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Background: It is extremely rare for Lyme borreliosis to present solely with features of increased intracranial pressure. The treatment of pediatric Lyme neuroborreliosis with oral versus intravenous antibiotics remains controversial., Methods: Case report and literature review., Results: A 13-year-old male presented with five days of binocular diplopia, several weeks of headache, and a history of multiple tick bites six weeks prior. His examination showed a left eye abduction deficit and bilateral optic disc edema. Magnetic resonance imaging (MRI) of the brain with contrast showed tortuosity of the optic nerves, prominence of the optic nerve sheaths, and enhancement of the left fifth and bilateral sixth cranial nerves. Lumbar puncture showed an elevated opening pressure and a lymphocytic pleocytosis. Lyme IgM and IgG antibodies were positive in the serum and cerebrospinal fluid. The patient was treated with intravenous ceftriaxone for two days empirically followed by doxycycline by mouth for 19 days. Symptoms began improving after 48 hours. The strabismus resolved after two weeks, and the papilledema improved slowly with complete resolution at six months., Conclusions: Lyme neuroborreliosis can present as isolated intracranial hypertension in the pediatric population; it can be differentiated from idiopathic intracranial hypertension on MRI, and lumbar puncture and can be confirmed with serum antibody testing. Oral doxycycline can be considered for Lyme neuroborreliosis in children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The tick-borne multisystemic infection caused by Borrelia burgdorferi sensu lato , Lyme borreliosis, or Lyme disease, occurring in temperate regions of the northern hemisphere, continues to spread geographically with the expanding tick population. Despite the rising perceived risk of infection in the population, the clinical diagnosis of Borrelia infection is not always obvious and the most important laboratory test, antibody detection, has limited accuracy in diagnosing active disease. According to international guidelines, the primary serology test, which has a high sensitivity-low specificity, should, be verified using a high specificity confirmation test to improve the specificity. However, this enhancement in specificity comes at the cost of lower sensitivity. This two-step procedure is often omitted in everyday clinical practice. An optimal primary test would be one where no secondary tests for confirmation would be necessary. In the present study, the performance of a novel assay for quantitating IgG1-subclass antibodies to Borrelia C6-peptide was compared to a commercial reference assay of total IgG and IgM antibodies to Borrelia C6-peptide in the setting of a high endemic area for borreliosis. A derivation study on a retrospective clinical material was performed to compare the performance parameters and assess the discriminatory properties of the assays, followed by a prospective validation study. The IgG1-antibody assay achieved comparable summary performance parameters to those of the reference assay. The sensitivity was almost 100% while the specificity was about 50%. In a high-endemic setting, characterized by high background seropositivity of about 50% and disease prevalence of approximately 10%, antibody tests are unable to rule-in active Borrelia infection. The rule-out assessment of the methods revealed that of 1000 patients, 7 - 54 with negative results based on the reference method could have an active Borrelia infection. Such uncertainty was not found for the index test and may help improve the risk classification of patients., Competing Interests: DN, SO, and S-AC are partners in the Bimelix Laboratory. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nyman, Nordberg, Nyberg, Olausson, Carlströmer Berthen and Carlsson.)

Lyme disease is a common tick-borne infection caused by Borrelia burgdorferi in the United States, where infection is most prevalent in the northeastern and mid-Atlantic states. Although classically associated with erythema migrans, Lyme disease caused by Borrelia species found in Europe may also present with other cutaneous findings. Here we report the case of a girl who was clinically diagnosed with Lyme disease based on her history of recent travel and the appearance of an areolar lymphocytoma; this was confirmed by testing. Testing for European Lyme disease does not follow the testing algorithm that the Centers for Disease Control and Prevention recommends and may be easily missed. Our case serves as an important reminder that common infections can have varying presentations depending on their region of acquisition and may require specialized testing for accurate diagnosis., (© 2017 Wiley Periodicals, Inc.)

In a recent publication in PLOS ONE, Gabriele Margos and colleagues have questioned the division of the genus Borrelia into two genera on the basis that the differences in percentage of conserved proteins (POCP) between these two groups is >50%, which an earlier study has suggested as the threshold for differentiating prokaryotic genera. However, the POCP threshold is a poorly characterized and rarely used criterion for establishing distinction among prokaryotic genera. Detailed evaluation of the intergeneric POCP values for 37 genera from 3 different families (viz. Enterobacteriaceae- 24 genera, Morganellaceae-8 genera and Cystobacteraceae-5 genera) presented here shows that the POCP values for all genera within each of these families exceeded >58%. Thus, the suggested POCP threshold is not a useful criterion for delimitation of genus boundary and the objection by Margos et al. on this ground is invalid. Additionally, Margos et al. have questioned the specificities of ~15–20% of the conserved signature indels (CSIs) described in our work. However, as shown here, this concern is due to misunderstanding of the results and the CSIs in question are still highly-specific characteristics of the members of these genera and they provide important information regarding the evolutionary relationships of two new reptiles-echidna-related species viz. Borrelia turcica and Candidatus Borrelia tachyglossi to other Borrelia species. Results presented here show that both these species are deeper-branching members of the genus Borrelia and their placement within this genus is strongly supported by phylogenetic analyses and multiple uniquely shared CSIs with the other Borrelia species. Based on the large body of evidence derived from phylogenetic, genomic, molecular, phenotypic and clinical features, it is contended that the characteristics clearly distinguishing the Borrelia and Borreliella genera are far more numerous and of different kinds than those discerning most (all) other neighbouring genera of prokaryotes. Thus, the placement of these two groups of microorganisms into distinct genera, Borrelia and Borreliella, which clearly recognizes the differences among them, is highly appropriate and it should lead to a better understanding of the clinical, molecular and biological differences between these two important groups of microbes. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 45-year-old woman who was admitted for hospitalization after experiencing various symptoms including fever, arthralgias and diaphoresis. A retrospective evaluation of the patient's history was conducted and her clinical summary resulted with the suspicion of a tick-borne relapsing fever (TBRF) is offered. The serological analysis suggests that the patient was exposed to TBRF spirochetes through Borrelia turicatae.

The common human-biting tick, Ixodes pacificus, is the primary vector of the Lyme disease spirochete, Borrelia burgdorferi sensu stricto (ss) in western North America and has been found to harbor other closely-related spirochetes in the Borrelia burgdorferi sensu lato (sl) complex. Between 2008–2015, 11,066 adult and 3,815 nymphal I. pacificus and five adult and 144 nymphal Ixodes spinpalpis, a commonly collected wildlife tick, were collected from 42 California counties. Borrelia burgdorferi sl was detected in 1.2% and 3.8% I. pacificus adults and nymphs, respectively. Results from this study indicate genetic diversity and geographic structure of B. burgdorferi sl in California I. pacificus ticks, by sequence comparison of the16S rRNA gene, with B. burgdorferi ss, the agent of Lyme disease, found only in I. pacificus collected from the north and central coastal and Sierra Nevada foothill regions; B. burgdorferi ss was not detected in ticks tested from southern California. In contrast, Borrelia bissettiae, a member of the B. burgdorferi sl complex, was detected in both I. pacificus and I. spinipalpis, in the coastal region of both northern and southern California, but was absent from ticks in the Sierra Nevada foothills. In a similar pattern to B. bissettiae, Borrelia americana (a member of the B. burgdorferi sl complex) was detected in a single adult I. pacificus from the north coast and two I. spinipalpis nymphs from south-coastal California. This study highlights that the geographic area of Lyme disease acarological risk in California is the north-central and Sierra Nevada foothill regions of the state with little to no risk in the southern regions of the state. [ABSTRACT FROM AUTHOR]

Forests have become increasingly fragmented throughout the US, with residential development serving as the primary driver of these changes. These altered landscapes have provided suitable conditions for a broad range of wildlife, including blacklegged ticks and their hosts. Lawns dominate residential landscapes, and thus their management has the potential to reduce the likelihood of contact with ticks in residential yards. We tested the hypothesis that lawn mowing frequency influences tick occurrence in 16 suburban yards in Springfield, MA. We conducted 144 tick drags in lawns of various lawn mowing frequencies (mowed every week, every 2-weeks and every 3-weeks) and did not collect any ticks of any species. Promoting frequent mowing (i.e., shorter lawns) and the removal of grass clippings could have minimal impacts on tick microhabitats, but is consequential for beneficial wildlife and other ecosystem services associated with urban biodiversity. [ABSTRACT FROM AUTHOR]

