Challenges of laboratory diagnosis of Lyme disease ‒ Questionnaire survey results.

Lyme disease. Our second goal was to identify bacterial and viral co-infections occurring concurrently with Lyme disease. Furthermore, it was our intention to also analyze the correlation of laboratory testing with the occurrence of erythema migrans (EM). BACKGROUND: The accuracy in diagnostic testing for Lyme disease in the early stages of infection is an important factor necessary for delivering proper treatment to patients. METHODS: A total of 173 individuals with confirmed Lyme disease or with laboratory testing underway participated in the quantitative survey. RESULTS: ELISA was the first test conducted in 51% of the respondents, 28% of whom yielded positive findings of both IgM and IgG antibody classes. The positivity of ELISA test findings was confirmed by Western blot in 100% of results. Negative results of ELISA were consistent with Western blot only in less than half of the patients. More than half of the respondents had not been tested for any bacterial or viral co-infections. The results of serological testing were not consistent with clinical findings in all cases, including those with clinically discernible skin manifestation of erythema migrans. CONCLUSION: The comparison of results obtained by ELISA and Western blot revealed significant discrepancies. Simultaneous infections by vectors with several pathogens were detected (Tab. 3, Fig. 2, Ref. 15).

Mapping the distribution of Lyme disease at a mid-Atlantic site in the United States using electronic health data.

Lyme disease is a spatially heterogeneous tick-borne infection, with approximately 85% of US cases concentrated in the mid-Atlantic and northeastern states. Surveillance for Lyme disease and its causative agent, including public health case reporting and entomologic surveillance, is necessary to understand its endemic range, but currently used case detection methods have limitations. To evaluate an alternative approach to Lyme disease surveillance, we have performed a geospatial analysis of Lyme disease cases from the Johns Hopkins Health System in Maryland. We used two sources of cases: a) individuals with both a positive test for Lyme disease and a contemporaneous diagnostic code consistent with a Lyme disease-related syndrome; and b) individuals referred for a Lyme disease evaluation who were adjudicated to have Lyme disease. Controls were individuals from the referral cohort judged not to have Lyme disease. Residential address data were available for all cases and controls. We used a hierarchical Bayesian model with a smoothing function for a coordinate location to evaluate the probability of Lyme disease within 100 km of Johns Hopkins Hospital. We found that the probability of Lyme disease was greatest in the north and west of Baltimore, and the local probability that a subject would have Lyme disease varied by as much as 30-fold. Adjustment for demographic and ecological variables partially attenuated the spatial gradient. Our study supports the suitability of electronic medical record data for the retrospective surveillance of Lyme disease.

Study protocol for a scoping review of Lyme disease prediction methodologies.

INTRODUCTION: In the temperate world, Lyme disease (LD) is the most common vector-borne disease affecting humans. In North America, LD surveillance and research have revealed an increasing territorial expansion of hosts, bacteria and vectors that has accompanied an increasing incidence of the disease in humans. To better understand the factors driving disease spread, predictive models can use current and historical data to predict disease occurrence in populations across time and space. Various prediction methods have been used, including approaches to evaluate prediction accuracy and/or performance and a range of predictors in LD risk prediction research. With this scoping review, we aim to document the different modelling approaches including types of forecasting and/or prediction methods, predictors and approaches to evaluating model performance (eg, accuracy). METHODS AND ANALYSIS: This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines. Electronic databases will be searched via keywords and subject headings (eg, Medical Subject Heading terms). The search will be performed in the following databases: PubMed/MEDLINE, EMBASE, CAB Abstracts, Global Health and SCOPUS. Studies reported in English or French investigating the risk of LD in humans through spatial prediction and temporal forecasting methodologies will be identified and screened. Eligibility criteria will be applied to the list of articles to identify which to retain. Two reviewers will screen titles and abstracts, followed by a full-text screening of the articles' content. Data will be extracted and charted into a standard form, synthesised and interpreted. ETHICS AND DISSEMINATION: This scoping review is based on published literature and does not require ethics approval. Findings will be published in peer-reviewed journals and presented at scientific conferences.

Cutaneous borreliosis in children - a challenging problem.

Borreliosis, also known as Lyme disease, is a vector-borne disease caused by different species of the Borrelia burgdorferi complex. It is frequent in Europe and Northern America. The major vectors are ixodoid ticks. Paediatric borreliosis is common and peaks in children between five to nine years. In Europe, the leading symptom of early infection is erythema migrans, in contrast to Northern America where arthritis is the dominating clinical finding. In this review, we focus on Europe, where cutaneous borreliosis is mainly caused by infection with B. afzelii. The cutaneous symptoms include erythema migrans, lymphocytoma, chronic atrophic dermatitis and juxta-articular nodules. In children, lymphocytoma is very common but chronic atrophic dermatitis is rare. Clinical symptoms, diagnosis, peculiarities of childhood disease and treatment are also reviewed. It is important to note that after haematogeneic spread, signs of infection may be non-specific, and this is a challenge for diagnosis.

[High-degree atrioventricular (AV) block]. / Borreliakardit ­ ovanlig orsak till atrioventrikulärt block.

In elderly patients high-degree atrioventricular (AV) block is often due to irreversible degeneration of the cardiac conduction system. Reversible causes must however be excluded prior to pacemaker implantation. In younger patients reversible causes are more likely, as well as more unusual etiologies. Lyme carditis is a rare, but reversible cause of AV block. It is a manifestation of Lyme borreliosis - an infectious disease caused by the bacteria Borrelia burgdorferi. Lyme carditis should particularly be considered in young and middle-aged patients with a high-degree AV block. When pretest probability is intermediate to high, a positive serological test makes the diagnosis of Lyme carditis highly likely. In these cases antibiotic treatment may revert the conduction disturbance, thus preventing unnecessary implantation of a permanent pacemaker.

