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The absence of a long COVID (LC) or post-acute sequelae of COVID-19 (PASC) diagnostic has profound implications for research and potential therapeutics given the lack of specificity with symptom-based identification of LC and the overlap of symptoms with other chronic inflammatory conditions. Here, we report a machine-learning approach to LC/PASC diagnosis on 347 individuals using cytokine hubs that are also capable of differentiating LC from chronic lyme disease (CLD). We derived decision tree, random forest, and gradient-boosting machine (GBM) classifiers and compared their diagnostic capabilities on a dataset partitioned into training (178 individuals) and evaluation (45 individuals) sets. The GBM model generated 89% sensitivity and 96% specificity for LC with no evidence of overfitting. We tested the GBM on an additional random dataset (106 LC/PASC and 18 Lyme), resulting in high sensitivity (97%) and specificity (90%) for LC. We constructed a Lyme Index confirmatory algorithm to discriminate LC and CLD. [ABSTRACT FROM AUTHOR]

Patients with post-treatment Lyme disease (PTLD) report negative perceptions of care and significant invalidation from medical professionals. However, the relationship of invalidation to illness severity has not been examined, nor have risk factors for invalidation been identified. This cross-sectional study enrolled 80 patients who met stringent criteria for PTLD. We examined correlations between the Illness Invalidation Inventory and measures of symptom severity, quality of life, and trust in physicians. To study the relationship between invalidation and potential demographic and clinical factors, we generated simple unadjusted and multivariate adjusted linear regression models. We found that higher 'lack of understanding' and 'discounting' subscale scores of the Illness Invalidation Inventory were significantly positively correlated with higher symptom severity, lower quality of life, and lower trust in physicians. In adjusted linear regression models, older age (lack of understanding: β = − 0.17, p = 0.008, discounting: β = − 0.19, p = 0.001, every 10 years) and male gender (lack of understanding: β = − 0.49, p = 0.016, discounting: β = − 0.51, p = 0.006) were associated with less invalidation. We also identified receiving an alternative diagnosis for PTLD as a mediator in the relationship between gender and invalidation. Based on our findings, we hypothesize that reducing invalidation within the clinical encounter could positively affect illness burden and quality of life for patients with PTLD. [ABSTRACT FROM AUTHOR]

Borrelia, spirochetes transmitted by ticks, are the etiological agents of numerous multisystemic diseases, such as Lyme borreliosis (LB) and tick-borne relapsing fever (TBRF). This study focuses on two surface proteins from two Borrelia subspecies involved in these diseases: CspZ, expressed by Borrelia burgdorferi sensu stricto (also named BbCRASP-2 for complement regulator-acquiring surface protein 2), and the factor H binding A (FhbA), expressed by Borrelia hermsii. Numerous subspecies of Borrelia, including these latter, are able to evade the immune defenses of a variety of potential vertebrate hosts in a number of ways. In this context, previous data suggested that both surface proteins play a role in the immune evasion of both Borrelia subspecies by interacting with key regulators of the alternative pathway of the human complement system, factor H (FH) and FH-like protein 1 (FHL-1). The recombinant proteins, CspZ and FhbA, were expressed in Escherichia coli and purified by one-step metal-affinity chromatography, with yields of 15 and 20 mg or pure protein for 1 L of cultured bacteria, respectively. The purity was evaluated by SDS-PAGE and HPLC and is close to about 95%. The mass of CspZ and FhbA was checked by mass spectrometry (MS). Proper folding of CspZ and FhbA was confirmed by circular dichroism (CD), and their biological activity, namely their interaction with purified FH from human serum (recombinant FH15-20 and recombinant FHL-1), was characterized by SPR. Such a study provides the basis for the biochemical characterization of the studied proteins and their biomolecular interactions which is a necessary prerequisite for the development of new approaches to improve the current diagnosis of LB and TBRF. Key points: • DLS, CD, SEC-MALS, NMR, HPLC, and MS are tools for protein quality assessment • Borrelia spp. possesses immune evasion mechanisms, including human host complement • CspZ and FhbA interact with high affinity (pM to nM) to human FH and rFHL-1 [ABSTRACT FROM AUTHOR]

The environmental risk of Lyme disease, defined by the density of Ixodes scapularis ticks and their prevalence of Borrelia burgdorferi infection, is increasing across the Ottawa, Ontario region, making this a unique location to explore the factors associated with environmental risk along a residential-woodland gradient. In this study, we collected I. scapularis ticks and trapped Peromyscus spp. mice, tested both for tick-borne pathogens, and monitored the intensity of foraging activity by deer in residential, woodland, and residential-woodland interface zones of four neighbourhoods. We constructed mixed-effect models to test for site-specific characteristics associated with densities of questing nymphal and adult ticks and the infection prevalence of nymphal and adult ticks. Compared to residential zones, we found a strong increasing gradient in tick density from interface to woodland zones, with 4 and 15 times as many nymphal ticks, respectively. Infection prevalence of nymphs and adults together was 15 to 24 times greater in non-residential zone habitats. Ecological site characteristics, including soil moisture, leaf litter depth, and understory density, were associated with variations in nymphal density and their infection prevalence. Our results suggest that high environmental risk bordering residential areas poses a concern for human-tick encounters, highlighting the need for targeted disease prevention. [ABSTRACT FROM AUTHOR]

Morgellons disease is characterized by the persistent delusion of skin infestation, ultimately inflicting wounds and impairing quality of life. There is insufficient and conflicting research pertaining to this condition, imposing challenges on clinicians in understanding, diagnosing, and treating it. In this review, we summarize the available literature on Morgellons disease including its historical evolution, epidemiology, proposed pathophysiology, underlying structural and functional brain pathologies, typical and atypical clinical presentations, diagnosis, and treatment. A comprehensive review of the literature was conducted on PubMed, Embase, and Scopus using specified keywords. Selected articles were screened by two independent reviewers based on set inclusion and exclusion criteria. Conflicts were resolved by a third reviewer as needed. No limit to the date of selected articles was set due to the scarce literature available on the subject. Morgellons disease is an underdiagnosed entity, owing mostly to the lack of an established pathophysiology and treatment guidelines. While many authors classify it as a type of delusional infestation (DI), others correlate MD with an underlying spirochetal infection, namely Lyme disease. Neuroimaging studies have revealed abnormalities in the "fronto-striato-thalamo-parietal network", a finding common to patients with DI, in addition to alterations in structures related to the "Itch Processing Pathway". Patients tend to extract fibers from their skin lesions and place them in a match box hence the term "match box sign". The diagnosis is that of exclusion, requiring extensive work up to rule out secondary causes and differential diagnoses. Treatment is largely based on the use of antipsychotics, with or without cognitive behavioral therapy. Despite being a diagnosis of exclusion, clinicians must be aware of this entity and have a profound understanding of the pathogenesis underlying it. Upon clinical suspicion, secondary Morgellons should always be ruled out through a thorough history taking, physical examination, and laboratory exams. Despite the challenges brought by the heterogeneous presentation of the condition and the paucity of research revolving around it, the great impact that Morgellons disease has on patients' quality of life forms a pressing need for its adequate detection, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Lyme disease, caused by a bacterium transmitted through the bite of an infected tick, is often misdiagnosed due to its similarity to other conditions like drug rash. This research introduces an innovative approach by integrating prominent deep learning models, including UNet, Inception Model, and XGBoost, into the Deep Neuro-Fuzzy System. Utilizing a comprehensive Kaggle dataset, authors study aims to achieve heightened accuracy in recognizing and segmenting Lyme disease from medical images. Implemented in Python, authors advanced image processing methods demonstrate exceptional performance, reaching an outstanding accuracy of 97.36% after the recognition stage. To further enhance accuracy, authors introduce an additional layer of sophistication through the incorporation of the mayfly optimization (MO) approach. This strategic integration of MO contributes to the outstanding accuracy achieved by their models. This research not only addresses the challenges of Lyme disease misdiagnosis but also presents a robust framework for medical image recognition. Leveraging the collaborative and open nature of Kaggle and the versatility of the Python programming ecosystem, authors work contributes to advancing the field of Lyme disease detection and medical image processing. [ABSTRACT FROM AUTHOR]

Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020–December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that affects mainly young people. It is believed that the autoimmune process observed in the pathogenesis of MS is influenced by a complex interaction between genetic and environmental factors, including infectious agents. The results of this study suggest the protective role of Toxoplasma gondii infections in MS. Interestingly, high Toxoplasma IgM seropositivity in MS patients receiving immunomodulatory drugs (IMDs) was identified. On the other hand, Borrelia infections seem to be positively associated with MS. Although the interpretation of our results is limited by the retrospective nature of the studies, the results strongly indicate that further experimental and clinical studies are needed to explain the role of infectious agents in the development and pathophysiological mechanisms of MS. [ABSTRACT FROM AUTHOR]

Lyme borreliosis (LB) is the most commonly diagnosed tick-borne disease in the northern hemisphere. Since an efficient vaccine is not yet available, prevention of transmission is essential. This, in turn, requires a thorough comprehension of the spatiotemporal dynamics of LB transmission as well as underlying drivers. This study aims to identify spatiotemporal trends and unravel environmental and socio-economic covariates of LB incidence in Poland, using consistent monitoring data from 2010 through 2019 obtained for 320 (aggregated) districts. Using yearly LB incidence values, we identified an overall increase in LB incidence from 2010 to 2019. Additionally, we observed a large variation of LB incidences between the Polish districts, with the highest risks of LB in the eastern districts. We applied spatiotemporal Bayesian models in an all-subsets modeling framework to evaluate potential associations between LB incidence and various potentially relevant environmental and socio-economic variables, including climatic conditions as well as characteristics of the vegetation and the density of tick host species. The best-supported spatiotemporal model identified positive relationships between LB incidence and forest cover, the share of parks and green areas, minimum monthly temperature, mean monthly precipitation, and gross primary productivity. A negative relationship was found with human population density. The findings of our study indicate that LB incidence in Poland might increase as a result of ongoing climate change, notably increases in minimum monthly temperature. Our results may aid in the development of targeted prevention strategies. [ABSTRACT FROM AUTHOR]

The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource. Common genetic variants can affect an individual's immune response to pathogens. Here, the authors uncover and characterize variants regulating cytokine responses in Lyme Borreliosis in 1,060 patients. [ABSTRACT FROM AUTHOR]

Objectives: To describe the course of symptoms reported by patients with symptoms attributed to Lyme borreliosis (LB) without being subsequently diagnosed with LB. Methods: We performed a prospective cohort study with patients presenting at the outpatient clinic of two clinical LB centres. The primary outcome was the prevalence of persistent symptoms, which were defined as clinically relevant fatigue (CIS, subscale fatigue), pain (SF-36, subscale bodily pain), and cognitive impairment (CFQ) for ≥ 6 months and onset < 6 months over the first year of follow-up. Outcomes were compared with a longitudinal cohort of confirmed LB patients and a general population cohort. Prevalences were standardised to the distribution of pre-defined confounders in the confirmed LB cohort. Results: Participants (n = 123) reported mostly fatigue, arthralgia, myalgia, and paraesthesia as symptoms. The primary outcome could be determined for 74.8% (92/123) of participants. The standardised prevalence of persistent symptoms in our participants was 58.6%, which was higher than in patients with confirmed LB at baseline (27.2%, p < 0.0001) and the population cohort (21.2%, p < 0.0001). Participants reported overall improvement of fatigue (p < 0.0001) and pain (p < 0.0001) but not for cognitive impairment (p = 0.062) during the follow-up, though symptom severity at the end of follow-up remained greater compared to confirmed LB patients (various comparisons p < 0.05). Conclusion: Patients with symptoms attributed to LB who present at clinical LB centres without physician-confirmed LB more often report persistent symptoms and report more severe symptoms compared to confirmed LB patients and a population cohort. [ABSTRACT FROM AUTHOR]

Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease. The genetic basis of susceptibility to Lyme disease is largely unknown. Here, the authors discover a risk locus in the gene encoding the protein Secretoglobin family 1D member 2, which is expressed in skin and affects infection by the bacteria that causes Lyme disease in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Uncovering the complexity of systems in non-model organisms is critical for understanding arthropod immunology. Prior efforts have mostly focused on Dipteran insects, which only account for a subset of existing arthropod species in nature. Here we use and develop advanced techniques to describe immune cells (hemocytes) from the clinically relevant tick Ixodes scapularis at a single-cell resolution. We observe molecular alterations in hemocytes upon feeding and infection with either the Lyme disease spirochete Borrelia burgdorferi or the rickettsial agent Anaplasma phagocytophilum. We reveal hemocyte clusters exhibiting defined signatures related to immunity, metabolism, and proliferation. Depletion of phagocytic hemocytes affects hemocytin and astakine levels, two I. scapularis hemocyte markers, impacting blood-feeding, molting behavior, and bacterial acquisition. Mechanistically, astakine alters hemocyte proliferation, whereas hemocytin affects the c-Jun N-terminal kinase (JNK) signaling pathway in I. scapularis. Altogether, we discover a role for tick hemocytes in immunophysiology and provide a valuable resource for comparative biology in arthropods. Rolandelli et al. define how immune cells from the tick Ixodes scapularis are affected by infection and show that this cell population have distinct signatures and functions in immunity, metabolism and proliferation. [ABSTRACT FROM AUTHOR]

This article discusses a case of meningoencephalitis and retinal vasculitis caused by a rickettsial infection. Rickettsia are bacteria that are transmitted through ectoparasites like ticks, fleas, mites, or lice. The patient in this case had recently traveled to Mexico and developed symptoms such as chest pain, abdominal pain, shortness of breath, headache, and meningism. The diagnosis was confirmed through positive serum results for rickettsia antibodies. The patient was treated with antibiotics and corticosteroids, and while there was improvement, the visual disturbances persisted. The article highlights the challenges in diagnosing rickettsial infections and the potential complications associated with them. [Extracted from the article]

Lyme disease is the most common vector-borne disease in the United States impacting the Northeast and Midwest at the highest rates. Recently, it has become established in southeastern and south-central regions of Canada. In these regions, Lyme disease is caused by Borrelia burgdorferi, which is transmitted to humans by an infected Ixodes scapularis tick. Understanding the parasite-host interaction is critical as the white-footed mouse is one of the most competent reservoir for B. burgdorferi. The cycle of infection is driven by tick larvae feeding on infected mice that molt into infected nymphs and then transmit the disease to another susceptible host such as mice or humans. Lyme disease in humans is generally caused by the bite of an infected nymph. The main aim of this investigation is to study how diapause delays and demographic and seasonal variability in tick births, deaths, and feedings impact the infection dynamics of the tick-mouse cycle. We model tick-mouse dynamics with fixed diapause delays and more realistic Erlang distributed delays through delay and ordinary differential equations (ODEs). To account for demographic and seasonal variability, the ODEs are generalized to a continuous-time Markov chain (CTMC). The basic reproduction number and parameter sensitivity analysis are computed for the ODEs. The CTMC is used to investigate the probability of Lyme disease emergence when ticks and mice are introduced, a few of which are infected. The probability of disease emergence is highly dependent on the time and the infected species introduced. Infected mice introduced during the summer season result in the highest probability of disease emergence. [ABSTRACT FROM AUTHOR]