The carboxy-terminal domain of the BBK32 protein from Borrelia burgdorferi sensu stricto, termed BBK32-C, binds and inhibits the initiating serine protease of the human classical complement pathway, C1r. In this study we investigated the function of BBK32 orthologues of the Lyme-associated Borrelia burgdorferi sensu lato complex, designated BAD16 from B. afzelii strain PGau and BGD19 from B. garinii strain IP90. Our data show that B. afzelii BAD16-C exhibits BBK32-C-like activities in all assays tested, including high-affinity binding to purified C1r protease and C1 complex, and potent inhibition of the classical complement pathway. Recombinant B. garinii BGD19-C also bound C1 and C1r with high-affinity yet exhibited significantly reduced in vitro complement inhibitory activities relative to BBK32-C or BAD16-C. Interestingly, natively produced BGD19 weakly recognized C1r relative to BBK32 and BAD16 and, unlike these proteins, BGD19 did not confer significant protection from serum killing. Site-directed mutagenesis was performed to convert BBK32-C to resemble BGD19-C at three residue positions that are identical between BBK32 and BAD16 but different in BGD19. The resulting chimeric protein was designated BXK32-C and this BBK32-C variant mimicked the properties observed for BGD19-C. To query the disparate complement inhibitory activities of BBK32 orthologues, the crystal structure of BBK32-C was solved to 1.7Å limiting resolution. BBK32-C adopts an anti-parallel four-helix bundle fold with a fifth alpha-helix protruding from the helical core. The structure revealed that the three residues targeted in the BXK32-C chimera are surface-exposed, further supporting their potential relevance in C1r binding and inhibition. Additional binding assays showed that BBK32-C only recognized C1r fragments containing the serine protease domain. The structure-function studies reported here improve our understanding of how BBK32 recognizes and inhibits C1r and provide new insight into complement evasion mechanisms of Lyme-associated spirochetes of the B. burgdorferi sensu lato complex. [ABSTRACT FROM AUTHOR]

Lyme disease, the most commonly reported vector-borne disease in North America, is caused by the spirochete Borrelia burgdorferi sensu stricto, which is transmitted by Ixodes scapularis in eastern Canada and Ixodes pacificus in western Canada. Recently, the northward range expansion of I. scapularis ticks, in south-eastern Canada, has resulted in a dramatic increase in the incidence of human Lyme disease. Detecting emerging areas of Lyme disease risk allows public health to target disease prevention efforts. We analysed passive tick surveillance data from Ontario and Manitoba to i) assess the relationship between the total numbers of I. scapularis submissions in passive surveillance from humans, and the number of human Lyme disease cases, and ii) develop province-specific acarological indicators of risk that can be used to generate surveillance-based risk maps. We also assessed associations between numbers of nymphal I. scapularis tick submissions only and Lyme disease case incidence. Using General Estimating Equation regression, the relationship between I. scapularis submissions (total numbers and numbers of nymphs only) in each census sub-division (CSD) and the number of reported Lyme disease cases was positively correlated and highly significant in the two provinces (P ≤ 0.001). The numbers of I. scapularis submissions over five years discriminated CSDs with ≥ 3 Lyme disease cases from those with < 3 cases with high accuracy when using total numbers of tick submission (Receiver Operating Characteristics area under the curve [AUC] = 0.89) and moderate accuracy (AUC = 0.78) when using nymphal tick submissions only. In Ontario the optimal cut-off point was a total 12 tick submissions from a CSD over five years (Sensitivity = 0.82, Specificity = 0.84), while in Manitoba the cut-off point was five ticks (Sensitivity = 0.71, Specificity = 0.79) suggesting regional variability of the risk of acquiring Lyme disease from an I. scapularis bite. The performances of the acarological indicators developed in this study for Ontario and Manitoba support the ability of passive tick surveillance to provide an early signal of the existence Lyme disease risk areas in regions where ticks and the pathogens they transmit are expanding their range. [ABSTRACT FROM AUTHOR]

Objectives: To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction. Methods: This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored. Results: 10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv. Conclusions: SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS. [ABSTRACT FROM AUTHOR]

As human cases of tick-borne disease continue to increase, there is a heightened imperative to collect data on human-tick encounters to inform disease prevention. Passive tick surveillance programs that encourage members of the public to submit ticks they have encountered can provide a relatively low-cost means of collecting such data. We report the results of 11 years of tick submissions (2006–2016) collected in Monmouth County, New Jersey, an Atlantic coastal county long endemic for Lyme disease. A total of 8,608 ticks acquired in 22 U.S. states were submitted, 89.7% of which were acquired in Monmouth County, from 52 of the County’s 53 municipalities. Seasonal submission rates reflected known phenology of common human-biting ticks, but annual submissions of both Amblyomma americanum and Dermacentor variabilis increased significantly over time while numbers of Ixodes scapularis remained static. By 2016, A. americanum had expanded northward in the county and now accounted for nearly half (48.1%) of submissions, far outpacing encounters with I. scapularis (28.2% of submissions). Across all tick species and stages the greatest number of ticks were removed from children (ages 0–9, 40.8%) and older adults (ages 50+, 23.8%) and these age groups were also more likely to submit partially or fully engorged ticks, suggesting increased risk of tick-borne disease transmission to these vulnerable age groups. Significantly more people (43.2%) reported acquiring ticks at their place of residence than in a park or natural area (17.9%). This pattern was more pronounced for residents over 60 years of age (72.7% acquired at home). Education that stresses frequent tick checks should target older age groups engaged in activity around the home. Our results strongly suggest that encounter rates with ticks other than I. scapularis are substantial and increasing and that their role in causing human illness should be carefully investigated. [ABSTRACT FROM AUTHOR]

Introduction: While Lyme disease (LD) is mostly treatable, misdiagnosed or untreated LD can result in debilitating sequelae and excessive healthcare usage. The objective of this review was to characterize the body of literature on the economic burden of Lyme disease (LD) and the cost-effectiveness of LD interventions, such as antibiotic treatment and vaccination. Methods: We followed Joanna Briggs Institute scoping review methodologies. We systematically searched terms related to LD, economic evaluations, costs, and cost-effectiveness in Medline, Embase, PsycInfo, Cochrane Library, and the grey literature up to November 2017. We included primary economic evaluations conducted in North America and Europe, reporting LD-related costs or cost-effectiveness of human interventions. Two reviewers screened articles and charted data independently. Costs were standardized to 2017 United States dollars (USD). Results: We screened 923 articles, and included 10 cost-effectiveness analyses (CEA) and 11 cost analyses (CA). Three CEAs concluded LD vaccination was likely cost-effective only in endemic areas (probability of infection ≥1%). However, LD vaccination is not currently available as an intervention in the US or Europe. Six studies assessed economic burden from a societal perspective and estimated significant annual national economic impact of: 735,550 USD for Scotland (0.14 USD per capita, population = 5.40M), 142,562 USD in Sweden (0.014 USD per capita, 9.96M), 40.88M USD in Germany (0.51 USD per capita, 80.59M), 23.12M USD in the Netherlands (1.36 USD per capita, 17.08M), and up to 786M USD in the US (2.41 USD per capita, 326.63M). Conclusions: Lyme disease imposes an economic burden that could be considered significant in the US and other developed countries to justify further research efforts in disease control and management. Societal costs for Lyme disease can be equally impactful as healthcare costs, but are not fully understood. Economic literature from countries with historically high incidence rates or increasing rates of Lyme disease are limited, and can be useful for future justification of resource allocation. [ABSTRACT FROM AUTHOR]

The genus Borrelia, originally described by Swellengrebel in 1907, contains tick- or louse-transmitted spirochetes belonging to the relapsing fever (RF) group of spirochetes, the Lyme borreliosis (LB) group of spirochetes and spirochetes that form intermittent clades. In 2014 it was proposed that the genus Borrelia should be separated into two genera; Borrelia Swellengrebel 1907 emend. Adeolu and Gupta 2014 containing RF spirochetes and Borreliella Adeolu and Gupta 2014 containing LB group of spirochetes. In this study we conducted an analysis based on a method that is suitable for bacterial genus demarcation, the percentage of conserved proteins (POCP). We included RF group species, LB group species and two species belonging to intermittent clades, Borrelia turcica Güner et al. 2004 and Candidatus Borrelia tachyglossi Loh et al. 2017. These analyses convincingly showed that all groups of spirochetes belong into one genus and we propose to emend, and re-unite all groups in, the genus Borrelia. [ABSTRACT FROM AUTHOR]

