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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. Case report and literature review. 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. 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. [ABSTRACT FROM AUTHOR]

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 twostep 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 highendemic setting, characterized by high background seropositivity of about 50% and disease prevalence of approximately 10%, antibody tests are unable to rulein 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. [ABSTRACT FROM AUTHOR]

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.

Females often have chromatic patterns that differ from those of males. The evolution and function of female coloration is less known than those of males. Female ornaments can result from non-adaptive intersexual genetic correlation, but they may also signal female quality, health state, or potential fecundity. We examined whether the spectral characteristics of the sexually dichromatic coloration of female Iberian green lizards (Lacerta schreiberi) correlate with their condition, parasite load (ticks, hemoparasites and Borrelia infection) and the inflammatory response, and predict reproductive investment and offspring quality. Females with more intense UV-blue throat structural coloration and with more intense carotenoid-dependent yellow chests had less hemoparasites, and females with more saturated green dorsal coloration had lower tick loads. Also, females with greener backs seemed less prone to Borrelia burgdorferi s. l. infection. Surprisingly, in females not infected with Borrelia, there was a negative relationship between tick load and carotenoid content in the chest, which was not obvious in infected females. Characteristics of the females' coloration may also predict several variables of reproductive investment, such as egg laying date, incubation time, hatchling number, hatching success, and body size and condition of their hatchlings. Because this is a polygynandric species and mating investment is costly for males, we suggest that males might use female coloration to select potential mates. However, we can expect that the physiological basis of coloration is similar in both sexes and, therefore, genetic correlation and sexual selection may act synergistically. Significance statement: Despite widespread misconception that males are brightly colored and females are dull, females of some species also signal their quality with colorful ornaments. However, the function of female coloration is less often studied, although it may be important to fully understand sexual selection. Coloration of female Iberian green lizards is not so bright as that of males, but spectral characteristics of female colors can reflect body condition, parasite load, and immune response and, moreover, predict the number and quality of her future offspring. These correlations might help males to choose among female partners when selecting a good mate is a time and energy demanding task, increasing males' fitness. This would support direct sexual selection of female ornaments. [ABSTRACT FROM AUTHOR]

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]

Background: This study investigated Borrelia species prevalence in ticks from vegetation, through a molecular method, in Gwangju Metropolitan City, South Korea. Methodology/Principal findings: A total of 484 ticks were collected through flagging and dragging in a suburban area of Gwangju Metropolitan City, South Korea, in 2014. These ticks were morphologically identified and subjected to nested PCR, targeting Borrelia–specific CTP synthase (pyrG), outer surface protein A (ospA) and flagellin (flaB) genes. Molecular biological species identification of Borrelia-positive ticks was conducted via 16S rRNA PCR assays. Of the 484 ticks collected, 417 (86.2%) were identified as Haemaphysalis longicornis, 42 (8.7%) as H. flava, and 25 (5.2%) as Ixodes nipponensis. All the ixodid ticks containing Borrelia species bacteria were confirmed to be I. nipponensis adults, by both morphological and molecular methods. Of the 25 I. nipponensis ticks collected, four (16%) were positive for Borrelia species, three of which were B. afzelii and one B. miyamotoi. Conclusions/Significance: Our study has shown the harboring of B. miyamotoi by I. nipponensis in South Korea. Morphological and molecular genetic analyses revealed that, in South Korea, I. nipponensis could potentially transmit B. miyamotoi to humans. [ABSTRACT FROM AUTHOR]

The spirochetal bacterium Borrelia miyamotoi is a human pathogen and has been identified in many countries throughout the world. This study reports for the first time the presence of Borrelia miyamotoi in Ireland, and confirms prior work with the detection of B. garinii and B. valaisiana infected ticks. Questing Ixodes ricinus nymph samples were taken at six localities within Ireland. DNA extraction followed by Sanger sequencing was used to identify the species and strains present in each tick. The overall rate of borrelial infection in the Irish tick population was 5%, with a range from 2% to 12% depending on the locations of tick collection. The most prevalent species detected was B. garinii (70%) followed by B. valaisiana (20%) and B. miyamotoi (10%). Knowledge of Borrelia species prevalence is important and will guide appropriate selection of antigens for serology test kit manufacture, help define the risk of infection, and allow medical authorities to formulate appropriate strategies and guidelines for diagnosis and treatment of Borrelia diseases. [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]