Incidence of Lyme disease, a tick-borne illness prevalent in the US, is increasing in endemic regions and regions with no previous history of the disease, significantly impacting public health. We examined space–time patterns of Lyme disease incidence and the influence of ecological and social factors on spatial synchrony, i.e., correlated incidence fluctuations across US counties. Specifically, we addressed these questions: Does Lyme disease incidence exhibit spatial synchrony? If so, what geographic patterns does Lyme disease synchrony exhibit? Are geographic patterns of disease synchrony related to weather, land cover, access to health care, or tick-borne disease awareness? How do effects of these variables on Lyme disease synchrony differ geographically? We used network analysis and matrix regression to examine geographical patterns of Lyme disease synchrony and their potential mechanisms in 399 counties in the eastern and Midwestern US. We found two distinct regions of synchrony in Northeast and upper Midwest regions exhibiting opposing temporal fluctuations in incidence. Spatial patterns of Lyme disease synchrony were partly explained by land cover, weather, poverty, and awareness of tick-borne illness, with significant predictive variables changing regionally. However, the two regions may have become more synchronous over time, potentially leading to higher-amplitude nation-wide fluctuations in disease incidence. [ABSTRACT FROM AUTHOR]

Lyme disease (LD) is the most common vector-borne disease in the United States (U.S.). This paper assesses how climate change may influence LD incidence in the eastern and upper Midwestern U.S. and the associated economic burden. We estimated future Ixodes scapularis habitat suitability and LD incidence with a by-degree approach using variables from an ensemble of multiple climate models. We then applied estimates for present-day and projected habitat suitability for I. scapularis, present-day presence of Borrelia burgdorferi, and projected climatological variables to model reported LD incidence at the county level among adults, children, and the total population. Finally, we applied an estimate of healthcare expenses to project economic impacts. We show an overall increase in LD cases with regional variation. We estimate an increase in incidence in New England and the upper Midwestern U.S. and a concurrent decrease in incidence in Virginia and North Carolina. At 3°C of national warming from the 1986–2015 baseline climate, we project approximately 55,000 LD cases, a 38-percent increase from present-day estimates. At 6°C of warming, our most extreme scenario, we project approximately 92,000 LD cases in the region, an increase of 145 percent relative to current levels. Annual LD-related healthcare expenses at 3°C of warming are estimated to be $236 million (2021 dollars), approximately 38 percent greater than present-day. These results may inform decision-makers tasked with addressing climate risks, the public, and healthcare professionals preparing for treatment and prevention of LD. [ABSTRACT FROM AUTHOR]

Lyme disease diagnosis poses a significant challenge, with blood tests exhibiting an alarming inaccuracy rate of nearly 60% in detecting early-stage infections. As a result, there is an urgent need for improved diagnostic methods that can offer more accurate detection outcomes. To address this pressing issue, our study focuses on harnessing the potential of deep learning approaches, specifically by employing model pipelining through progressive resizing and multiple self-supervised learning models. In this paper, we present a comprehensive exploration of self-supervised learning models, including SimCLR, SwAV, MoCo, and BYOL, tailored to the context of Lyme disease detection using medical imaging. The effectiveness and performance of these models are evaluated using standard metrics such as F1 score, precision, recall, and accuracy. Furthermore, we emphasize the significance of progressive resizing and its implications when dealing with convolutional neural networks (CNNs) for medical image analysis. By leveraging deep learning approaches, progressive resizing, and self-supervised learning models, the challenges associated with Lyme disease detection are effectively addressed in this study. The application of our novel methodology and the execution of a comprehensive evaluation framework contribute invaluable insights, fostering the development of more efficient and accurate diagnostic methods for Lyme disease. It is firmly believed that our research will serve as a catalyst, inspiring interdisciplinary collaborations that accelerate progress at the convergence of medicine, computing, and technology, ultimately benefiting public health. [ABSTRACT FROM AUTHOR]

Borrelia burgdorferi sensu lato is a species complex of pleomorphic spirochetes, including species that cause Lyme disease (LD) in humans. In addition to classic spiral forms, these bacteria are capable of creating morphological forms referred to as round bodies and aggregates. The subject of discussion is their possible contribution to the persistence of infection or post-infection symptoms in LD. This study investigates the immunological properties of these forms by monitoring reactivity with early (n = 30) and late stage (n = 30) LD patient sera and evaluating the immune response induced by vaccination of mice. In patient sera, we found a quantitative difference in reactivity with individual morphotypes, when aggregates were recognized most intensively, but the difference was statistically significant in only half of the tested strains. In post-vaccination mouse sera, we observed a statistically significant higher reactivity with antigens p83 and p25 (OspC) in mice vaccinated with aggregates compared to mice vaccinated with spiral forms. The importance of the particulate nature of the antigen for the induction of a Th1-directed response has also been demonstrated. In any of morphological forms, the possibility of inducing antibodies cross-reacting with human nuclear and myositis specific/associated autoantigens was not confirmed by vaccination of mice. [ABSTRACT FROM AUTHOR]

The spondyloarthropathies are a group of conditions characterised by spinal joint pain and have related clinical, epidemiological and genetic-related features. Ankylosing spondylitis, reactive arthritis, the spinal form of psoriatic arthritis and Crohn's and colitis enteropathic arthritis are the major clinical entities of the spondyloarthropathies, and principally occur in HLA-B27 positive individuals. Ankylosing spondylitis is much more common in males than females. Patients are usually seronegative for rheumatoid factor, and extra-articular features including iridocyclitis, mucous membrane and skin lesions: aortitis, may occur in some patients. The reactive arthritis form classically occurs following an infection of the gastrointestinal or genitourinary tract. The Crohn's and colitis enteropathic arthritis forms often have an associated large joint asymmetrical arthritis. Also discussed are acute rheumatic fever and Lyme disease which are conditions where the individual develops arthritis after an infection. [ABSTRACT FROM AUTHOR]

Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as well as kidney transplant patients with cytomegalovirus (CMV) and polyomavirus (BKV) infections. Using an antibody-based assay, we quantified ~ 350 cell surface markers, cytokines, and chemokines involved in inflammation and immunity. Unique protein signatures were identified specific to the acute phase of infection irrespective of the pathogen type, with significant changes during convalescence. In addition, tumor necrosis factor receptor superfamily member 6 (TNR6), C–C Motif Chemokine Receptor 7 (CCR7), and C–C motif chemokine ligand-1 (CCL1) were increased in the acute and convalescent phases across all viral, bacterial, and protozoan compared to blood from healthy donors. Furthermore, despite the differences between pathogens, proteins were enriched in common biological pathways such as cell surface receptor signaling pathway and response to external stimulus. In conclusion, we demonstrated that irrespective of the pathogen type, there are common immunoregulatory and proinflammatory signals. [ABSTRACT FROM AUTHOR]

There is mounting evidence of increases in tick (Acari: Ixodidae) contacts in Finland during the past few decades, highlighted by increases in the incidence of Lyme borreliosis and tick-borne encephalitis (TBE). While nationwide field studies to map distributions of ticks are not feasible, crowdsourcing provides a comprehensive method with which to assess large-scale changes in tick contact areas. Here, we assess changes in tick contact areas in Finland between 1958 and 2021 using three different nationwide crowdsourced data sets. The data revealed vast increases in tick contact areas, with ticks estimated to be contacted locally approximately 400 km further north in western and approximately 100 km further north in eastern Finland in 2021 than 1958. Tick contact rates appeared to be highest along the coastline and on the shores of large lakes, possibly indicating higher tick abundance therein. In general, tick observations per inhabitant increased from 2015 to 2021. Tick contact areas have expanded in Finland over the past 60 years. It appears that taiga ticks (Ixodes persulcatus) are behind most of the northwards shifts in tick contact areas, with Ixodes ricinus contributing mostly to new contact areas in the south. While ticks are now present in most of Finland, there are still areas where tick abundance is low and/or establishment not possible, mainly in northern Finland. [ABSTRACT FROM AUTHOR]

