Diagnosis and management of suspected Lyme neuroborreliosis-related facial nerve palsy in children by paediatricians and general practitioners: a French survey.

The diagnosis and management of facial nerve palsy in children in Lyme borreliosis endemic area can be complex. The objective of this study was to evaluate the diagnosis and management of children with suspected Lyme neuroborreliosis (LNB)-related facial nerve palsy by general practitioners (GP) and paediatricians. We conducted a prospective national survey of clinical practice between September 2018 and January 2020. The questionnaire was intended for GPs and paediatricians. It is based on two distinct clinical situations (a 10-year-old child and a 5-year-old child) and contains questions about the diagnosis and management of facial nerve palsy in children with a recent tick bite. We obtained 598 responses (350/4125 paediatricians and 245/577 GPs). For a 10-year-old child with a facial nerve palsy in the context of a tick bite, more than half of GPs (52%) required a paediatric infectious consultation and 18% an admission to the hospital for lumbar puncture before the result of Lyme serology. The most prescribed antimicrobial therapies were amoxicillin (32%) and ceftriaxone (29%). For a 5-year-old child, there is no difference in the diagnosis of LNB and treatment except for doxycycline which was less prescribed. Concerning treatment, 18% of practitioners prescribed antibiotic therapy only (14% of GPs vs 21% of paediatricians, p = 0.09), and 17% prescribed antibiotic therapy combined with corticosteroids (14% of GPs vs 19% of paediatricians, p = 0.15). Finally, 93% of GPs and 75% of paediatricians reported to be uncomfortable with the diagnosis of LNB in children. CONCLUSION: Most participants were uncomfortable with the diagnosis of LNB. There was a limited difference in the management of LNB in children between GPs and paediatricians. WHAT IS KNOWN: • Lyme neuroborreliosis (LNB) is the second cause of facial nerve palsy in Europe, and its diagnosis is based on neurological symptoms and a lumbar puncture. However, no clinical criteria could be used to differentiate Bell's palsy and LNB. Moreover, data on the adjunctive corticosteroid treatment and outcome in patients with LNB-related facial nerve palsy are controversial. WHAT IS NEW: • Most participants were uncomfortable with the diagnosis of LNB. Its management was heterogeneous and most often not consistent with guidelines. Only 28% of participants requested a lumbar puncture in cases of suspected LNB, and 17% prescribed antibiotics with corticosteroids. • This study highlights the need for new specific guidelines in management (need for lumbar puncture and/or LB serology) and treatment (time to antibiotic initiation, probabilistic therapy, role of corticosteroids, doxycycline in children younger than 8 years) of LNB in children.

Case Report: A Typical Lyme Disease With Uncommon Neurologic Presentation.

Lyme disease is a very common infectious disease worldwide. The seventh cranial nerve palsy occurred in 9% of Lyme disease cases and the majority of them present as unilateral facial palsy. We present a rare case of bilateral facial palsy in Lyme disease due to Borrelia burgdorferi infection. A total of eleven cases of Lyme disease with bilateral facial palsy reported in literature were summarized and compared to our case. The diagnosis and management of Lyme disease with facial nerve palsy were also discussed in this article.

Complement therapeutic Factor H-IgG proteins as pre-exposure prophylaxes against Lyme borreliae infections.

Lyme disease (LD) is the most common vector-borne disease in the northern hemisphere and is caused by the bacteria Borrelia burgdorferi sensu lato (also known as Lyme borreliae) with no effective prevention available. Lyme borreliae evade complement killing, a critical arm of host immune defense, by producing outer surface proteins that bind to a host complement inhibitor, factor H (FH). These outer surface proteins include CspA and CspZ, which bind to the 6th and 7th short consensus repeats of FH (SCR(6-7)), and the OspE family of proteins (OspE), which bind to the 19th and 20th SCR (SCR19-20). In this study, we produced two chimeric proteins, FH-Fc, containing the Fc region of immunoglobulin G (Fc) with SCR(6-7) or SCR(19-20). We found that both FH-Fc constructs killed B. burgdorferi in the presence of complement and reduced bacterial colonization and LD-associated joint inflammation in vivo. While SCR(6-7)-Fc displayed Lyme borreliae species-specific bacterial killing, SCR(19-20)-Fc versatilely eradicated all tested bacterial species/strains. This correlated with SCR(6-7)-Fc binding to select variants of CspA and CspZ, but SCR(19-20)-Fc binding to all tested OspE variants. Overall, we demonstrated the concept of using FH-Fc constructs to kill Lyme borreliae and defined underlying mechanisms, highlighting the potential of FH-Fc as a pre-exposure prophylaxis against LD infection.