Background: In low elevation arid regions throughout the Southern United States, Borrelia turicatae is the principal agent of tick-borne relapsing fever. However, endemic foci and the vertebrate hosts involved in the ecology of B. turicatae remain undefined. Experimental infection studies suggest that small and medium sized mammals likely maintain B. turicatae in nature, while the tick vector is a long-lived reservoir. Methodology/principal findings: Serum samples from wild caught rodents, raccoons, and wild and domestic canids from 23 counties in Texas were screened for prior exposure to B. turicatae. Serological assays were performed using B. turicatae protein lysates and recombinant Borrelia immunogenic protein A (rBipA), a diagnostic protein that is unique to RF spirochetes and may be a species-specific antigen. Conclusions/significance: Serological responses to B. turicatae were detected from 24 coyotes, one gray fox, two raccoons, and one rodent from six counties in Texas. These studies indicate that wild canids and raccoons were exposed to B. turicatae and are likely involved in the pathogen’s ecology. Additionally, more work should focus on evaluating rodent exposure to B. turicatae and the role of these small mammals in the pathogen’s maintenance in nature. [ABSTRACT FROM AUTHOR]

Objectives: Although statins have anti-inflammatory and potentially also antimicrobial (including antiviral) activity, their therapeutic impact on infectious diseases is controversial. In this study, we evaluated whether pre-existing statin use influenced the course and outcome of tick-borne encephalitis. Methods: To assess the influence of statin usage on the severity of acute illness and the outcome of tick-borne encephalitis, univariate and multivariable analyses were performed for 700 adult patients with tick-borne encephalitis of whom 77 (11%) were being treated with statins, and for 410 patients of whom 53 (13%) were receiving statins, respectively. Results: Multivariable analyses found no statistically significant association between statin usage and having a milder acute illness. There was also no statistically significant benefit with respect to a favorable outcome defined by the absence of post-encephalitic syndrome (ORs for a favorable outcome at 6 months was 0.96, 95% CI: 0.46–2.04, P = 0.926; at 12 months 0.29, 95% CI: 0.06–1.33, P = 0.111; at 2–7 years after acute illness 0.44, 95% CI: 0.09–2.22, P = 0.321), by a reduction in the frequency of six nonspecific symptoms (fatigue, myalgia/arthralgia memory disturbances, headache, concentration disturbances, irritability) occurring during the 4 week period before the last examination, or by higher SF-36 scores in any of the eight separate domains of health as well as in the physical and mental global overall component. Furthermore, there were no significant differences between patients receiving statins and those who were not in the cerebrospinal fluid or serum levels for any of the 24 cytokines/chemokines measured. Conclusions: In this observational study, we could not prove that pre-existing use of statins affected either the severity of the acute illness or the long-term outcome of tick-borne encephalitis. [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]

Borrelia burgdorferi, the causative agent of Lyme disease, is a vector-borne bacterial infection that is transmitted through the bite of an infected tick. If not treated with antibiotics during the early stages of infection, disseminated infection can spread to the central nervous system (CNS). In non-human primates (NHPs) it has been demonstrated that the leptomeninges are among the tissues colonized by B. burgdorferi spirochetes. Although the NHP model parallels aspects of human borreliosis, a small rodent model would be ideal to study the trafficking of spirochetes and immune cells into the CNS. Here we show that during early and late disseminated infection, B. burgdorferi infects the meninges of intradermally infected mice, and is associated with concurrent increases in meningeal T cells. We found that the dura mater was consistently culture positive for spirochetes in transcardially perfused mice, independent of the strain of B. burgdorferi used. Within the dura mater, spirochetes were preferentially located in vascular regions, but were also present in perivascular, and extravascular regions, as late as 75 days post-infection. At the same end-point, we observed significant increases in the number of CD3+ T cells within the pia and dura mater, as compared to controls. Flow cytometric analysis of leukocytes isolated from the dura mater revealed that CD3+ cell populations were comprised of both CD4 and CD8 T cells. Overall, our data demonstrate that similarly to infection in peripheral tissues, spirochetes adhere to the dura mater during disseminated infection, and are associated with increases in the number of meningeal T cells. Collectively, our results demonstrate that there are aspects of B. burgdorferi meningeal infection that can be modelled in laboratory mice, suggesting that mice may be useful for elucidating mechanisms of meningeal pathogenesis by B. burgdorferi. [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]