This article presents the results of a quarter of a century of cooperation between the Scientific Center for Family Health and Human Reproduction Problems (Irkutsk, Russia) and the National Centers for Zoonotic Infections (Ulaanbaatar and Sükhbaatar, Mongolia), as well as the current ecological and epidemiological situation and perspectives of future collaborative research. The current situation in the natural foci of tick-borne infections in the transboundary Russian–Mongolian territories indicates the need to continue joint research and improve existing monitoring. Based on the results of field research, laboratory diagnostics of biomaterials, and data on the official incidence of tick-borne infections, the epidemiological situation in near-border foci in Russia and Mongolia started worsening. In the territories of the taiga and forest-steppe landscapes of Mongolia, the taiga tick, the main vector of tick-borne encephalitis (TBE) and ixodid tick-borne borreliosis (Lyme disease), occurs with varying frequency and abundance. The second in importance and width of distribution is the steppe tick, which annually reaches several hundred per surveillance count in April–May in the steppe habitats. Up to 81% of the studied ticks contain viral and bacterial pathogens and can transmit these pathogens of dangerous diseases to humans. Since 2005, TBE has been diagnosed in 393 patients, Lyme disease in 276, and North Asian tick typhus in 2003, and patients with mixed infection were also diagnosed. More than half of the tick-borne disease cases were registered in Selenge aimag bordering Russia, which is one of the most affected in Mongolia in terms of tick-borne infections. For 18 years, the mortality comprised 0.9% (23 fatal cases). According to the official data of Rospotrebnadzor in the Republic of Buryatia in the border Tunkinsky district, the incidence of TBE had increased from one case in 2020 to six in 2022, whereas Lyme disease increased from four to seven cases. The results presented here indicate the need for urgent actions to prevent a further increase in tick-borne diseases. [ABSTRACT FROM AUTHOR]

Heterogeneous aggregation of parasites between individual hosts is common and regarded as an important factor in understanding transmission dynamics of vector-borne diseases. Lyme disease is vectored by generalist tick species, yet we have a limited understanding of how individual heterogeneities within small mammal host populations affect the aggregation of ticks and likelihood of infection. Male hosts often have higher parasite and infection levels than females, but whether this is linked to sexual body size dimorphism remains uncertain. Here, we analysed how host species, sex, and body mass influenced Ixodes ricinus tick infestations and the infection prevalence of Borrelia burgdorferi sensu lato (s.l.) in three species of small mammals involved in the enzootic transmission cycle of Lyme disease in Norway from 2018 to 2022. Larval and nymphal ticks were found on 98% and 34% of all individual hosts, respectively. In bank voles and wood mice, both larval and nymphal tick infestation and infection probability increased with body mass, and it increased more with mass for males than for females. Tick infestation in the common shrew increased with body mass and was higher in males, while pathogen infection was higher in females. Sex-biases in infestation did not correspond with level of sexual body mass dimorphism across species. This study contributes to our understanding of how individual heterogeneity among small mammalian hosts influences I. ricinus tick aggregation and prevalence of B. burgdorferi s.l. at northern latitudes. [ABSTRACT FROM AUTHOR]

Hard-bodied ticks have become a major concern in temperate regions because they transmit a variety of pathogens of medical significance. Ticks and pathogens interact with hosts in a complex social-ecological system (SES) that influences human exposure to tick-borne diseases (TBD). We argue that addressing the urgent public health threat posed by TBD requires an understanding of the integrated processes in the forest ecosystem that influence tick density and infection prevalence, transmission among ticks, animal hosts, and ultimately disease prevalence in humans. We argue that collaborative modeling of the human-tick SES is required to understand the system dynamics as well as move science toward policy action. Recent studies in human health have shown the importance of stakeholder participation in understanding the factors that contribute to human exposure to zoonotic diseases. We discuss how collaborative modeling can be applied to understand the impacts of forest management practices on ticks and TBD. We discuss the potential of collaborative modeling for encouraging participation of diverse stakeholders in discussing the implications of managing forest ticks in the absence of large-scale control policy. [ABSTRACT FROM AUTHOR]

Lyme borreliosis (LB) is caused by the transmission of Borrelia burgdorferi s.l. from ticks to humans. Climate affects tick abundance, and climate change is projected to promote shifts in abundance in Europe, potentially increasing human exposure. We analyzed serum samples collected between the years 2014–2019 from German National Cohort (NAKO) participants at four study sites (Augsburg, Berlin, Hanover, Münster) for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies using an enzyme‐linked immunosorbent assay (ELISA) and line blot immunoassay as confirmatory test for positive and equivocal ELISA samples. We reported crude and weighted seropositivity proportions for local estimates. We used mixed model analysis to investigate associated factors, such as age, sex, migration background, or animal contacts. We determined the serostatus of 14,207 participants. The weighted seropositivity proportions were 3.4% (IgG) and 0.4% (IgM) in Augsburg, 4.1% (IgG) and 0.6% (IgM) in northern Berlin, 3.0% (IgG) and 0.9% (IgM) in Hanover, and 2.7% (IgG) and 0.6% (IgM) in Münster. We found higher odds for IgG seropositivity with advancing age (p < 0.001), among males compared to females (p < 0.001) and reduced odds among participants with migration background compared to those without (p = 0.001). We did not find evidence for an association between serostatus and depression, children within the household, or animal contact, respectively. We found low seropositivity proportions and indications of differences across the study locations, although between-group comparisons did not yield significant results. Comparisons to earlier research are subject to important limitations; however, our results indicate no major increases in seropositivity over time. Nevertheless, monitoring of seropositivity remains critical in light of potential climate-related Borrelia exposure. [ABSTRACT FROM AUTHOR]

In Lyme borreliosis, the skin constitutes a major interface for the host, the bacteria and the tick. Skin immunity is provided by specialized immune cells but also by the resident cells: the keratinocytes and the fibroblasts. Discoveries on the role of the microbiome in the modulation of skin inflammation and immunity have reinforced the potential importance of the skin in vector-borne diseases. In this study, we analyzed in vitro the interaction of human primary keratinocytes and fibroblasts with Borrelia burgdorferi sensu stricto N40 in presence or absence of bacterial commensal supernatants. We aimed to highlight the role of resident skin cells and skin microbiome on the inflammation induced by B. burgdorferi s.s.. The secretomes of Staphylococcus epidermidis, Corynebacterium striatum and Cutibacterium acnes showed an overall increase in the expression of IL-8, CXCL1, MCP-1 and SOD-2 by fibroblasts, and of IL-8, CXCL1, MCP-1 and hBD-2 in the undifferentiated keratinocytes. Commensal bacteria showed a repressive effect on the expression of IL-8, CXCL1 and MCP-1 by differentiated keratinocytes. Besides the inflammatory effect observed in the presence of Borrelia on all cell types, the cutaneous microbiome appears to promote a rapid innate response of resident skin cells during the onset of Borrelia infection. [ABSTRACT FROM AUTHOR]