Pregnancy Among Reported Lyme Disease Cases-United States, 1992-2019.

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

Current and emerging approaches for eliminating Borrelia burgdorferi and alleviating persistent Lyme disease symptoms.

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

Age- and Sex-Specific Differences in Lyme Disease Health-Related Behaviors, Ontario, Canada, 2015-2022.

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

Rapid Increase in Seroprevalence of Borrelia burgdorferi Antibodies among Dogs, Northwestern North Carolina, USA, 2017-20211.

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

Dependence of Lyme disease incidence in children on environmental factors in Wielkopolska Province (West-Central Poland).

Introduction and Objective. Lyme borreliosis (LB) causes hundreds of thousands of new human infections worldwide annually. This is the first study connecting the LB risk to children with environmental factors. Materials and Method. The potential impacts were assessed of environmental factors (deer density in forests, coverage of potential broadleaved forest plant communities, urbanization index) on the number of LB cases in children. Analysis covered the medical records of 196 children diagnosed with LB (ICD- A69.2) from 1 January 2012 - 30 October 2021 in Wielkopolska Province (Poland). Results. All examined factors were positively correlated with LB cases. The highest correlation with the number of patients diagnosed with LB was presented by the degree of urbanization (percentage of the population living in cities in the total inhabitants of the study region). The number of cases was much higher in the second research period (2017-2021). Conclusions. The number of LB cases in children is increasing as the coverage of potential broadleaved forest plant communities increases. The number of cases among males is positively correlated with the coverage. Deer density is positively correlated with the number of LB cases among children - the higher the deer density, the greater the risk of LB infection. LB cases in children are positively correlated with the urbanization index - the more people that live in cities, the greater the risk to children of LB infection.

New BB0108, BB0126, BB0298, BB0323, and BB0689 Chromosomally Encoded Recombinant Proteins of Borrelia burgdorferi sensu lato for Serodiagnosis of Lyme Disease.

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

Novel recombinant vaccinia virus-vectored vaccine affords complete protection against homologous Borrelia burgdorferi infection in mice.

The rising prevalence of Lyme disease (LD) in North America and Europe has emerged as a pressing public health concern. Despite the availability of veterinary LD vaccines, no vaccine is currently available for human use. Outer surface protein C (OspC) found on the outer membrane of the causative agent, Borrelia burgdorferi, has been identified as a promising target for LD vaccine development due to its sustained expression during mammalian infection. However, the efficacy and immunological mechanisms of LD vaccines solely targeting OspC are not well characterized. In this study, we developed an attenuated Vaccinia virus (VV) vectored vaccine encoding type A OspC (VV-OspC-A). Two doses of the VV-OspC-A vaccine conferred complete protection against homologous B. burgdorferi challenge in mice. Furthermore, the candidate vaccine also prevented the development of carditis and lymph node hyperplasia associated with LD. When investigating the humoral immune response to vaccination, VV-OspC-A was found to induce a robust antibody response predominated by the IgG2a subtype, indicating a Th1-bias. Using a novel quantitative flow cytometry assay, we also determined that elicited antibodies were capable of inducing antibody-dependent cellular phagocytosis in vitro. Finally, we demonstrated that VV-OspC-A vaccination generated a strong antigen-specific CD4+ T-cell response characterized by the secretion of numerous cytokines upon stimulation of splenocytes with OspC peptides. This study suggests a promising avenue for LD vaccine development utilizing viral vectors targeting OspC and provides insights into the immunological mechanisms that confer protection against B. burgdorferi infection.

Cerebral vasculitis as clinical manifestation of neuroborreliosis: Pattern of vascular pathology and prognostic factors of outcome.