Background: Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has recently emerged in the field of entomology as a promising method for the identification of arthropods and the detection of associated pathogens. Methodology/Principal findings: An experimental model of Ctenocephalides felis (cat fleas) infected with Bartonella quintana and Bartonella henselae was developed to evaluate the efficacy of MALDI-TOF MS in distinguishing infected from uninfected fleas, and its ability to distinguish fleas infected with Bartonella quintana from fleas infected with Bartonella henselae. For B. quintana, two groups of fleas received three successive blood meals, infected or not. A total of 140 fleas (100 exposed fleas and 40 control fleas) were engorged on human blood, infected or uninfected with B. quintana. Regarding the second pathogen, two groups of fleas (200 exposed fleas and 40 control fleas) were fed in the same manner with human blood, infected or not with Bartonella henselae. Fleas were dissected longitudinally; one-half was used for assessment of B. quintana and B. henselae infectious status by real-time PCR, and the second half was subjected to MALDI-TOF MS analysis. Comparison of MS spectra from infected fleas and uninfected fleas revealed distinct MS profiles. Blind queries against our MALDI-TOF MS arthropod database, upgraded with reference spectra from B. quintana and B. henselae and infected but also non-infected fleas, provided the correct classification for 100% of the different categories of specimens tested on the first model of flea infection with Bartonella quintana. As for Bartonella henselae, 81% of exposed positive fleas, 96% of exposed negative fleas and 100% of control fleas were correctly identified on the second model of flea infection. MALDI-TOF MS successfully differentiated Bartonella spp.-infected and uninfected fleas and was also able to correctly differentiate fleas infected with Bartonella quintana and fleas infected with Bartonella henselae. MALDI-TOF MS correctly identified flea species as well as their infectious status, consistent with the results of real-time PCR. Conclusions/Significance: MALDI-TOF is a promising tool for identification of the infection status of fleas infected with Bartonella spp., which allows new possibilities for fast and accurate diagnosis in medical entomology and vector surveillance. [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]

California, with 13 chipmunk (Tamias) species, has more than any other state or country, occupying habitats ranging from chaparral to the high peaks of the Sierra Nevada. Chipmunks host zoonotic pathogens including Yersinia pestis, Anaplasma phagocytophilum, relapsing fever (RF) Borrelia spp., Borrelia burgdorferi, and spotted fever group (SFG) Rickettsia species. Chipmunk species are often not differentiated by public health workers, yet different species utilize different ecological niches and may have intrinsically different capacities for maintaining vector-borne pathogens and infecting vectors. We surveyed over 700 individuals from nine species of chipmunks throughout California for exposure to and infection by Y. pestis, A. phagocytophilum, RF Borrelia spp., Borrelia burgdorferi, and SFG Rickettsia species. DNA of all five pathogens was found and all chipmunks except Merriam’s chipmunk (T. merriami) were PCR-positive for at least one of the pathogens. Anaplasma phagocytophilum was most common (40.0%, 2/5) in Sonoma chipmunks (T. sonomae) from Marin county and B. burgdorferi most common (37.5%, 27/72) in redwood chipmunks (T. ochrogenys) from Mendocino county. RF Borrelia spp. was detected in 2% (6/297) of redwood chipmunks in Mendocino county and 10% (1/10) of both least (T. minimus) and lodgepole (T. speciosus) chipmunks in the western Sierra. Exposure to SFG Rickettsia spp. was found in the Northern Coastal region (Del Norte, Humboldt and Mendocino counties) and in the northern and western Sierra in several species of chipmunks. Y. pestis infection was found only in the western Sierra—in a yellow-pine (T. amoenus) and a long-eared (T. quadrimaculatus) chipmunk. Though more data are needed to thoroughly understand the roles that different chipmunk species play in disease transmission, our findings suggest that some chipmunk species may be more important to the maintenance of vector-borne diseases than others within each geographic area. [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]

