantitation. Proteins were identified and quantified, and differentially expressed proteins (DEPs) were isolated by comparing co‐cultured samples and control samples. A total of 43, 164 and 368 DEPs were significantly altered after 6, 12 and 24 h treatment with B. burgdorferi respectively. Gene ontology and KEGG pathway analyses revealed that chemokine biological process was significantly enriched. Two genes in chemokine pathway including GRB2 and ROCK2 were significantly up‐regulated after B. burgdorferi co‐culturing. By in vitro assay, we confirmed that the expression of GRB2 and ROCK2 was increased after B. burgdorferi infection. In conclusion, our study revealed the involvement of chemokine pathway in the pathogenesis of LNB. GRB2 and ROCK2 may be novel biomarkers and therapeutic targets for LNB. [ABSTRACT FROM AUTHOR]

Background: Climate change, the increase of travel with infected animals from endemic areas, the introduction of new vectors in these areas and environmental changes caused by human activity, among other factors, have contributed to the establishment and increase of canine vector‐borne diseases (CVBDs), several of which are zoonotic and pose a risk to the human population. In Colombia, there are very few studies that address the prevalence of these diseases. The objective of this study was to update the prevalence of cardiopulmonary dirofilariosis, anaplasmosis, ehrlichiosis and Lyme borreliosis in dogs in Barranquilla and Puerto Colombia, areas of northern Colombia. Materials and methods: The present study included 354 dogs presented to veterinary clinics for routine health examination and foundations for stray dogs between November 2016 and July 2018. Results: The percentage of dogs positive for Ehrlichia spp. was 61.86%, followed by 22.03% for Anaplasma spp., 11.30% positive for Dirofilaria immitis antigens and 0.56% positive for Borrelia burgdorferi. In addition, several dogs positive for antibodies against two or more infectious diseases were found. Higher seroprevalences were documented in outdoor dogs compared to indoor‐housed dogs. Conclusion: These results suggest that veterinarians should routinely implement prophylactic programmes for these CVBDs, particularly for dogs that reside outdoors. [ABSTRACT FROM AUTHOR]

To determine Borrelia spp. (Spirochaetales: Spirochaetaceae) prevalence and species distribution in Northern Germany, Ixodes ticks were sampled from April to October in 2018 and 2019 by the flagging method at three locations each in five regions. Analysis by quantitative real‐time PCR of 3150 individual ticks revealed an overall prevalence of 30.6%, without significant differences between tick stages (31.7% positive adults, 28.6% positive nymphs). Significant differences were observed in seasonal infection rates, but not between regions, landscape types or sampling years. Analysis of co‐infections with Rickettsiales indicated a negative association between Borrelia and Anaplasma phagocytophilum infection. The most frequent Borrelia species differentiated by Reverse Line Blot were B. afzelii and B. garinii/B. bavariensis, followed by B. valaisiana, B. burgdorferi sensu stricto, B. spielmanii and B. lusitaniae. Furthermore, B. miyamotoi was identified in 12.9% of differentiable samples. No effect of region nor landscape type on species composition was found, but significant variations in the distribution at the different sampling sites within a region were observed. The detected monthly fluctuations in prevalence and the differences in intra‐regional Borrelia species distribution underline the importance of long‐term and multi‐location monitoring of Borrelia spp. in ticks as an essential part of public health assessment. [ABSTRACT FROM AUTHOR]

Morgellons disease (MD) is a rare dermatopathy characterized by nonspecific symptoms and the production of multicolored fibers and granular tissue from diffuse skin ulcerations which are described as being either pruritic or painful. The etiology of MD is currently unknown; previous studies have suggested both psychiatric and infectious causes, with increasing interest over the previous decade in elaborating a possible pathogenesis for the disease secondary to infection by Borrelia species. We report a middle‐aged Caucasian female who developed symptoms of MD in the days following exposure to a tick bite after spending an afternoon hiking through a wooded area. She was subsequently treated with a course of Doxycycline and found on two‐week follow‐up to have complete remission of her symptoms. This case report further supports the theory for an infectious etiology of MD and encourages future studies into its pathophysiology. [ABSTRACT FROM AUTHOR]

Keywords: adult; borrelia burgdorferi; facial hemiatrophy/aetiology; facial hemiatrophy/diagnosis; female; Lyme disease; syndrome EN adult borrelia burgdorferi facial hemiatrophy/aetiology facial hemiatrophy/diagnosis female Lyme disease syndrome e392 e394 3 11/14/22 20221101 NES 221101 Parry-Romberg syndrome (PRS) or progressive hemifacial atrophy was first described in 1825. This report intends to shine a light on the possibility of the coexistence of Lyme disease and the development of Parry-Romberg syndrome at older age. Adult, borrelia burgdorferi, female, Lyme disease, syndrome, facial hemiatrophy/aetiology, facial hemiatrophy/diagnosis. [Extracted from the article]