BACKGROUND: Neuroborreliosis is a tick-borne condition that affects the central and/or peripheral nervous system. Cerebral infarction associated with neuroborreliosis-related vasculitis has been reported in only a handful of cases. Therefore, specific patterns of vascular pathology and prognostic outcome factors are still incompletely understood. AIM: To determine the pattern of vascular pathology and prognostic outcome factors in patients with neuroborreliosis-related vasculitis. METHODS: We performed a longitudinal multicenter study between 1997 and 2022 in five academic study sites in Germany with a cumulative reference area of 1,620,000 inhabitants. All patients diagnosed with neuroborreliosis-associated cerebral vasculitis were included. The evaluation of clinical parameters, including NIH Stroke Scale (NIHSS), disability ranking (modified Rankin Scale, mRS), and neuroimaging, was performed at admission as well as after 3 and 12 months. Linear regression analysis was used to identify the independent predictors of recurrent strokes, involvement of posterior circulation, or multiple vessels. RESULTS: Patients with neuroborreliosis-related vasculitis (n = 51) were relatively young (mean age: 62 years) and displayed a predominance of vascular events within the posterior circulation (60.8%). A history of smoking was linked to recurrent strokes/TIA (64.7% vs. 23.5%; p = 0.006), strokes in multiple territories (100% vs. 35.9%; p < 0.0001), and posterior circulation events (64.5% vs. 30.0%, p = 0.017), whereas other cardiovascular risk factors showed no significant differences. Linear regression analysis corroborated smoking's association with recurrent strokes/ transient ischemic attacks (B: 0.412; p = 0.002), multiple territory strokes/TIA (B: 0.467; p = 0.033), and posterior circulation events (B: 0.317; p = 0.033). CONCLUSION: A thorough CSF examination for neuroborreliosis is crucial, especially in younger stroke patients, particularly those experiencing posterior circulation ischemic events. Smoking cessation should be prompted in patients with neuroborreliosis-associated cerebral vasculitis.

Maximizing and sustaining the efficacy of tick tubes for management of Ixodes scapularis through optimized deployment strategies.

The number of tick-borne disease cases continues to rise in the United States, with Lyme disease the most frequently reported vector-borne disease nationally. Practical and effective tick control tools and strategies are needed to reduce tick encounters and tick-borne disease risk. Tick management tubes have shown varying efficacy when used as part of a tick management plan. To evaluate factors contributing to the efficacy of tick management tubes, this study assessed changes in tick tube deployment on tick burden on wild-caught Peromyscus mice, a primary reservoir for the bacterium causing Lyme disease, in Pennsylvania from 2021 to 2023. Over 2 years, tick tubes were deployed starting at different times of the year, with cotton removal from the tubes assessed every 2 weeks from April to November and tick burden on wild-caught mice assessed every 2 months from April to October of each year. The effect of distance between tick management tubes was assessed in year 3 of this study, with mouse tick burden assessed pre- and post-treatment with tick tubes at varying intervals in a field setting. There was a significant reduction in mouse tick burden between treated and control transects, and pre- and post-treatment transects. Tick tube distance did not affect cotton removal or tick burden on mice. Still, cotton removal was highest in September-October, and amount removed increased the longer tick tubes were deployed in the field, highlighting the long-term benefits of using tick tubes as part of an integrated tick management plan. Future investigations to evaluate the impact of tick management tubes on tick nymph density and infection would be valuable for assessing the effectiveness of tick management tubes in reducing tick bite risk.

Evaluation of Lyme serologic quantitative test indexes: High first-tier test index values predict positive second-tier result in standard and modified 2-tier Lyme testing algorithms.

OBJECTIVES: In this study, we evaluated the potential utility of reporting a quantitative Lyme serologic test index to improve the utility of results from first-tier Lyme assays. METHODS: Serum from consecutive samples sent to our laboratory for Lyme testing were tested on 2 commercial first-tier Lyme assays and evaluated to determine the probability of second-tier confirmation based on the serologic index value. RESULTS: For both assays, we identified an index value above which 100% of samples confirmed on second-tier testing using both standard and modified 2-tier testing algorithms. Lower rates of confirmation were observed for positive or equivocal samples with lower index values. CONCLUSION: The use of a Lyme test index value may eliminate the need for confirmatory testing on many positive first-tier samples, providing more rapid turnaround time to a definitive result. This practice would also increase efficiency in the clinical laboratory.