Complement is an important part of innate immunity. The alternative pathway of complement is activated when the main opsonin, C3b coats non-protected surfaces leading to opsonisation, phagocytosis and cell lysis. The alternative pathway is tightly controlled to prevent autoactivation towards host cells. The main regulator of the alternative pathway is factor H (FH), a soluble glycoprotein that terminates complement activation in multiple ways. FH recognizes host cell surfaces via domains 19–20 (FH19-20). All microbes including Borrelia burgdorferi, the causative agent of Lyme borreliosis, must evade complement activation to allow the infectious agent to survive in its host. One major mechanism that Borrelia uses is to recruit FH from host. Several outer surface proteins (Osp) have been described to bind FH via the C-terminus, and OspE is one of them. Here we report the structure of the tripartite complex formed by OspE, FH19-20 and C3dg at 3.18 Å, showing that OspE and C3dg can bind simultaneously to FH19-20. This verifies that FH19-20 interacts via the “common microbial binding site” on domain 20 with OspE and simultaneously and independently via domain 19 with C3dg. The spatial organization of the tripartite complex explains how OspE on the bacterial surface binds FH19-20, leaving FH fully available to protect the bacteria against complement. Additionally, formation of tripartite complex between FH, microbial protein and C3dg might enable enhanced protection, particularly on those regions on the bacteria where previous complement activation led to deposition of C3d. This might be especially important for slow-growing bacteria that cause chronic disease like Borrelia burgdorferi. [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]

Background: Argasid ticks (soft ticks) are blood-feeding arthropods that can parasitize rodents, birds, humans, livestock and companion animals. Ticks of the Ornithodoros genus are known to be vectors of relapsing fever borreliosis in humans. In Algeria, little is known about relapsing fever borreliosis and other bacterial pathogens transmitted by argasid ticks. Methodology/Principal findings: Between May 2013 and October 2015, we investigated the presence of soft ticks in 20 rodent burrows, 10 yellow-legged gull (Larus michahellis) nests and animal shelters in six locations in two different bioclimatic zones in Algeria. Six species of argasid ticks were identified morphologically and through 16S rRNA gene sequencing. The presence and prevalence of Borrelia spp., Bartonella spp., Rickettsia spp. and Anaplasmataceae was assessed by qPCR template assays in each specimen. All qPCR-positive samples were confirmed by standard PCR, followed by sequencing the amplified fragments. Two Borrelia species were identified: Borrelia hispanica in Ornithodoros occidentalis in Mostaganem, and Borrelia cf. turicatae in Carios capensis in Algiers. One new Bartonella genotype and one new Anaplasmataceae genotype were also identified in Argas persicus. Conclusions: The present study highlights the presence of relapsing fever borreliosis agents, although this disease is rarely diagnosed in Algeria. Other bacteria of unknown pathogenicity detected in argasid ticks which may bite humans deserve further investigation. [ABSTRACT FROM AUTHOR]

Background: An association between tick bites, the development of immunoglobulin E (IgE) antibodies to galactose-α-1, 3-galactose (α-Gal) and red meat allergy has recently been reported. Here we wanted to elucidate the relation between tick exposure, IgE antibodies to α-Gal and Lyme borreliosis (LB). Methods: In the highly LB endemic area of Kalmar County, Sweden, serum samples and health inquiries from 518 blood donors were included. All sera were investigated for multiple IgG anti-Borrelia antibodies using a multiplex assay (recomBead, Mikrogen). In addition, three serially collected sera over a six month period from 148 patients with clinically defined erythema migrans (EM) were included. IgE antibodies against α-Gal were determined using ImmunoCAP (Thermo Fisher Scientific). Results: In blood donors reporting previous LB (n = 124) IgE to α-Gal was found in 16%, while in donors denying previous LB but with multiple anti-Borrelia antibodies (n = 94; interpreted as asymptomatic LB) 10% were IgE α-Gal-positive. Finally, in donors without Borrelia antibodies denying previous LB (n = 300) 14% showed IgE to α-Gal. No significant difference in proportions among the groups were found. In EM patients, IgE to α-Gal was found in 32/148 (22%) at diagnosis, 31/148 (21%) after two-three months and 23/148 (16%) after six months. A significant reduction of proportion and level of IgE to α-Gal was found between the second and third sample (p<0.01). A positive IgE anti α-Gal was more common among men compared with women both in blood donors and in EM patients (p≤0.01). Conclusions: IgE to α-Gal reactivity was common in a tick endemic area but showed no significant relation to previous LB. IgE anti-α-Gal reactivity in EM patients peaked within three months of diagnosis of EM, after which it waned indicating that recent tick exposure is of importance in α-Gal sensitization. Furthermore, IgE anti α-Gal was more common in men compared with women. [ABSTRACT FROM AUTHOR]

Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has been demonstrated to be useful for tick identification at the species level. More recently, this tool has been successfully applied for the detection of bacterial pathogens directly in tick vectors. The present work has assessed the detection of Borrelia burgdorferi sensu lato in Ixodes ricinus tick vector by MALDI-TOF MS. To this aim, experimental infection model of I. ricinus ticks by B. afzelii was carried out and specimens collected in the field were also included in the study. Borrelia infectious status of I. ricinus ticks was molecularly controlled using half-idiosome to classify specimens. Among the 39 ticks engorged on infected mice, 14 were confirmed to be infected by B. afzelii. For field collection, 14.8% (n = 12/81) I. ricinus ticks were validated molecularly as infected by B. burgdorferi sl. To determine the body part allowing the detection of MS protein profile changes between non-infected and B. afzelii infected specimens, ticks were dissected in three compartments (i.e. 4 legs, capitulum and half-idiosome) prior to MS analysis. Highly reproducible MS spectra were obtained for I. ricinus ticks according to the compartment tested and their infectious status. However, no MS profile change was found when paired body part comparison between non-infected and B. afzelii infected specimens was made. Statistical analyses did not succeed to discover, per body part, specific MS peaks distinguishing Borrelia-infected from non-infected ticks whatever their origins, laboratory reared or field collected. Despite the unsuccessful of MALDI-TOF MS to classify tick specimens according to their B. afzelii infectious status, this proteomic tool remains a promising method for rapid, economic and accurate identification of tick species. Moreover, the singularity of MS spectra between legs and half-idiosome of I. ricinus could be used to reinforce this proteomic identification by submission of both these compartments to MS. [ABSTRACT FROM AUTHOR]

We have previously shown that the Outer surface protein A (OspA) based Lyme borreliosis vaccine VLA15 induces protective immunity in mice. Herein, we report the induction of protective immunity by VLA15 with mouse models using ticks infected with B. burgdorferi (OspA serotype 1), B. afzelii (OspA serotype 2) and B. bavariensis (OspA serotype 4) or with in vitro grown B. garinii (OspA serotype 5 and 6) for challenge. For B. garinii (OspA serotype 3), we have developed a growth inhibition assay using chicken complement and functional antibodies targeting B. garinii (OspA serotype 3) could be demonstrated after immunization with VLA15. Furthermore, following three priming immunizations, a booster dose was administered five months later and the induction of immunological memory could be confirmed. Thus, the antibody titers after the booster dose were increased considerably compared to those after primary immunization. In addition, the half-lives of anti-OspA serotype specific antibodies after administration of the booster immunization were longer than after primary immunization. Taken together, we could show that VLA15 induced protection in mice against challenge with four different clinically relevant Borrelia species (B. burgdorferi, B. afzelii, B. garinii and B. bavariensis) expressing five of the six OspA serotypes included in the vaccine. The protection data is supported by functional assays showing efficacy against spirochetes expressing any of the six OspA serotypes (1 to 6). To our knowledge, this is the first time a Lyme borreliosis vaccine has been able to demonstrate such broad protection in preclinical studies. These new data provide further promise for the clinical development of VLA15 and supports our efforts to provide a new Lyme borreliosis vaccine available for global use. [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]

Lyme Borreliosis is an infectious disease caused by the spirochete Borrelia burgdorferi that is transmitted through the bite of infected ticks. Both B cell-mediated humoral immunity and T cell immunity develop during natural Borrelia infection. However, compared with humoral immunity, the T cell response to Borrelia infection has not been well elucidated. In this study, a novel T cell-based assay was developed and validated for the sensitive detection of antigen-specific T cell response to B. burgdorferi. Using interferon-g as a biomarker, we developed a new enzyme-linked immunospot method (iSpot Lyme™) to detect Borrelia antigen-specific effector/memory T cells that were activated in vivo by exposing them to recombinant Borrelia antigens ex vivo. To test this new method as a potential laboratory diagnostic tool, we performed a clinical study with a cohort of Borrelia positive patients and healthy controls. We demonstrated that the iSpot Lyme assay has a significantly higher specificity and sensitivity compared with the Western Blot assay that is currently used as a diagnostic measure. A comprehensive evaluation of the T cell response to Borrelia infection should, therefore, provide new insights into the pathogenesis, diagnosis, treatment and monitoring of Lyme disease.

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]