Lyme disease (LD), caused by bacteria of the Borrelia burgdorferi sensu lato species complex, is the most common vector-borne disease in North America and Europe. A systematic review (SR) was conducted to summarize the global literature on adverse birth outcomes associated with gestational LD in humans. The SR followed an a priori protocol of pretested screening, risk of bias, and data extraction forms. Data were summarized descriptively and random effects meta-analysis (MA) was used where appropriate. The SR identified 45 relevant studies, 29 describing 59 cases reported as gestational LD in the United States, Europe, and Asia (1969–2017). Adverse birth outcomes included spontaneous miscarriage or fetal death (n = 12), newborn death (n = 8), and newborns with an abnormal outcome (e.g. hyperbilirubinemia, respiratory distress and syndactyly) at birth (n = 16). Only one report provided a full case description (clinical manifestations in the mother, negative outcome for the child, and laboratory detection of B. burgdorferi in the child) that provides some evidence for vertical transmission of B. burgdorferi that has negative consequences for the fetus. The results of 17 epidemiological studies are included in this SR. Prevalence of adverse birth outcomes in an exposed population (defined by the authors as: gestational LD, history of LD, tick bites or residence in an endemic area) was compared to that in an unexposed population in eight studies and no difference was reported. A meta-analysis of nine studies showed significantly fewer adverse birth outcomes in women reported to have been treated for gestational LD (11%, 95%CI 7–16) compared to those who were not treated during pregnancy (50%, 95%CI 30–70) providing indirect evidence of an association between gestational LD and adverse birth outcomes. Other risk factors investigated; trimester of exposure, length of LD during pregnancy, acute vs. disseminated LD at diagnosis, and symptomatic LD vs. seropositive women with no LD symptoms during pregnancy were not significantly associated with adverse birth outcomes. This SR summarizes evidence from case studies that provide some limited evidence for transplacental transmission of B. burgdorferi. There was inconsistent evidence for adverse birth outcomes of gestational LD in the epidemiological research, and uncommon adverse outcomes for the fetus may occur as a consequence of gestational LD. The global evidence does not fully characterize the potential impact of gestational LD, and future research that addresses the knowledge gaps may change the findings in this SR. Given the current evidence; prompt diagnosis and treatment of LD during pregnancy is recommended. [ABSTRACT FROM AUTHOR]

Promoting health equity is a fundamental public health objective, yet health disparities remain largely overlooked in studies of vectorborne diseases, especially those transmitted by ticks. We sought to identify health disparities associated with Lyme disease and human monocytic ehrlichiosis, two of the most pervasive tickborne diseases within the United States. We used general linear mixed models to measure associations between county-level disease incidence and six variables representing racial/ethnic and socioeconomic characteristics of counties (percent white non-Hispanic; percent with a bachelors degree or higher; percent living below the poverty line; percent unemployed; percent of housing units vacant; per capita number of property crimes). Two ecological variables important to tick demography (percent forest cover; density of white-tailed deer) were included in secondary analyses to contextualize findings. Analyses included data from 2,695 counties in 37 states and the District of Columbia during 2007–2013. Each of the six variables was significantly associated with the incidence of one or both diseases, but the direction and magnitude of associations varied by disease. Results suggested that the incidence of Lyme disease was highest in counties with relatively higher proportions of white and more educated persons and lower poverty and crime rates; the incidence of human monocytic ehrlichiosis was highest in counties with relatively higher proportions of white and less educated persons, higher unemployment rates and lower crime rates. The percentage of housing units vacant was a strong positive predictor for both diseases with a magnitude of association comparable to those between incidence and the ecological variables. Our findings indicate that racial/ethnic and socioeconomic disparities in disease incidence appear to be epidemiologically important features of Lyme disease and human monocytic ehrlichiosis in the United States. Steps to mitigate encroachment of wild flora and fauna into areas with vacant housing might be warranted to reduce disease risk. [ABSTRACT FROM AUTHOR]

Elevated population levels of white-tailed deer (Odocoileus virginianus Zimmerman) can drastically alter forest ecosystems and negatively impact society through human interactions such as deer vehicle collisions. It is currently difficult to estimate deer populations at multiple scales ranging from stand, county, state, and regional levels. This presents a challenge as natural resource managers develop silvicultural prescriptions and forest management practices aimed at successfully regenerating tree species in the face of deer browsing. This study utilized measurements of deer browse impact from the new tree regeneration indicator developed by the United States Department of Agriculture Forest Service Forest Inventory and Analysis (FIA) program. Seedling and sapling abundance and other plot-level characteristics were analyzed across three states (Michigan, Minnesota, and Wisconsin) in the Great Lakes Region of the United States. Socio-environmental datasets (Lyme disease cases, deer vehicle collisions, and deer density estimates) were used in conjunction with FIA data to determine their predictive power in estimating deer browse impacts by county. Predictions from random forests models indicate that using Lyme disease case reports, the number of deer-vehicle collisions, deer density estimates, and forest inventory information correctly predicted deer browse impact 70–90% of the time. Deer-vehicle collisions per county ranked highly important in the random forests for predicting deer browse impacts in all three states. Lyme disease cases ranked high in importance for the Lake States combined and for Minnesota and Wisconsin, separately. Results show the effectiveness of predicting deer browse impacts using a suite of freely available forest inventory and other socio-environmental information. [ABSTRACT FROM AUTHOR]

In recent years, the number of Lyme disease or borreliosis cases in Eurasia has been dramatically increasing. This tick-borne disease is caused by Borrelia burgdorferi sensu lato, which includes B. burgdorferi sensu stricto, the main species found in North America, and B. afzelii and B. garinii, which are primarily responsible for the disease in Eurasia. Currently, research on Lyme disease has focused mainly on B. burgdorferi while B. afzelii and B. garinii, which cause disease with distinctly different symptoms, are less studied. The purpose of this study is to evaluate B. afzelii BO23 and B. garinii CIP 103362 as model organisms to study Eurasian Lyme disease. To begin our analyses, we sequenced, annotated the chromosomes of both species and compared them to B. burgdorferi strain B31. We also assayed shuttle vector, pBSV2, for transformation efficacy and demonstrated that these strains can be cultured on solid media. In addition, we characterized how physicochemical parameters (e.g., oxygen, osmolarity, oxidative stress) affect both growth and motility of the bacteria. Finally, we describe each strain’s antibiotic susceptibility and accessed their ability to infect mice. In conclusion, B. afzelii BO23 was more practical for in vitro and in vivo studies than B. garinii CIP 103362. [ABSTRACT FROM AUTHOR]

Lyme disease (LD) is the most common vector-borne disease in Ontario, Canada. We describe the epidemiology and clinical manifestations of LD in Ontario and examine trends in the incidence of non-disseminated and disseminated LD. LD surveillance data from the integrated Public Health Information System (iPHIS) from 2005–2014 were mapped to symptoms according to syndrome groups (erythema migrans (EM), flu-like, cardiac, neurologic or arthritic) and disease stages (early localized, early disseminated or late disseminated). During the study period, 1,230 cases due to Borrelia burgdoferi were reported in Ontario with annual incidence rates ranging from 0.32 (2006) to 2.16 (2013) cases per 100,000 population. Seventy percent of cases had EM and the proportion of cases with EM increased over time. Other clinical manifestations included flu-like (75%), arthritic (42%), neurologic (41%) and cardiac (6%) symptoms. Early localized disease (n = 415) manifested with EM (87%) and flu-like (57%) symptoms; early disseminated disease (n = 216) manifested with neurologic (94%), cardiac (10%) and EM (63%) symptoms; and late disseminated disease (n = 475) manifested with EM (62%), neurologic (55%), cardiac (9%), and arthritic symptoms (i.e., arthralgia (93%) and arthritis (7%)). Early localized and early disseminated cases (88% each) occurred primarily from May through September, compared to late disseminated cases (81%). The proportion of cases reported to public health within 30 days of illness onset increased during the study period, while the proportion of cases reported within 1–3 months and >3 months decreased. Geographical variations characterized by higher incidence of early localized disease and earlier public health notification (within 30 days of illness onset) occurred in regions with established or recently established LD risk areas, while later public health notification (>3 months after illness onset) was reported more frequently in regions with recently established or no identified risk areas. This is the first study to describe the clinical manifestations of LD in Ontario, Canada. The observed geographical variations in the epidemiology of LD in Ontario reinforce the need for regionally focused public health strategies aimed at increasing awareness, promoting earlier recognition and reporting, and encouraging greater uptake of preventive measures. [ABSTRACT FROM AUTHOR]