Association of Borrelia burgdorferi with nuchal bursitis and elevated outer surface protein A-specific serum antibodies in horses of the northeastern United States.

OBJECTIVE: Evaluate the incidence of Borrelia burgdorferi in cases of equine nuchal bursitis (NB) and investigate the relationship between elevated serum outer surface protein A (OspA) antibodies and the molecular identification of B burgdorferi in bursal tissue or synovial fluid. Additionally, describe clinical cases and compare the histologic changes in NB with and without detection of B burgdorferi. METHODS: This was a retrospective multicenter cohort study (2013 to 2022). Medical records from horses with a diagnosis of NB and B burgdorferi PCR testing on NB tissue or synovial fluid were reviewed. The study population included 11 horses with a postmortem diagnosis of NB, 19 horses from the northeastern US with an antemortem diagnosis of B burgdorferi PCR-positive NB, and 15 healthy controls without evidence of NB and unvaccinated for B burgdorferi. Where serum was available, Lyme multiplex assay results were compared with controls and ELISAs targeting individual B burgdorferi antigens were performed. Histologic findings in nuchal bursa tissue were compared between NB cases with and without B burgdorferi PCR detection. RESULTS: Serum OspA antibody values in B burgdorferi-positive NB cases (n = 13) were significantly elevated (P < .001) compared to controls (15), and OspA was the predominant antigen detected by ELISA (8). Histopathology did not vary between NB cases with (n = 9) and without (6) B burgdorferi PCR detection. CONCLUSIONS: The presence of B burgdorferi in the nuchal bursa of horses is associated with increased serum OspA antibodies. CLINICAL RELEVANCE: The role of B burgdorferi in equine NB may be underestimated, and targeted therapy requires investigation.

Preclinical Evidence for the Protective Capacity of Antibodies Induced by Lyme Vaccine Candidate VLA15 in People.

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

Lyme Disease Under-Ascertainment During the COVID-19 Pandemic in the United States: Retrospective Study.

Background: The COVID-19 pandemic resulted in a massive disruption in access to care and thus passive, hospital- and clinic-based surveillance programs. In 2020, the reported cases of Lyme disease were the lowest both across the United States and North Carolina in recent years. During this period, human contact patterns began to shift with higher rates of greenspace utilization and outdoor activities, putting more people into contact with potential vectors and associated vector-borne diseases. Lyme disease reporting relies on passive surveillance systems, which were likely disrupted by changes in health care-seeking behavior during the pandemic. Objective: This study aimed to quantify the likely under-ascertainment of cases of Lyme disease during the COVID-19 pandemic in the United States and North Carolina. Methods: We fitted publicly available, reported Lyme disease cases for both the United States and North Carolina prior to the year 2020 to predict the number of anticipated Lyme disease cases in the absence of the pandemic using a Bayesian modeling approach. We then compared the ratio of reported cases divided by the predicted cases to quantify the number of likely under-ascertained cases. We then fitted geospatial models to further quantify the spatial distribution of the likely under-ascertained cases and characterize spatial dynamics at local scales. Results: Reported cases of Lyme Disease were lower in 2020 in both the United States and North Carolina than prior years. Our findings suggest that roughly 14,200 cases may have gone undetected given historical trends prior to the pandemic. Furthermore, we estimate that only 40% to 80% of Lyme diseases cases were detected in North Carolina between August 2020 and February 2021, the peak months of the COVID-19 pandemic in both the United States and North Carolina, with prior ascertainment rates returning to normal levels after this period. Our models suggest both strong temporal effects with higher numbers of cases reported in the summer months as well as strong geographic effects. Conclusions: Ascertainment rates of Lyme disease were highly variable during the pandemic period both at national and subnational scales. Our findings suggest that there may have been a substantial number of unreported Lyme disease cases despite an apparent increase in greenspace utilization. The use of counterfactual modeling using spatial and historical trends can provide insight into the likely numbers of missed cases. Variable ascertainment of cases has implications for passive surveillance programs, especially in the trending of disease morbidity and outbreak detection, suggesting that other methods may be appropriate for outbreak detection during disturbances to these passive surveillance systems.

Analysis of bb0556 Expression and Its Role During Borrelia burgdorferi Mammalian Infection.

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

Incidence of symptomatic Lyme borreliosis in nine European countries.