Theory predicts that biodiversity changes due to climate warming can mediate the rate of disease emergence. The mechanisms linking biodiversity-disease relationships have been described both theoretically and empirically but remain poorly understood. We investigated the relations between host diversity and abundance and Lyme disease risk in southern Quebec, a region where Lyme disease is rapidly emerging. We found that both the abundance of small mammal hosts and the relative abundance of the tick's natural host, the white-footed mouse (Peromyscus leucopus), influenced measures of disease risk in tick vectors (Borrelia burgdorferi infection abundance and prevalence in tick vectors). Our results suggest that the increase in Lyme disease risk is modulated by regional processes involving the abundance and composition of small mammal assemblages. However, the nature and strength of these relationships was dependent both on time and geographic area. The strong effect of P. leucopus abundance on disease risk we report here is of significant concern, as this competent host is predicted to increase in abundance and occurrence in the region, with the northern shift in the range of North American species under climate warming. [ABSTRACT FROM AUTHOR]

The spirochete bacterial pathogen Borrelia (Borreliella) burgdorferi (Bbu) affects more than 10% of the world population and causes Lyme disease in about half a million people in the US annually. Therapy for Lyme disease includes antibiotics that target the Bbu ribosome. Here we present the structure of the Bbu 70S ribosome obtained by single particle cryo-electron microscopy at 2.9 Å resolution, revealing a bound hibernation promotion factor protein and two genetically non-annotated ribosomal proteins bS22 and bL38. The ribosomal protein uL30 in Bbu has an N-terminal α-helical extension, partly resembling the mycobacterial bL37 protein, suggesting evolution of bL37 and a shorter uL30 from a longer uL30 protein. Its analogy to proteins uL30m and mL63 in mammalian mitochondrial ribosomes also suggests a plausible evolutionary pathway for expansion of protein content in mammalian mitochondrial ribosomes. Computational binding free energy predictions for antibiotics reflect subtle distinctions in antibiotic-binding sites in the Bbu ribosome. Discovery of these features in the Bbu ribosome may enable better ribosome-targeted antibiotic design for Lyme disease treatment. Ribosomes are prime targets for antibiotics in pathogenic bacteria. Here, cryo-electron microscopy reveals features in the Borrelia burgdorferi ribosome that provide insights into ribosome evolution, dormancy, and antibiotic binding. [ABSTRACT FROM AUTHOR]

Recent philosophical literature has highlighted the complexities of handling dissent in science. On one hand, scientific dissent can be very harmful, as when “merchants of doubt” strategically appeal to dissent in order to undermine important environmental and public-health initiatives. On the other hand, scientific dissent can also be beneficial when it helps to promote scientific objectivity, progress, and public engagement. Some authors have responded to this tension by suggesting criteria for distinguishing normatively appropriate and inappropriate dissent, while other authors have suggested that it is more fruitful to alter the social context in which science operates in order to alleviate the negative effects of dissent over the long term. This paper proposes another approach that may be helpful for managing particularly challenging cases of scientific dissent. It argues that instances of scientific dissent often incorporate debates over value judgments, so many difficult cases of dissent can be navigated by: (1) identifying and highlighting those value judgments; and (2) managing those value judgments by drawing strategies from the extensive literature on values and science. The paper illustrates this approach by examining a case study of dissent over the treatment of long-term symptoms associated with Lyme disease. [ABSTRACT FROM AUTHOR]

2a, 3a, c, d and 6e. The HTML has been updated to include a corrected version of the Supplementary Information; the original incorrect versions of these Supplementary Figures can be found as Supplementary Information associated with this Correction. The HTML has been updated to include corrected versions of both files; the original incorrect versions of Supplementary Data 2 and Source Data can be found as Supplementary Information associated with this Correction. The original version of the Supplementary Information associated with this Article included an incorrect Supplementary Data 2 file and an incorrect Source Data file. [Extracted from the article]

Tropical theileriosis, babesiosis, and anaplasmosis are the most dominant tick-borne infections in North Africa where they cause significant economic losses in ruminants' industry. The aim of the present work was to study infections and co-infection patterns in 66 cattle with clinical signs of piroplasmosis and/or anaplasmosis in two localities, Beni Hamidene and Grarem Gouga, districts of Constantine and Mila (Northeast of Algeria), respectively. This study was conducted between early May and late September during four years 2017, 2018, 2020, and 2021. PCR showed that the most frequent pathogen in cattle with clinical signs of piroplasmosis and/or anaplasmosis was Theileria annulata (66/66; 100%) followed by Babesia bovis (21/66; 31.8%), Anaplasma marginale (15/66; 22.7%), and Babesia bigemina (3/66; 4.5%) (p < 0.001). Giemsa-stained blood smears examinations revealed that 66.7% (44/66); 10.6% (7/66); and 9.1% (6/66) of cattle were infected by T. annulata, Babesia spp., and A. marginale, respectively (p < 0.001). PCR revealed seven co-infection patterns: T. annulata/A. marginale (15/66; 22.7%), T. annulata/B. bovis (21/66; 31.8%), T. annulata/B. bigemina (3/66; 4.5%), T. annulata/A. marginale/B. bovis (7/66; 10.6%), T. annulata/B. bovis/B. bigemina (2/66; 3%), T. annulata/A. marginale/B. bigemina (1/66; 1.5%), and T. annulata/A. marginale/B. bigemina/B. bovis (1/66; 1.5%). Phylogenetic analyses showed that T. annulata Tams1 and B. bigemina gp45 sequences were identical to isolates from Mauritania and South Africa, respectively. The three A. marginale amplicons obtained herein had 99.63 to 99.88% similarity between them. This study provides data that can be used to improve control programs targeting these cattle hemopathogens. [ABSTRACT FROM AUTHOR]

Aim: The COVID-19 pandemic resulted in a wide range of serious health, social and economic consequences. To counteract the pandemic, various measures and restrictions such as lockdowns, closures, social distancing, hygiene, and protective measures such as wearing face masks have been enforced. Apart from the COVID-19 pandemic, these measures also had effects on other transmittable diseases. This study therefore determined the impact on case numbers and interest for other infectious diseases as well. Subject and methods: Anonymized data on reported case numbers from the German Robert Koch Institute and data from Google Trends about the search interest have been used in this study to track courses of infectious diseases before and during the coronavirus pandemic in Germany. Results: The results of this analysis clearly demonstrated that the case numbers of influenza, whooping cough, measles, mumps, scarlet fever and chicken pox decreased in the pandemic years, most probably due to anti-pandemic measures in Germany. Additionally, the Google Trends analysis demonstrated public awareness, documented by a corresponding search interest, for the new topic COVID-19 and for other infectious diseases. Conclusion: Online available data provided valuable sources for research purposes in infodemiology or infoveillance. Highlights: COVID-19 dominated public search interest for infectious diseases during the pandemic. Reduction in case numbers of influenza, whooping cough, measles, mumps, scarlet fever and chicken pox was shown for pandemic years. Google Trends was shown as a functional tool, well suited for demonstrating the population's awareness of certain infectious diseases. [ABSTRACT FROM AUTHOR]

In Poland, tick-borne diseases constitute the majority of diseases related to exposure to biological agents with a predominance of Lyme borreliosis; therefore, research on ticks as a reservoir of various pathogens remains crucial in the epidemiology of human diseases after tick bites. This study aimed to identify the occurrence of Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Neoehrlichia mikurensis, and Babesia spp. in ticks collected from vegetation in eastern Poland. Additionally, the prevalence of co-infections in the adult Ixodes ricinus ticks was determined. Among I. ricinus ticks the predominantly detected pathogen was B. burgdorferi s.l. (23%) with B. burgdorferi sensu stricto as the most frequently identified species, followed by B. garinii. In 2013, the double or triple infections of B. burgdorferi s.s., B. afzelii, and B. garinii species did not exceed 9% in adult ticks, whereas in 2016, the prevalence of mixed infections reached 29%. The prevalence of N. mikurensis and B. miyamotoi in I. ricinus was determined at the same level of 2.8%. Four Babesia species were identified in the examined I. ricinus population: B. microti (1.5%), B. venatorum (1.2%), B. divergens (0.2%), and B. capreoli (0.1%). Co-infections were detected in 10.1% of all infected ticks with the highest prevalence of co-infections with B. burgdorferi s.l. and Babesia species. The changes in the prevalence and the distribution of particular pathogens within tick populations indicate the need for monitoring the current situation related to tick-borne pathogens from the aspect of risk to human health. [ABSTRACT FROM AUTHOR]