Background: Tick-borne infections have been increasing steadily over the years, with co-infections with Borrelia burgdorferi and Babesia microti/divergens emerging as a serious health problem. B. burgdorferi is a spirochetal bacterium that causes Lyme disease while protozoan pathogens belonging to Babesia species are responsible for babesiosis. Currently used serological tests do not always detect acute Lyme disease or babesiosis, and fail to differentiate cured patients from those who get re-infected. This is a major problem for proper diagnosis particularly in regions endemic for tick-borne diseases. Microscopy based evaluation of babesiosis is confirmatory but is labor intensive and insensitive such that many asymptomatic patients remain undetected and donate blood resulting in transfusion transmitted babesiosis. Results: We conducted multiplex qPCR for simultaneous diagnosis of active Lyme disease and babesiosis in 192 blood samples collected from a region endemic for both diseases. We document qPCR results obtained from testing of each sample three times to detect infection with each pathogen separately or together. Results for Lyme disease by qPCR were also compared with serological tests currently used for Lyme disease when available. Considering at least two out of three test results for consistency, 18.2% of patients tested positive for Lyme disease, 18.7% for co-infection with B. burgdorferi and B. microti and 6.3% showed only babesiosis. Conclusions: With an 80% sensitivity for detection of Lyme disease, and ability to detect co-infection with B. microti, multiplex qPCR can be employed for diagnosis of these diseases to start appropriate treatment in a timely manner. [ABSTRACT FROM AUTHOR]

Borrelia burgdorferi, the agent of Lyme borreliosis, can elude hosts’ innate and adaptive immunity as part of the course of infection. The ability of B. burgdorferi to invade or be internalized by host cells in vitro has been proposed as a mechanism for the pathogen to evade immune responses or antimicrobials. We have previously shown that B. burgdorferi can be internalized by human neuroglial cells. In this study we demonstrate that these cells take up B. burgdorferi via coiling phagocytosis mediated by the formin, Daam1, a process similarly described for human macrophages. Following coincubation with glial cells, B. burgdorferi was enwrapped by Daam1-enriched coiling pseudopods. Coiling of B. burgdorferi was significantly reduced when neuroglial cells were pretreated with anti-Daam1 antibody indicating the requirement for Daam1 for borrelial phagocytosis. Confocal microscopy showed Daam1 colocalizing to the B. burgdorferi surface suggesting interaction with borrelial membrane protein(s). Using the yeast 2-hybrid system for identifying protein-protein binding, we found that the B. burgdorferi surface lipoprotein, BBA66, bound the FH2 subunit domain of Daam1. Recombinant proteins were used to validate binding by ELISA, pull-down, and co-immunoprecipitation. Evidence for native Daam1 and BBA66 interaction was suggested by colocalization of the proteins in the course of borrelial capture by the Daam1-enriched pseudopodia. Additionally, we found a striking reduction in coiling for a BBA66-deficient mutant strain compared to BBA66-expressing strains. These results show that coiling phagocytosis is a mechanism for borrelial internalization by neuroglial cells mediated by Daam1. [ABSTRACT FROM AUTHOR]

The ecology of Lyme borreliosis is complex in northwestern California, with several potential reservoir hosts, tick vectors, and genospecies of Borrelia burgdorferi sensu lato. The primary objective of this study was to determine the fine-scale spatial distribution of different genospecies in four rodent species, the California ground squirrel (Otospermophilus beecheyi), northern flying squirrel (Glaucomys sabrinus), dusky-footed woodrat (Neotoma fuscipes), and Allen’s chipmunk (Neotamias senex). Rodents were live-trapped between June 2004 and May 2005 at the Hoopa Valley Tribal Reservation (HVTR) in Humboldt County, California. Ear-punch biopsies obtained from each rodent were tested by polymerase chain reaction (PCR) and sequencing analysis. The programs ArcGIS and SaTScan were used to examine the spatial distribution of genospecies. Multinomial log-linear models were used to model habitat and host-specific characteristics and their effect on the presence of each borrelial genospecies. The Akaike information criterion (AICc) was used to compare models and determine model fit. Borrelia burgdorferi sensu stricto was primarily associated with chipmunks and B. bissettiae largely with woodrats. The top model included the variables “host species”, “month”, and “elevation” (weight = 0.84). Spatial clustering of B. bissettiae was detected in the northwestern section of the HVTR, whereas B. burgdorferi sensu stricto was clustered in the southeastern section. We conclude that the spatial distribution of these borreliae are driven at least in part by host species, time-of-year, and elevation. [ABSTRACT FROM AUTHOR]

Lyme disease in humans is caused by several genospecies of the Borrelia burgdorferi sensu lato (s.l.) complex of spirochetal bacteria, including B. burgdorferi, B. afzelii and B. garinii. These bacteria exist in nature as obligate parasites in an enzootic cycle between small vertebrate hosts and Ixodid tick vectors, with humans representing incidental hosts. During the natural enzootic cycle, infected ticks in endemic areas feed not only upon naïve hosts, but also upon seropositive infected hosts. In the current study, we considered this environmental parameter and assessed the impact of the immune status of the blood-meal host on the phenotype of the Lyme disease spirochete within the tick vector. We found that blood from a seropositive host profoundly attenuates the infectivity (>104 fold) of homologous spirochetes within the tick vector without killing them. This dramatic neutralization of vector-borne spirochetes was not observed, however, when ticks and blood-meal hosts carried heterologous B. burgdorferi s.l. strains, or when mice lacking humoral immunity replaced wild-type mice as blood-meal hosts in similar experiments. Mechanistically, serum-mediated neutralization does not block induction of host-adapted OspC+ spirochetes during tick feeding, nor require tick midgut components. Significantly, this study demonstrates that strain-specific antibodies elicited by B. burgdorferi s.l. infection neutralize homologous bacteria within feeding ticks, before the Lyme disease spirochetes enter a host. The blood meal ingested from an infected host thereby prevents super-infection by homologous spirochetes, while facilitating transmission of heterologous B. burgdorferi s.l. strains. This finding suggests that Lyme disease spirochete diversity is stably maintained within endemic populations in local geographic regions through frequency-dependent selection of rare alleles of dominant polymorphic surface antigens. [ABSTRACT FROM AUTHOR]

Background: The treatment of persistent symptoms attributed to Lyme disease remains controversial. Recently, the PLEASE study did not demonstrate any additional clinical benefit of longer-term versus shorter-term antibiotic treatment. However, the economic impact of the antibiotic strategies has not been investigated. Methods: This prospective economic evaluation, adhering a societal perspective, was performed alongside the PLEASE study, a multicenter, placebo-controlled, double-blind 1:1:1 randomized clinical trial in which all patients received open-label intravenous ceftriaxone for two weeks before the 12-week randomized blinded oral antibiotic regimen (doxycycline, clarithromycin plus hydroxychloroquine, or placebo). Between 2010 and 2013, patients (n = 271) with borreliosis-attributed persistent symptoms were enrolled and followed for one year. Main outcomes were costs, quality-adjusted life years, and incremental net monetary benefit of longer-term versus shorter-term antibiotic therapy. Results: Mean quality-adjusted life years (95% CI) were not significantly different (p = 0.96): 0.82 (0.77–0.88) for ceftriaxone/doxycycline (n = 82), 0.81 (0.76–0.88) for ceftriaxone/clarithromycin-hydroxychloroquine (n = 93), and 0.81 (0.76–0.86) for ceftriaxone/placebo (n = 96). Total societal costs per patient (95% CI) were not significantly different either (p = 0.35): €11,995 (€8,823-€15,670) for ceftriaxone/doxycycline, €12,202 (€9,572-€15,253) for ceftriaxone/clarithromycin-hydroxychloroquine, and €15,249 (€11,294-€19,781) for ceftriaxone/placebo. Incremental net monetary benefit (95% CI) for ceftriaxone/doxycycline compared to ceftriaxone/placebo varied from €3,317 (-€2,199-€8,998) to €4,285 (-€6,085-€14,524) over the willingness-to-pay range, and that of ceftriaxone/clarithromycin-hydroxychloroquine compared to ceftriaxone/placebo from €3,098 (-€888-€7,172) to €3,710 (-€4,254-€11,651). For every willingness-to-pay threshold, the incremental net monetary benefits did not significantly differ from zero. Conclusion: The longer-term treatments were similar with regard to costs, effectiveness and cost-effectiveness compared to shorter-term treatment in patients with borreliosis-attributed persistent symptoms after one year of follow-up. Given the results of this study, and taking into account the external costs associated with antibiotic resistance, the shorter-term treatment is the antibiotic regimen of first choice. [ABSTRACT FROM AUTHOR]