OBJECTIVES: To better understand the Lyme borreliosis (LB) burden in Europe, we aimed to estimate the incidence of symptomatic Borrelia burgdorferi sensu lato (Bbsl) infections after adjusting public health LB surveillance data for under-detection of symptomatic Bbsl infections. METHODS: Data from seroprevalence studies and estimates of the symptomatic proportion and duration of antibody detection in Bbsl-infected individuals, derived from reviews of the published literature, were used to adjust public health LB surveillance data to estimate the incidence of symptomatic Bbsl infection in nine European countries from 2018-2022. RESULTS: The prevalence of anti-Bbsl antibodies ranged from 2.3% in Romania to 9.4% in Germany. Under-detection multipliers varied across surveillance systems; using 10-year duration of antibody detection, multipliers were 2.4-10.5 in countries reporting all LB cases and 54.6-722.2 in countries reporting only Lyme neuroborreliosis cases. The incidence of symptomatic Bbsl infection adjusted for under-detection was highest in Finland, Germany, Norway, Poland, and Switzerland, intermediate in the Czech Republic and Denmark, and lowest in Ireland and Romania. CONCLUSIONS: Adjustment of LB surveillance for under-detection found a high incidence of symptomatic Bbsl infection in several European countries. Differences in LB surveillance systems should be considered when comparing surveillance data between countries and when estimating LB disease burden.

Neuroborreliosis with intracranial hypertension and visual loss in a pediatric patient: illustrative case.

BACKGROUND: Approximately 15% of Lyme disease cases involve the nervous system and are termed "neuroborreliosis." A rare complication of neuroborreliosis is idiopathic intracranial hypertension with resulting neurological deterioration. There are very few reports of this in the literature, most of which consist of case reports and small case series. Neurosurgical intervention is exceedingly rare but may be needed in select cases. OBSERVATIONS: The authors present the case of a 13-year-old male with Lyme disease and concurrent babesiosis with progressive headache, meningismus, emesis, and visual loss over several weeks. Serum and cerebrospinal fluid (CSF) testing confirmed a diagnosis of neuroborreliosis. Despite antimicrobial therapy and acetazolamide, visual loss worsened. An external ventricular drain (EVD) was urgently placed for CSF diversion. The use of CSF diversion, antimicrobial therapy, and acetazolamide led to significant improvement in the patient's symptoms with nearly complete resolution. The EVD could be weaned, and permanent CSF diversion was not needed. LESSONS: This case highlights a rare but significant complication of neuroborreliosis. Intracranial hypertension with resulting neurological deterioration, while uncommon, can occur in patients with Lyme disease. Management is most often medical, consisting of intravenous antibiotics and acetazolamide to reduce CSF production. In rare cases, temporary CSF diversion is necessary and can provide significant benefits to select patients. https://thejns.org/doi/10.3171/CASE2451.

Lyme Neuroborreliosis in the Context of Dementia Syndromes.

Lyme disease (LD) can affect the skin, joints, heart, and nervous system as a multisystemic condition. The cause of the illness is the spirochete of the genus Borrelia. These pathogens can affect the skin, joints, heart, and nervous system. Lyme neuroborreliosis (LNB) is the term for the disease, which occurs when the nervous system gets involved. Regarding geographical distribution, LNB is more prevalent in Europe than in North America. The most significant change in pathogenesis is inflammation of the central nervous system (CNS) and peripheral nervous system (PNS). Furthermore, clinically, it can represent a variety of neurological manifestations, such as meningitis, encephalitis, radiculopathies, and cranial neuritis. However, dementia-like syndrome is an infrequent manifestation of Lyme disease. Our review article aims to summarize the similarities and differences between dementia-like syndrome in LNB and that in primary neurodegenerative diseases, as well as to look for a correlation between the pathogenesis of the disease and the possibility of developing dementia-like syndrome. The world literature lacks sufficiently convincing data on the relationship between spirochete infection and primary dementia syndromes. However, cases of secondary dementia syndrome due to nervous system involvement as well as post-treatment have been described. A thorough examination, medical history, laboratory and imaging studies, cerebrospinal fluid (CSF) examination, MRI, and fludeoxyglucose-18-positron emission tomography (FGD-PET) are required to differentiate between these syndromes.