The hard tick, Ixodes ricinus, a main Lyme disease vector, harbors an intracellular bacterial endosymbiont. Midichloria mitochondrii is maternally inherited and resides in the mitochondria of I. ricinus oocytes, but the consequences of this endosymbiosis are not well understood. Here, we provide 3D images of wild-type and aposymbiotic I. ricinus oocytes generated with focused ion beam-scanning electron microscopy. Quantitative image analyses of endosymbionts and oocyte mitochondria at different maturation stages show that the populations of both mitochondrion-associated bacteria and bacterium-hosting mitochondria increase upon vitellogenisation, and that mitochondria can host multiple bacteria in later stages. Three-dimensional reconstructions show symbiosis-dependent morphologies of mitochondria and demonstrate complete M. mitochondrii inclusion inside a mitochondrion. Cytoplasmic endosymbiont located close to mitochondria are not oriented towards the mitochondria, suggesting that bacterial recolonization is unlikely. We further demonstrate individual globular-shaped mitochondria in the wild type oocytes, while aposymbiotic oocytes only contain a mitochondrial network. In summary, our study suggests that M. mitochondrii modulates mitochondrial fragmentation in oogenesis possibly affecting organelle function and ensuring its presence over generations. The mitochondrial symbiont, Candidatus Midichloria mitochondrii, exists in the hard tick Ixodus ricinus, the main vector for Lyme disease. Here, the authors use FIB-SEM to characterise mitochondrial morphology and bacterial interactions in the context of oocyte maturation and endosymbiosis. [ABSTRACT FROM AUTHOR]

Transcription termination is an essential and dynamic process that can tune gene expression in response to diverse molecular signals. Yet, the genomic positions, molecular mechanisms, and regulatory consequences of termination have only been studied thoroughly in model bacteria. Here, we use several RNA-seq approaches to map RNA ends for the transcriptome of the spirochete Borrelia burgdorferi – the etiological agent of Lyme disease. We identify complex gene arrangements and operons, untranslated regions and small RNAs. We predict intrinsic terminators and experimentally test examples of Rho-dependent transcription termination. Remarkably, 63% of RNA 3′ ends map upstream of or internal to open reading frames (ORFs), including genes involved in the unique infectious cycle of B. burgdorferi. We suggest these RNAs result from premature termination, processing and regulatory events such as cis-acting regulation. Furthermore, the polyamine spermidine globally influences the generation of truncated mRNAs. Collectively, our findings provide insights into transcription termination and uncover an abundance of potential RNA regulators in B. burgdorferi. Transcription termination can tune bacterial gene expression in response to diverse signals. Here, the authors use several RNA-seq approaches to map RNA ends for the transcriptome of the spirochete Borrelia burgdorferi, providing insights into various modes of transcription termination and identifying potential RNA regulators in this pathogen. [ABSTRACT FROM AUTHOR]

There are no assays for detecting B. burgdorferi antigen in blood of infected Lyme disease individuals. Here, we provide proof-of-principle evidence that we can quantify B. burgdorferi antigen in spiked blood using a portable smartphone-based fluorescence microscope that measures immunoagglutination on a paper microfluidic chip. We targeted B. burgdorferi OspA to develop a working prototype and added examples of two antigens (OspC and VlsE) that have diagnostic value for discrimination of Lyme disease stage. Using an extensively validated monoclonal antibody to OspA (LA-2), detection of OspA antigen had a broad linear range up to 100 pg/mL in 1% blood and the limit of detection (LOD) was 100 fg/mL (= 10 pg/mL in undiluted blood), which was 1000 times lower than our target of 10 ng/mL. Analysis of the two other targets was done using polyclonal and monoclonal antibodies. OspC antigen was detected at LOD 100 pg/mL (= 10 ng/mL of undiluted blood) and VlsE antigen was detected at LOD 1–10 pg/mL (= 0.1–1 ng/mL of undiluted blood). The method is accurate and was performed in 20 min from sample to answer. When optimized for detecting several B. burgdorferi antigens, this assay may differentiate active from past infections and facilitate diagnosis of Lyme disease in the initial weeks of infection, when antibody presence is typically below the threshold to be detected by serologic methods. [ABSTRACT FROM AUTHOR]

Lyme neuroborreliosis (LNB) is a manifestation of Lyme disease involving the central and peripheral nervous system. It is caused by the spirochete Borrelia burgdorferi, transmitted by tick bites to a human host. Clinical signs of LNB develop after the dissemination of the pathogen to the nervous system. The infection occurs in children and adults, but the clinical manifestations differ. In adults, painful meningoradicultis is the most common manifestation of LNB, while children often present with facial nerve palsy and/or subacute meningitis. Subacute headache can be the only manifestation of LNB in children, especially during the summer months in Lyme disease-endemic regions. Non-specific symptoms, such as loss of appetite, fatigue or mood changes, may also occur, especially in young children. A high level of suspicion and early recognition of the various clinical manifestations presented by children with LNB is essential to minimize delay in diagnosis and optimize management. This review provides an overview of the spectrum of clinical manifestations, and discusses diagnosis, antibiotic treatment, and clinical outcome of LNB in children. [ABSTRACT FROM AUTHOR]

Background: Complete recovery after adequately treated neuroborreliosis is common, but studies report that some patients experience persistent symptoms like self-reported cognitive problems and fatigue. Persisting symptoms are often termed post-Lyme disease syndrome, of which etiology is not clearly understood. The aim of this study was to investigate cognitive function, possible structural changes in brain regions and level of fatigue. We have not found previous studies on neuroborreliosis that use standardized neuropsychological tests and MRI with advanced image processing to investigate if there are subtle regional changes in cortical thickness and brain volumes after treatment. Methods: We examined 68 patients treated for neuroborreliosis 6 months earlier and 66 healthy controls, with a comprehensive neuropsychological test protocol, quantitative structural MRI analysis of the brain and Fatigue Severity Scale. Results: We found no differences between the groups in either cognitive function, cortical thickness or brain volumes. The patients had higher score on Fatigue Severity Scale 3.8 vs. 2.9 (p = 0.001), and more patients (25.4%) than controls (5%) had severe fatigue (p = 0.002), but neither mean score nor proportion of patients with severe fatigue differed from findings in the general Norwegian population. Conclusion: The prognosis regarding cognitive function, brain MRI findings and fatigue after adequately treated neuroborreliosis is favorable. [ABSTRACT FROM AUTHOR]