To determine whether human Borrelia miyamotoi infection occurs in the far-western United States, we tested archived sera from northwestern California residents for antibodies to this emerging relapsing fever spirochete. These residents frequently were exposed to I. pacificus ticks in a region where B. miyamotoi tick infection has been reported. We used a two-step B. miyamotoi rGlpQ assay and a B. miyamotoi whole-cell lysate (WCL) assay to detect B. miyamotoi antibody. We also employed Borrelia hermsii and Borrelia burgdorferi WCL assays to examine if these Borrelia induce cross reacting antibody to B. miyamotoi. Sera were collected from 101 residents in each of two consecutive years. The sera of 12 and 14 residents in years one and two, respectively, were B. miyamotoi rGlpQ seroreactive. Sufficient sera were available to test 15 of the 26 seropositive samples using B. miyamotoi and B. hermsii WCL assays. Two residents in year one and seven residents in year two were seroreactive to both Borrelia antigens. Although discernible differences in seroreactivity were evident between the B. miyamotoi and B. hermsii WCL assays, infection with one or the other could not be determined with certainty. Sera from two Borrelia burgdorferi /B. miyamotoi seropositive subjects reacted strongly against B. miyamotoi and B. hermsii WCL antigens. Ecological, epidemiological, and clinical data implicated B. miyamotoi as the probable cause of infection among those whose sera reacted against both antigens. Our findings suggest that human B. miyamotoi infection occurs in northern California and that B. hermsii and B. burgdorferi infections produce antibodies that cross-react with B. miyamotoi antigens. Health care professionals in the far-western United States should be aware that B. miyamotoi disease may occur throughout the geographic distribution of I. pacificus and that improved relapsing fever group spirochete antibody assays are urgently needed. [ABSTRACT FROM AUTHOR]

Tick-Borne Relapsing Fever (TBRF) is caused by spirochetes in the genus Borrelia. Very limited information exists on the incidence of this disease in humans and domestic dogs in the United States. The main objective of this study is to evaluate exposure of dogs to Borrelia turicatae, a causative agent of TBRF, in Texas. To this end, 878 canine serum samples were submitted to Texas A&M Veterinary Medical Diagnostic Laboratory from October 2011 to September 2012 for suspected tick-borne illnesses. The recombinant Borrelial antigen glycerophosphodiester phosphodiesterase (GlpQ) was expressed, purified, and used as a diagnostic antigen in both ELISA assays and Immunoblot analysis. Unfortunately, due to significant background reaction, the use of GlpQ as a diagnostic marker in the ELISA assay was not effective in discriminating dogs exposed to B. turicatae. Nevertheless, immunoblot assays showed that 17 out of 853 samples tested were considered to be seropositive, which constitutes 1.99% of all Texas samples tested in this study. The majority of positive samples were from central and southern Texas. Exposure to TBRF spirochetes may be seasonal, with 70.59% (12 out of 17) of the cases detected between June and December. In addition, 2 out of the 17 sero-reactive cases (11.76%) showed reactivity to both B. burgdorferi (causative agent of Lyme disease) and B. turicatae (a causative agent of TBRF). This is the first report of TBRF sero-prevalence in companion animals in an endemic area. Our findings further indicate that B. turicatae is maintained in domestic canids in Texas in regions where human disease also occurs, suggesting that domestic dogs could serve as sentinels for this disease. [ABSTRACT FROM AUTHOR]

Previous studies have found that Met52®, which contains the entomopathogenic fungus Metarhizium brunneum, is effective in reducing the abundance of Ixodes scapularis, the tick vector for the bacterium causing Lyme disease and for other tick-borne pathogens. Given widespread interest in effective, safe methods for controlling ticks, Met52 has the potential to be used at increasing scales. The non-target impacts of Met52, as applied for tick control, have not yet been assessed. A Before-After-Control-Impact experiment was conducted to assess the effects of Met52 on non-target arthropods in lawn and forest habitats typical of residential yards. Ground-dwelling arthropods were collected using bulk sampling of soil and litter, and pitfall sampling. Arthropods were sampled once before and twice after treatment of plots with either Met52 or water (control). Multivariate general linear models were used to jointly model the abundance of arthropod orders. For each sampling method and post-spray sampling occasion, Akaike Information Criterion values were used to compare the fits of two alternative models: one that included effects of period (before vs. after spray), habitat (lawn vs. forest), and treatment (Met52 vs. control), versus a nested null model that included effects of period, and habitat, but no treatment effect. The null model was consistently better supported by the data. Significant effects were found of period and habitat but not treatment. Retrospective power analysis indicated the study had 80% power to detect a 50% reduction in arthropod abundance, as measured by bulk samples taken before versus one week after treatment. The deployment of Met52 in suburban settings is unlikely to cause meaningful reductions in the abundance of non-target arthropods. [ABSTRACT FROM AUTHOR]

Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. In Europe, it is transmitted by Ixodes ticks that carry bacteria belonging to the Borrelia burgdorferi sensu lato complex. The objective of this work was to explore eco-epidemiological factors of Lyme borreliosis in peri-urban forests of France (Sénart, Notre-Dame and Rambouillet). We investigated whether the introduction of Tamias sibiricus in Sénart could alter the density of infected ticks. Moreover, the density and tick infection were investigated according to the tree species found in various patches of Sénart forest. For this purpose, ticks were sampled during 3 years. In the Sénart forest, the density of nymph and adult ticks showed no significant difference between 2008, 2009 and 2011. The nymph density varied significantly as a function of the month of collection. Regarding the nymphs, a higher rate of infection and infected density were found in 2009. Plots with chipmunks (C) presented a lower density of both nymphs and adult ticks than plots without chipmunks (NC) did. A higher rate of infection of nymphs with Borrelia was seen in C plots. The prevalence of the various species of Borrelia was also found to vary between C and NC plots with the year of the collect. The presence of chestnut trees positively influenced the density of both nymphs and adults. The infected nymph density showed a significant difference depending on the peri-urban forest studied, Sénart being higher than Rambouillet. The prevalence of Borrelia species also differed between the various forests studied. Concerning the putative role that Tamias sibiricus may play in the transmission of Borrelia, our results suggest that its presence is correlated with a higher rate of infection of questing ticks by Borrelia genospecies and if its population increases, it could play a significant role in the risk of transmission of Lyme borreliosis. [ABSTRACT FROM AUTHOR]

Background: Understanding and quantification of the risk of Lyme borreliosis after a tick bite can aid development of prevention strategies against Lyme borreliosis. Methods: We used 3,525 single tick bite reports from three large prospective studies on the transmission risk of tick-borne pathogens to humans, with 50 reports of Lyme borreliosis during the follow-up period, among 1,973 reports with known outcome. A structural equation model was applied to estimate the risk of Lyme borreliosis after a tick bite, and quantify the influence of: developmental stage of the tick, detection of Borrelia burgdorferi s.l. DNA in the tick by PCR, tick engorgement, patient-estimated duration of tick attachment, and patient age. Results: The overall risk of developing Lyme borreliosis after a tick bite was 2.6% (95%CI 1.4–5.1). The risk increased with: The highest observed risk of Lyme borreliosis was 14.4% (95%CI 6.8%-24.6%) after one tick bite of a substantially engorged tick that tested positive for Borrelia burgdorferi s.l. DNA, which corresponds to one new case of Lyme borreliosis per 7 (95%CI 4–15) of such tick bites. Conclusions: An individual's risk of Lyme borreliosis after a tick bite can be predicted with tick engorgement, patient-estimated duration of tick attachment, and detection of Borrelia burgdorferi s.l. DNA in the tick. [ABSTRACT FROM AUTHOR]

This paper models the prevalence of antibodies to Borrelia burgdorferi in domestic dogs in the United States using climate, geographic, and societal factors. We then use this model to forecast the prevalence of antibodies to B. burgdorferi in dogs for 2016. The data available for this study consists of 11,937,925 B. burgdorferi serologic test results collected at the county level within the 48 contiguous United States from 2011-2015. Using the serologic data, a baseline B. burgdorferi antibody prevalence map was constructed through the use of spatial smoothing techniques after temporal aggregation; i.e., head-banging and Kriging. In addition, several covariates purported to be associated with B. burgdorferi prevalence were collected on the same spatio-temporal granularity, and include forestation, elevation, water coverage, temperature, relative humidity, precipitation, population density, and median household income. A Bayesian spatio-temporal conditional autoregressive (CAR) model was used to analyze these data, for the purposes of identifying significant risk factors and for constructing disease forecasts. The fidelity of the forecasting technique was assessed using historical data, and a Lyme disease forecast for dogs in 2016 was constructed. The correlation between the county level model and baseline B. burgdorferi antibody prevalence estimates from 2011 to 2015 is 0.894, illustrating that the Bayesian spatio-temporal CAR model provides a good fit to these data. The fidelity of the forecasting technique was assessed in the usual fashion; i.e., the 2011-2014 data was used to forecast the 2015 county level prevalence, with comparisons between observed and predicted being made. The weighted (to acknowledge sample size) correlation between 2015 county level observed prevalence and 2015 forecasted prevalence is 0.978. A forecast for the prevalence of B. burgdorferi antibodies in domestic dogs in 2016 is also provided. The forecast presented from this model can be used to alert veterinarians in areas likely to see above average B. burgdorferi antibody prevalence in dogs in the upcoming year. In addition, because dogs and humans can be exposed to ticks in similar habitats, these data may ultimately prove useful in predicting areas where human Lyme disease risk may emerge. [ABSTRACT FROM AUTHOR]

The genus Borrelia comprises arthropod-borne bacteria, which are infectious agents in vertebrates. They are mainly transmitted by ixodid or argasid ticks. In Hokkaido, Japan, Borrelia spp. were found in deer and Haemaphysalis ticks between 2011 and 2013; however, the study was limited to a particular area. Therefore, in the present study, we conducted large-scale surveillance of ticks and wild animals in the western part of the main island of Japan. We collected 6,407 host-seeking ticks from two regions and 1,598 larvae obtained from 32 engorged female ticks and examined them to elucidate transovarial transmission. In addition, we examined whole blood samples from 190 wild boars and 276 sika deer, as well as sera from 120 wild raccoons. We detected Borrelia spp. in Haemaphysalis flava, Haemaphysalis megaspinosa, Haemaphysalis kitaokai, Haemaphysalis longicornis, and Haemaphysalis formosensis. In addition, we isolated a strain from H. megaspinosa using Barbour-Stoenner-Kelly medium. The minimum infection rate of ticks was less than 5%. Transovarial transmission was observed in H. kitaokai. Phylogenetic analysis of the isolated strain and DNA fragments amplified from ticks identified at least four bacterial genotypes, which corresponded to the tick species detected. Bacteria were detected in 8.4%, 15%, and 0.8% of wild boars, sika deer, and raccoons, respectively. In this study, we found seasonal differences in the prevalence of bacterial genotypes in sika deer during the winter and summer. The tick activity season corresponds to the season with a high prevalence of animals. The present study suggests that a particular bacterial genotype detected in this study are defined by a particular tick species in which they are present. [ABSTRACT FROM AUTHOR]

Lyme disease is emerging in eastern and central Canada, and most cases are diagnosed using the two-tier serological test (Enzyme Immuno Assay [EIA] followed by Western blot [WB]). Simplification of this algorithm would be advantageous unless it impacts test performance. In this study, accuracy of individual proteins of the IgG WB algorithm in predicting the overall test result in samples from Canadians was assessed. Because Borrelia burgdorferi strains vary geographically in Canada, geographic variations in serological responses were also explored. Metrics of relative sensitivity, specificity and the kappa statistic measure of concordance were used to assess the capacity of responses to individual proteins to predict the overall IgG WB result of 2524 EIA (C6)-positive samples from across Canada. Geographic and interannual variations in proportions of samples testing positive were explored by logistic regression. No one protein was highly concordant with the IgG WB result. Significant variations were found amongst years and geographic regions in the prevalence of samples testing positive using the overall IgG WB algorithm, and for individual proteins of the algorithm. In most cases the prevalence of samples testing positive were highest in Nova Scotia, and lower in samples from Manitoba westwards. These findings suggest that the current two tier test may not be simplified and continued use of the current two-tier test method and interpretation is recommended. Geographic and interannual variations in the prevalence of samples testing positive may be consistent with B. burgdorferi strain variation in Canada, and further studies are needed to explore this. [ABSTRACT FROM AUTHOR]

The isolation of B. burgdorferi sensu lato requires the use of complex cultivation media. The aim of the study was to compare the usefulness of BSK-H (a commercial medium produced by HiMedia, India) and MKP medium. MKP and BSK-H media were prepared in accordance with the relevant protocols. Borrelia strains and skin culture biopsies were simultaneously inoculated into both media, incubated and checked for growth. Borrelial growth characteristics, isolation rates and characteristics of the isolated borreliae were analysed and compared. Initially, numbers of spirochaetes were higher in BSK-H than in MKP; however, in comparison with MKP, the strains subcultured in BSK-H medium were more frequently irregular, thin and non-motile, and rapidly died. In addition, the borrelial isolation rate from erythema migrans skin samples was higher in MKP than in BSK-H medium (108/171, 63.2% versus 70/171, 40.9%; p<0.0001). The far most frequently isolated species was Borrelia afzelii (92.9% and 97.2% strains isolated from BSK-H and MKP, respectively). Comparison of strains cultured from individual patients in both media showed differences in plasmid contents in 9/46 (19.6%) strain pairs, and protein profiles differed in 30/43 (69.8%) strain pairs, most often in the expression of OspC (in 27/28 patients OspC was expressed only in strains growing in MKP). BSK-H medium supports the growth of borrelial strains but MKP is superior with regard to the isolation rate, morphology and motility of strains. BSK-H medium supports fast initial growth of borreliae but this is followed by rapid deformation and death of the spirochaetes. [ABSTRACT FROM AUTHOR]

Lyme disease is caused by infection with the bacterium Borrelia burgdorferi (Bb), which is transmitted to humans by deer ticks. The infection manifests usually as a rash and minor systemic symptoms; however, the bacteria can spread to other tissues, causing joint pain, carditis, and neurological symptoms. Lyme neuroborreliosis presents itself in several ways, such as Bell’s palsy, meningitis, and encephalitis. The molecular basis for neuroborreliosis is poorly understood. Analysis of the changes in the expression levels of messenger RNAs and non-coding RNAs, including microRNAs, following Bb infection could therefore provide vital information on the pathogenesis and clinical symptoms of neuroborreliosis. To this end, we used cultured primary human astrocytes, key responders to CNS infection and important components of the blood-brain barrier, as a model system to study RNA and microRNA changes in the CNS caused by Bb. Using whole transcriptome RNA-seq, we found significant changes in 38 microRNAs and 275 mRNAs at 24 and 48 hours following Bb infection. Several of the RNA changes affect pathways involved in immune response, development, chromatin assembly (including histones) and cell adhesion. Further, several of the microRNA predicted target mRNAs were also differentially regulated. Overall, our results indicate that exposure to Bb causes significant changes to the transcriptome and microRNA profile of astrocytes, which has implications in the pathogenesis, and hence potential treatment strategies to combat this disease. [ABSTRACT FROM AUTHOR]