Lyme neuroborreliosis (LNB) is a tick-borne infection caused by Borrelia burgdorferi which can affect the nervous system in adults and children. The clinical course of LNB in adults is often different than in children. Studies comparing these differences are scarce. The aim of this study was to compare the clinical characteristics and outcome of LNB between children and adults. We performed an observational retrospective study among patients with LNB who presented at Gelre Hospital from 2007 to 2020 and had cerebrospinal fluid pleocytosis. Data were collected from electronic medical records. A total of 127 patients with LNB were identified. Included were 58 children (median age 8 years) and 69 adults (median age 56 years). The incidence of LNB was 3.2 per 100,000 inhabitants per year. The most common neurological manifestation in adults and in children was facial nerve palsy (67%). Unilateral facial nerve palsy was more prevalent in children (85%) than in adults (42%) (P < 0.001). Headache was also more prevalent in children (59%) than in adults (32%) (P = 0.003). (Poly)radiculitis was more prevalent in adults (51%) than in children (3%) (P < 0.001), encephalitis was not reported in children. In children, the time between symptom onset and diagnosis was 10 days versus 28 days in adults (P < 0.001). Complete recovery was reported significantly more often in children (83%) compared to adults (40%) (P < 0.001). Conclusion: In a Lyme-endemic area in the Netherlands, LNB commonly presents with facial nerve palsy. Facial nerve palsy and headache are more prevalent in children, while radiculitis and encephalitis are mostly reported in adults. What is Known: • The clinical course of Lyme neuroborreliosis in adults is often different from children.. • The aim of this study was to compare the clinical characteristics and outcome of LNB between children and adults. What is New: • Lyme neuroborreliosis in the Netherlands commonly presents with facial nerve palsy. • Facial nerve palsy and headache are more prevalent in children than in adults. Radiculitis and encephalitis are mostly reported in adults. [ABSTRACT FROM AUTHOR]

Lyme borreliosis (LB) and West Nile fever (WNF) are among the most common vector-borne human infections. Both infections involve birds in their enzootic transmission cycle. Currently, there is no available data on possible circulation of Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) and West Nile virus (WNV) in wild birds in Bulgaria. Serum samples from 160 wild birds of 18 species collected in May and in September 2021 in two regions of Bulgaria were tested by ELISA for antibodies to B. burgdorferi s.l. and WNV. Specific antibodies were found in 56 (35.0%) of all tested birds. Antibodies to B. burgdorferi s.l. were present in 40 (25.0%) and antibodies to WNV were found in 28 (17.5%) of the birds. Simultaneous presence of antibodies against both pathogens was detected in 12 (7.5%) of the tested birds. Analysis of the results by bird species showed that out of the 18 different bird species, antibodies against at least one of the two tested infectious agents were found in nine: Acrocephalus arundinaceus (Linnaeus, 1758), Cyanistes caeruleus (Linnaeus, 1758), Fringilla coelebs (Linnaeus, 1758), Garrulus glandarius (Linnaeus, 1758), Luscinia megarhynchos (Brehm, 1831), Parus major (Linnaeus, 1758), Passer domesticus (Linnaeus, 1758), Sitta europaea (Linnaeus, 1758) and Turdus merula (Linnaeus, 1758). This study observed high levels of antibodies against the etiological agents of Lyme borreliosis and WNF in wild resident and migratory birds. The highest seropositivity levels against both pathogens were found in three species – P. major, T. merula and L. megarhynchos. The results confirmed active circulation of B. burgdorferi s.l. and WNV in the bird population and defined its importance as a reservoir. [ABSTRACT FROM AUTHOR]

Understanding the ecology of the often dense white-tailed deer populations in urban and suburban landscapes is important for mitigating a variety of conflicts that arise with dense human populations, such as issues surrounding zoonotic disease mitigation. We collared white-tailed deer in highly suburban areas of Howard County, Maryland with high-resolution GPS collars. Then, we created autocorrelated kernel density home ranges for broader land use analyses and concurrently used general additive models to characterize fine-scale hourly measures of speed, activity, and proximity to residential buildings. Suburban deer home ranges encompassed approximately 35% direct residential land, and an average of 71 and 129 residential properties were found within female and male core ranges, respectively. Sex, time of day, and day of year all influenced fine-scale speeds, activity levels, and proximity to residential property buildings. Deer moved into residential areas nightly, especially in winter, and exhibited bouts of increased speed and activity shortly after sunrise and sunset, with distinctive seasonal changes. We discuss how variation in home ranges and movements may influence population management success and explore year-round periods of increased risk of deer transporting ticks to residential areas. These findings focus our broad understanding of deer movements in suburban and urban landscapes to improve deer population management and to mitigate the spread of ticks into residential areas. [ABSTRACT FROM AUTHOR]

Ixodes ricinus ticks (Acari: Ixodidae) are the most important vector for Lyme borreliosis in Europe. As climate change might affect their distributions and activities, this study aimed to determine the effects of environmental factors, i.e., meteorological, bioclimatic, and habitat characteristics on host-seeking (questing) activity of I. ricinus nymphs, an important stage in disease transmissions, across diverse climatic types in France over 8 years. Questing activity was observed using a repeated removal sampling with a cloth-dragging technique in 11 sampling sites from 7 tick observatories from 2014 to 2021 at approximately 1-month intervals, involving 631 sampling campaigns. Three phenological patterns were observed, potentially following a climatic gradient. The mixed-effects negative binomial regression revealed that observed nymph counts were driven by different interval-average meteorological variables, including 1-month moving average temperature, previous 3-to-6-month moving average temperature, and 6-month moving average minimum relative humidity. The interaction effects indicated that the phenology in colder climates peaked differently from that of warmer climates. Also, land cover characteristics that support the highest baseline abundance were moderate forest fragmentation with transition borders with agricultural areas. Finally, our model could potentially be used to predict seasonal human-tick exposure risks in France that could contribute to mitigating Lyme borreliosis risk. [ABSTRACT FROM AUTHOR]

Objectives: Age-related physiological changes, particularly immune system decline, may contribute to greater vulnerability to infectious diseases in older individuals. A growing body of evidence shows that both, acute, and chronic infections may be accompanied by cognitive disturbances as part of their manifestations. Given the importance of cognition in aging trajectories, the objective of this article was to review current knowledge on cognitive outcomes of infectious diseases in older adults, and to emphasize the importance of considering cognition as a domain of interest in its own rights in these diseases. Methods: A MEDLINE/PubMed database search was conducted to identify articles reporting cognitive impairment associated with various severe acute infections and specific chronic infectious conditions such as human immune deficiency virus, the herpes virus family, hepatitis C virus, Lyme borreliosis, Helicobacter pylori, periodontitis, and emerging pathogens like SARS-CoV-2, as well as potentially preventive strategies like vaccination. Results/ Conclusions: Taken together, the studies examined in the present review emphasize that numerous acute and chronic infectious diseases share mechanisms that, when added to specific risk factors frequently found in older persons, contribute to considerably increase the risk of cognitive outcomes such as cognitive decline and dementia. This review may help to appreciate the role that infectious diseases play in cognitive trajectories and thus promote further investigation on the topic. [ABSTRACT FROM AUTHOR]

Two different stroke mechanisms are involved in small vessel disease: branch atheromatous disease (BAD) and lipohyalinotic degeneration (LD). We compared mechanisms of stroke in lenticulostriate arteries (LSA) vs. anterior pontine arteries (APA) and verified factors associated with stroke mechanisms, including shape of middle cerebral artery (MCA) and basilar artery (BA). We retrospectively reviewed patients with acute ischemic stroke with penetrating artery territory confirmed by MRI. The mechanisms of stroke were categorized based on diffusion-weighted imaging; BAD was defined as lesion larger than 10 mm in LSA and lesions involving basal pontine in APA. Other lesions were classified as LD. The shapes of MCA and BA were classified as straight, with one angle, or with two angles (U, C or S shape, respectively) using anterior–posterior view. The study included 221 patients. LD was more common in LSA infarcts, but BAD was more common in APA infarcts (p < 0.001). Low initial National Institutes of Health Stroke Scale [Adjusted Odds ratio (aOR) = 0.78; p < 0.001], absence of hyperlipidemia [aOR = 0.31; p = 0.002], previous statin use [aOR = 4.35; p = 0.028] LSA infarcts [reference = APA territory; aOR = 11.07; p < 0.001], and S-shaped vessels (reference = straight shaped vessels; aOR = 3.51; p = 0.004) were independently associated with LD. Angulations in the mother vessels may be more associated with true small vessel disease more with LD than BAD. [ABSTRACT FROM AUTHOR]