Lyme disease is a major vector-borne bacterial disease in the USA. The disease is caused by Borrelia burgdorferi, and transmitted among hosts and humans, primarily by blacklegged ticks (Ixodes scapularis). The ~25 B. burgdorferi genotypes, based on genotypic variation of their outer surface protein C (ospC), can be phenotypically separated as strains that primarily cause human diseases—human invasive strains (HIS)—or those that rarely do. Additionally, the genotypes are non-randomly associated with host species. The goal of this study was to examine the extent to which phenotypic outcomes of B. burgdorferi could be explained by the host communities fed upon by blacklegged ticks. In 2006 and 2009, we determined the host community composition based on abundance estimates of the vertebrate hosts, and collected host-seeking nymphal ticks in 2007 and 2010 to determine the ospC genotypes within infected ticks. We regressed instances of B. burgdorferi phenotypes on site-specific characteristics of host communities by constructing Bayesian hierarchical models that properly handled missing data. The models provided quantitative support for the relevance of host composition on Lyme disease risk pertaining to B. burgdorferi prevalence (i.e. overall nymphal infection prevalence, or NIPAll) and HIS prevalence among the infected ticks (NIPHIS). In each year, NIPAll and NIPHIS was found to be associated with host relative abundances and diversity. For mice and chipmunks, the association with NIPAll was positive, but tended to be negative with NIPHIS in both years. However, the direction of association between shrew relative abundance with NIPAll or NIPHIS differed across the two years. And, diversity (H') had a negative association with NIPAll, but positive association with NIPHIS in both years. Our analyses highlight that the relationships between the relative abundances of three primary hosts and the community diversity with NIPAll, and NIPHIS, are variable in time and space, and that disease risk inference, based on the role of host community, changes when we examine risk overall or at the phenotypic level. Our discussion focuses on the observed relationships between prevalence and host community characteristics and how they substantiate the ecological understanding of phenotypic Lyme disease risk. [ABSTRACT FROM AUTHOR]

A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography. [ABSTRACT FROM AUTHOR]

Recent reports suggest that host-seeking nymphs in southern populations of Ixodes scapularis remain below the leaf litter surface, while northern nymphs seek hosts on leaves and twigs above the litter surface. This behavioral difference potentially results in decreased tick contact with humans in the south, and fewer cases of Lyme disease. We studied whether north-south differences in tick survival patterns might contribute to this phenomenon. Four month old larvae resulting from a cross between Wisconsin males and South Carolina females died faster under southern than under northern conditions in the lab, as has previously been reported for ticks from both northern and southern populations. However, newly-emerged larvae from Rhode Island parents did not differ consistently in mortality under northern and southern conditions, possibly because of their younger age. Survival is lower, and so the north-south survival difference might be greater in older ticks. Larval survival was positively related to larval size (as measured by scutal area), while survival was positively related to larval fat content in some, but not all, trials. The difference in larval survival under northern vs. southern conditions might simply result from faster metabolism under warmer southern conditions leading to shorter life spans. However, ticks consistently died faster under southern than under northern conditions in the laboratory when relative humidity was low (75%), but not under moderate (85%) or high (95%) RH. Therefore, mortality due to desiccation stress is greater under southern than under northern conditions. We hypothesize that mortality resulting from the greater desiccation stress under southern conditions acts as a selective pressure resulting in the evolution of host-seeking behavior in which immatures remain below the leaf litter surface in southern I. scapularis populations, so as to avoid the desiccating conditions at the surface. If this hypothesis is correct, it has implications for the effect of climate change on the future distribution of Lyme disease. [ABSTRACT FROM AUTHOR]

Borrelia mayonii, a Borrelia burgdorferi sensu lato (Bbsl) genospecies, was recently identified as a cause of Lyme borreliosis (LB) among patients from the upper midwestern United States. By microscopy and PCR, spirochete/genome loads in infected patients were estimated at 105 to 106 per milliliter of blood. Here, we present the full chromosome and plasmid sequences of two B. mayonii isolates, MN14-1420 and MN14-1539, cultured from blood of two of these patients. Whole genome sequencing and assembly was conducted using PacBio long read sequencing (Pacific Biosciences RSII instrument) followed by hierarchical genome-assembly process (HGAP). The B. mayonii genome is ~1.31 Mbp in size (26.9% average GC content) and is comprised of a linear chromosome, 8 linear and 7 circular plasmids. Consistent with its taxonomic designation as a new Bbsl genospecies, the B. mayonii linear chromosome shares only 93.83% average nucleotide identity with other genospecies. Both B. mayonii genomes contain plasmids similar to B. burgdorferi sensu stricto lp54, lp36, lp28-3, lp28-4, lp25, lp17, lp5, 5 cp32s, cp26, and cp9. The vls locus present on lp28-10 of B. mayonii MN14-1420 is remarkably long, being comprised of 24 silent vls cassettes. Genetic differences between the two B. mayonii genomes are limited and include 15 single nucleotide variations as well as 7 fewer silent vls cassettes and a lack of the lp5 plasmid in MN14-1539. Notably, 68 homologs to proteins present in B. burgdorferi sensu stricto appear to be lacking from the B. mayonii genomes. These include the complement inhibitor, CspZ (BB_H06), the fibronectin binding protein, BB_K32, as well as multiple lipoproteins and proteins of unknown function. This study shows the utility of long read sequencing for full genome assembly of Bbsl genomes, identifies putative genome regions of B. mayonii that may be linked to clinical manifestation or tissue tropism, and provides a valuable resource for pathogenicity, diagnostic and vaccine studies. [ABSTRACT FROM AUTHOR]

There has been an increasing incidence of Lyme disease (LD) in Canada and the United States corresponding to the expanding range of the Ixodes tick vector and Lyme disease agent (Borrelia burgdorferi sensu stricto). There are many diagnostic tests for LD available in North America, all of which have some performance issues, and physicians are concerned about the appropriate use and interpretation of these tests. The objective of this systematic review is to summarize the North American evidence on the accuracy of diagnostic tests and test regimes at various stages of LD. Included in the review are 48 studies on diagnostic tests used in North America published since 1995. Thirteen studies examined a two-tier serological test protocol vs. clinical diagnosis, 24 studies examined single assays vs. clinical diagnosis, 9 studies examined single immunoblot vs. clinical diagnosis, 7 studies compared culture or PCR direct detection methods vs. clinical diagnosis, 22 studies compared two or more tests with each other and 8 studies compared a two-tiered serological test protocol to another test. Recent studies examining the sensitivity and specificity of various test protocols noted that the Immunetics® C6 B. burgdorferi ELISA™ and the two tier approach have superior specificity compared to proposed replacements, and the CDC recommended western blot algorithm has equivalent or superior specificity over other proposed test algorithms. There is a dramatic increase in test sensitivity with progression of B. burgdorferi infection from early to late LD. Direct detection methods, culture and PCR of tissue or blood samples were not as sensitive or timely compared to serological testing. It was also noted that there are a large number of both commercial (n = 42) and in-house developed tests used by private laboratories which have not been evaluated in the primary literature. [ABSTRACT FROM AUTHOR]

World-wide concern over emerging vector-borne diseases has increased in recent years for both animal and human health. In the United Sates, concern about vector-borne diseases in canines has focused on Lyme disease, anaplasmosis, ehrlichiosis, and heartworm which infect domestic and wild canids. Of these diseases, Lyme and anaplasmosis are also frequently diagnosed in humans. Gray wolves (Canis lupus) recolonized Wisconsin in the 1970s, and we evaluated their temporal and geographic patterns of exposure to these four vector-borne diseases in Wisconsin as the population expanded between 1985 and 2011. A high proportion of the Wisconsin wolves were exposed to the agents that cause Lyme (65.6%) and anaplasma (47.7%), and a smaller proportion to ehrlichiosis (5.7%) and infected with heartworm (9.2%). Wolf exposure to tick borne diseases was consistently higher in older animals. Wolf exposure was markedly higher than domestic dog (Canis familiaris) exposure for all 4 disease agents during 2001–2013. We found a cluster of wolf exposure to Borrelia burgdorferi in northwestern Wisconsin, which overlaps human and domestic dog clusters for the same pathogen. In addition, wolf exposure to Lyme disease in Wisconsin has increased, corresponding with the increasing human incidence of Lyme disease in a similar time period. Despite generally high prevalence of exposure none of these diseases appear to have slowed the growth of the Wisconsin wolf population. [ABSTRACT FROM AUTHOR]