Predictors for the risk of severe COVID-19 are crucial for patient care and control of the disease. Other infectious diseases as potential comorbidities in SARS-CoV-2 infection are still poorly understood. Here we identify association between the course of COVID-19 and Lyme disease (borreliosis), caused by Borrelia burgdorferi transmitted to humans by ticks. Exposure to Borrelia was identified by multi-antigenic (19 antigens) serological testing of patients: severe COVID-19 (hospitalized), asymptomatic to mild COVID-19 (home treated or not aware of being infected), and not infected with SARS-CoV-2. Increased levels of Borrelia-specific IgGs strongly correlated with COVID-19 severity and risk of hospitalization. This suggests that a history of tick bites and related infections may contribute to the risks in COVID-19. Though mechanisms of this link is not clear yet, screening for antibodies targeting Borrelia may help accurately assess the odds of hospitalization for SARS-CoV-2 infected patients, supporting efforts for efficient control of COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Little is known on coping strategies in patients with chronic symptoms suspected of Lyme borreliosis (LB). Different coping strategies might influence quality of life (QoL). We assessed coping strategies and QoL in patients with chronic symptoms suspected of LB. Methods: Adult patients referred to the Lyme Center Apeldoorn were included (November 2019–April 2021). Participants completed the RAND-36 to assess QoL and the Utrecht Coping List to assess coping strategies. Patient data were extracted from medical records. Patients were categorized based on clinical LB and serology. Linear regression analyses were conducted to examine an association between coping strategies and QoL subscales. Results: Included were 201 patients. Patients suspected of LB had a different coping profile and lower QoL compared to the reference population. Patients with negative serology and no clinical LB scored lowest on all QoL subscales. In multivariate analyses, correcting for age, gender, comorbidity, and patient category, a negative association was found between passive coping and the QoL subscales physical functioning (β(SE) = − 1.1(0.5)), social functioning (β(SE) = − 3.3(0.5)), role limitations (emotional) (β(SE) = − 5.5(0.8)), mental health (β(SE) = − 3.7(0.3)), vitality (β(SE) = − 2.3(0.3)), pain (β(SE) = − 2.3(0.5)), and general health (β(SE) = − 2.7(0.3)). A negative association was also found between palliative coping and the QoL subscale role limitations (physical) (β(SE) = − 1.8(0.6)) and between expressing emotions and mental health (β(SE) = − 1.3(0.6)). A positive association was found between active coping and the QoL subscales mental health (β(SE) = 1.0(0.3)) and role limitations (emotional) (β(SE) = 1.9(0.8)). Conclusion: In patients suspected of LB, dysfunctional coping strategies were associated with worse quality of life. There is a need for interventions that can guide patients with chronic symptoms suspected of LB towards more active coping and increase QoL. [ABSTRACT FROM AUTHOR]

Climate change is adversely affecting the burden of infectious disease throughout the world, which is a health security threat. Climate-sensitive infectious disease includes vector-borne diseases such as malaria, whose transmission potential is expected to increase because of enhanced climatic suitability for the mosquito vector in Asia, sub-Saharan Africa, and South America. Climatic suitability for the mosquitoes that can carry dengue, Zika, and chikungunya is also likely to increase, facilitating further increases in the geographic range and longer transmission seasons, and raising concern for expansion of these diseases into temperate zones, particularly under higher greenhouse gas emission scenarios. Early spring temperatures in 2018 seem to have contributed to the early onset and extensive West Nile virus outbreak in Europe, a pathogen expected to expand further beyond its current distribution, due to a warming climate. As for tick-borne diseases, climate change is projected to continue to contribute to the spread of Lyme disease and tick-borne encephalitis, particularly in North America and Europe. Schistosomiasis is a water-borne disease and public health concern in Africa, Latin America, the Middle East, and Southeast Asia; climate change is anticipated to change its distribution, with both expansions and contractions expected. Other water-borne diseases that cause diarrheal diseases have declined significantly over the last decades owing to socioeconomic development and public health measures but changes in climate can reverse some of these positive developments. Weather and climate events, population movement, land use changes, urbanization, global trade, and other drivers can catalyze a succession of secondary events that can lead to a range of health impacts, including infectious disease outbreaks. These cascading risk pathways of causally connected events can result in large-scale outbreaks and affect society at large. We review climatic and other cascading drivers of infectious disease with projections under different climate change scenarios. 5E6fdnCC7GZ6vtJap2g1wp Supplementary file1 (MP4 328467 KB) [ABSTRACT FROM AUTHOR]

The blacklegged tick, Ixodes scapularis, vectors Borrelia burgdorferi, a bacterium that causes Lyme Disease. Although synthetic pesticides can reduce tick numbers, there are concerns about their potential effects on beneficial insects, such as pollinators. Plant-based pest control agents such as essential oils could provide an alternative because they have low environmental persistency; however, these products struggle to provide effective control. We found a new natural acaricide, balsam fir (Abies balsamea) needles, that kill overwintering I. scapularis ticks. We extracted the essential oil from the needles, analyzed its chemical composition, and tested it for acaricidal activity. We placed ticks in tubes with substrate and positioned the tubes either in the field or in incubators simulating winter temperatures. We added balsam fir essential oil, or one of the main components of balsam fir essential oil (i.e., ß-pinene), to each tube. We found that both the oil and ß-pinene kill overwintering ticks. Whole balsam fir needles require several weeks to kill overwintering ticks, while the essential oil is lethal within days at low temperatures (≤ 4 °C). Further, low temperatures increased the efficacy of this volatile essential oil. Higher temperatures (i.e., 20 °C) reduce the acaricidal effectiveness of the essential oil by 50% at 0.1% v/v. Low temperatures may promote the effectiveness of other natural control products. Winter is an overlooked season for tick control and should be explored as a possible time for the application of low toxicity products for successful tick management. [ABSTRACT FROM AUTHOR]

Lyme borreliosis (LB) is the most common tick-borne infection in Europe, with Lyme neuroborreliosis (LNB) its second most frequent clinical manifestation. Prognostic factors for clinical outcomes in LNB have not been identified. Elevated serum levels of the brain damage markers neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have been associated with poor clinical outcomes in other disorders of the central nervous system. The aim of this study is to assess NSE and S100B in serum as prognostic biomarkers for clinical outcomes in paediatric LNB patients. Children evaluated for LNB (n = 121) in Sweden were prospectively included during 2010–2014, serum samples were collected on admission, and all children underwent a 2-month follow-up. Patients with pleocytosis and anti-Borrelia antibodies in cerebrospinal fluid (CSF) were classified as having LNB (n = 61). Controls were age- and gender-matched non-LNB patients (n = 60). NSE was elevated in 38/61 (62%) LNB patients and in 31/60 (52%) controls. S100B was elevated in 3/60 (5%) LNB patients and 0/59 (0%) controls. NSE and S100B concentrations did not differ significantly when comparing LNB patients with controls. No differences were found in the concentrations when comparing the clinical recovery of LNB patients at the 2-month follow-up. NSE was detectable in the majority of LNB patients and controls, whereas S100B was detectable in only a few LNB patients and no controls. NSE and S100B in serum cannot be recommended as prognostic biomarkers for clinical outcomes in children with LNB. [ABSTRACT FROM AUTHOR]