Background: Tick-borne diseases are the most prevalent vector-borne diseases in Europe. Knowledge on the incidence and clinical presentation of other tick-borne diseases than Lyme borreliosis and tick-borne encephalitis is minimal, despite the high human exposure to these pathogens through tick bites. Using molecular detection techniques, the frequency of tick-borne infections after exposure through tick bites was estimated. Methods: Ticks, blood samples and questionnaires on health status were collected from patients that visited their general practitioner with a tick bite or erythema migrans in 2007 and 2008. The presence of several tick-borne pathogens in 314 ticks and 626 blood samples of this cohort were analyzed using PCR-based methods. Using multivariate logistic regression, associations were explored between pathogens detected in blood and self-reported symptoms at enrolment and during a three-month follow-up period. Results: Half of the ticks removed from humans tested positive for Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis, Rickettsia helvetica, Rickettsia monacensis, Borrelia miyamotoi and several Babesia species. Among 92 Borrelia burgdorferi s. l. positive ticks, 33% carried another pathogen from a different genus. In blood of sixteen out of 626 persons with tick bites or erythema migrans, DNA was detected from Candidatus Neoehrlichia mikurensis (n = 7), Anaplasma phagocytophilum (n = 5), Babesia divergens (n = 3), Borrelia miyamotoi (n = 1) and Borrelia burgdorferi s. l. (n = 1). None of these sixteen individuals reported any overt symptoms that would indicate a corresponding illness during the three-month follow-up period. No associations were found between the presence of pathogen DNA in blood and; self-reported symptoms, with pathogen DNA in the corresponding ticks (n = 8), reported tick attachment duration, tick engorgement, or antibiotic treatment at enrolment. Conclusions: Based on molecular detection techniques, the probability of infection with a tick-borne pathogen other than Lyme spirochetes after a tick bite is roughly 2.4%, in the Netherlands. Similarly, among patients with erythema migrans, the probability of a co-infection with another tick-borne pathogen is approximately 2.7%. How often these infections cause disease symptoms or to what extend co-infections affect the course of Lyme borreliosis needs further investigations. [ABSTRACT FROM AUTHOR]

In Lyme borreliosis, the skin is the key site for bacterial inoculation by the infected tick and for cutaneous manifestations. We previously showed that different strains of Borrelia burgdorferi sensu stricto isolated from tick and from different clinical stages of the Lyme borreliosis (erythema migrans, and acrodermatitis chronica atrophicans) elicited a very similar transcriptional response in normal human dermal fibroblasts. In this study, using whole transcriptome microarray chips, we aimed to compare the transcriptional response of normal human dermal fibroblasts stimulated by 3 Borrelia burgdorferi sensu lato strains belonging to 3 main pathogenic species (B. afzelii, B. garinii and B. burgdorferi sensu stricto) in order to determine whether “species-related” inflammatory pathways could be identified. The three Borrelia strains tested exhibited similar transcriptional profiles, and no species-specific fingerprint of transcriptional changes in fibroblasts was observed. Conversely, a common core of chemokines/cytokines (CCL2, CXCL1, CXCL2, CXCL6, CXCL10, IL-6, IL-8) and interferon-related genes was stimulated by all the 3 strains. Dermal fibroblasts appear to play a key role in the cutaneous infection with Borrelia, inducing a homogeneous inflammatory response, whichever Borrelia species was involved. [ABSTRACT FROM AUTHOR]

Lyme borreliosis is caused by the spirochete Borrelia burgdorferi sensu lato, a fastidious bacterium that replicates slowly and requires special conditions to grow in the laboratory. Borrelia isolation from clinical material is a golden standard for microbiological diagnosis of borrelial infection. Important factors that affect in vitro borrelia growth are temperature of incubation and number of borrelia cells in the sample. The aim of the study was to assess the influence of temperature on borrelia growth and survival by evaluation and comparison of growth of 31 different borrelia strains at five different temperatures and to determine the influence of different inoculums on borrelia growth at different temperatures. Borreliae were cultured in the MKP medium; the initial and final number of spirochetes was determined by dark field microscopy using Neubauer counting chamber. The growth of borrelia was defined as final number of cells/mL after three days of incubation. For all three Borrelia species, the best growth was found at 33°C, followed by 37, 28, and 23°C, while no growth was detected at 4°C (P<0.05). The growth of B. afzelii species was weaker in comparison to the other two species at 23, 28, 33 and 37°C (P<0.05), respectively. There was no statistically significant difference between the growth of B. garinii and B. burgdorferi sensu stricto at 28, 33, and 37°C (P>0.05), respectively. Inoculum had statistically significant influence on growth of all three Borrelia species at all tested temperatures except at 4°C. [ABSTRACT FROM AUTHOR]

Introduction: Ticks are the most common arthropod vectors of both human and animal diseases in Europe, and the Ixodes ricinus tick species is able to transmit a large number of bacteria, viruses and parasites. Ticks may also be co-infected with several pathogens, with a subsequent high likelihood of co-transmission to humans or animals. However few data exist regarding co-infection prevalences, and these studies only focus on certain well-known pathogens. In addition to pathogens, ticks also carry symbionts that may play important roles in tick biology, and could interfere with pathogen maintenance and transmission. In this study we evaluated the prevalence of 38 pathogens and four symbionts and their co-infection levels as well as possible interactions between pathogens, or between pathogens and symbionts. Methodology/principal findings: A total of 267 Ixodes ricinus female specimens were collected in the French Ardennes and analyzed by high-throughput real-time PCR for the presence of 37 pathogens (bacteria and parasites), by rRT-PCR to detect the presence of Tick-Borne encephalitis virus (TBEV) and by nested PCR to detect four symbionts. Possible multipartite interactions between pathogens, or between pathogens and symbionts were statistically evaluated. Among the infected ticks, 45% were co-infected, and carried up to five different pathogens. When adding symbiont prevalences, all ticks were infected by at least one microorganism, and up to eight microorganisms were identified in the same tick. When considering possible interactions between pathogens, the results suggested a strong association between Borrelia garinii and B. afzelii, whereas there were no significant interactions between symbionts and pathogens. Conclusion/significance: Our study reveals high pathogen co-infection rates in ticks, raising questions about possible co-transmission of these agents to humans or animals, and their consequences to human and animal health. We also demonstrated high prevalence rates of symbionts co-existing with pathogens, opening new avenues of enquiry regarding their effects on pathogen transmission and vector competence. [ABSTRACT FROM AUTHOR]

Based on chromosome sequences, the human pathogen Borrelia miyamotoi phylogenetically clusters with species that cause relapsing fever. But atypically for relapsing fever agents, B. miyamotoi is transmitted not by soft ticks but by hard ticks, which also are vectors of Lyme disease Borrelia species. To further assess the relationships of B. miyamotoi to species that cause relapsing fever, I investigated extrachromosomal sequences of a North American strain with specific attention on plasmid-borne vsp and vlp genes, which are the underpinnings of antigenic variation during relapsing fever. For a hybrid approach to achieve assemblies that spanned more than one of the paralogous vsp and vlp genes, a database of short-reads from next-generation sequencing was supplemented with long-reads obtained with real-time DNA sequencing from single polymerase molecules. This yielded three contigs of 31, 16, and 11 kb, which each contained multiple and diverse sequences that were homologous to vsp and vlp genes of the relapsing fever agent B. hermsii. Two plasmid fragments had coding sequences for plasmid partition proteins that differed from each other from paralogous proteins for the megaplasmid and a small plasmid of B. miyamotoi. One of 4 vsp genes, vsp1, was present at two loci, one of which was downstream of a candiate prokaryotic promoter. A limited RNA-seq analysis of a population growing in the blood of mice indicated that of the 4 different vsp genes vsp1 was the one that was expressed. The findings indicate that B. miyamotoi has at least four types of plasmids, two or more of which bear vsp and vlp gene sequences that are as numerous and diverse as those of relapsing fever Borrelia. The database and insights from these findings provide a foundation for further investigations of the immune responses to this pathogen and of the capability of B. miyamotoi for antigenic variation. [ABSTRACT FROM AUTHOR]