[Cutaneous Lyme disease: not always a rash with a central clearing]. / Cutane lymeziekte: lang niet altijd een rode ring.

During the past four decades the number of reported Lyme disease diagnoses in the Netherlands has increased to 27.000 a year, with a yearly incidence of Lyme disease between 111 (95% CI 106-115) to 131 (95% CI 126-136) per 100,000 person years. A large part of all Lyme disease diagnoses concern the skin; in the Netherlands, 77-89% erythema migrans, 2-3% borrelia lymfocytoom and 1-3% acrodermatitis chronica atrophicans. These skin manifestations have a variable clinical expression, reason why they can be difficult to diagnose. Early recognition and treatment is important to prevent the development of systemic manifestations.

Performance of two modified two-tier algorithms for the serologic diagnosis of Lyme disease.

We compared the performance of a new modified two-tier testing (MTTT) platform, the Diasorin Liaison chemiluminescent immunoassay (CLIA), to the Zeus enzyme-linked immunoassay (ELISA) MTTT and to Zeus ELISA/Viramed immunoblot standard two-tier testing (STTT) algorithm. Of 537 samples included in this study, 91 (16.9%) were positive or equivocal by one or more screening tests. Among these 91 samples, only 57 samples were concordant positive by first-tier screening tests, and only 19 of 57 were concordant by the three second-tier methods. For IgM results, positive percent agreement (PPA) was 68.1% for Diasorin versus 89.4% for Zeus compared to immunoblot. By contrast, the PPA for IgG for both Diasorin and Zeus was 100%. Using a 2-out-of-3 consensus reference standard, the PPAs for IgM were 75.6%, 97.8%, and 95.6% for Diasorin, Zeus, and immunoblot, respectively. The difference between Zeus MTTT and Diasorin MTTT for IgM detection was significant (P = 0.0094). PPA for both Diasorin and Zeus MTTT IgG assays was 100% but only 65.9% for immunoblot STTT (P = 0.0005). In total, second-tier positive IgM and/or IgG results were reported for 57 samples by Diasorin MTTT, 63 by Zeus MTTT, and 54 by Viramed STTT. While Diasorin CLIA MTTT had a much more rapid, automated, and efficient workflow, Diasorin MTTT was less sensitive for the detection of IgM than Zeus MTTT and STTT including in 5 early Lyme cases that were IgM negative but IgG positive. IMPORTANCE: The laboratory diagnosis of Lyme disease relies upon the detection of antibodies to Borrelia species. Standard two tier testing (STTT) methods rely upon immunoblots which have clinical and technical limitations. Modified two-tier testing (MTTT) methods have recently become available and are being widely adopted. There are limited independent data available assessing the performance of MTTT and STTT methods.

A prospective study of patients with post treatment Lyme disease syndrome treated with modified VFEM energy.

BACKGROUND: We previously demonstrated a possible therapeutic benefit of VFEM (variable frequency electromagnetic energy) technology for the treatment of Post Treatment Lyme Disease Syndrome (PTLDS) or Chronic Lyme Disease (CLD). As a result, we prospectively enrolled 10 patients, all having significant debility, to determine to what extent we could improve their quality of life. Eight patients completed the 10 treatments. RESULTS: All eight patients had a significant improvement in quality of life within a 4-month time frame. CONCLUSION: VFEM is a stand-alone modality that appears to demonstrate a significant improvement in quality of life in PTLDS or CLD with little or no risk or side effects of treatment.

Retrospective validation of a rapid Lyme fluorescent immunoassay in differentiating Lyme arthritis from other musculoskeletal presentations in children in a Lyme-endemic region.

Lyme arthritis can present similarly to other causes of joint pain and swelling including septic arthritis and other acute and chronic arthropathies of childhood. Septic arthritis, although rare, constitutes an orthopedic emergency and requires early surgical intervention to reduce the risk of permanent joint damage. Currently, results of standard serologic tests to diagnose Lyme disease take days to weeks, which is unhelpful in acute clinical decision-making. Thus, some children with Lyme arthritis are treated empirically for septic arthritis undergoing unnecessary invasive procedures and hospital admission while on inappropriate antibiotic therapy. We retrospectively validated the Quidel Sofia Lyme Fluorescent Immunoassay, a rapid serologic assay that can detect IgG and/or IgM antibodies to Borrelia burgdorferi in 10 minutes, in residual serum samples collected from 51 children who had Lyme arthritis and 55 children with musculoskeletal presentations who were Lyme negative. The sensitivity and specificity of the Sofia IgG to identify cases of Lyme arthritis in children were 100% (95% confidence interval [CI] of 93.0%-100%) and 96.4% (95% CI: 87.5%-99.6%), respectively. The positive likelihood ratio (LR) was 27.5 (95% CI 7-107), and the negative LR was 0.00 (95% LR 0.00-0.15). We propose that the Sofia IgG, a rapid method for identifying Lyme arthritis, may be useful in differentiating Lyme arthritis from other forms of arthritis. Used in conjunction with readily available clinical and laboratory variables, it could help to rapidly identify children who are at low risk of septic arthritis in Lyme-endemic regions. IMPORTANCE: Lyme arthritis is a common manifestation of Lyme disease in children, with clinical features overlapping with other causes of acute and chronic joint pain/swelling in children. We have demonstrated that the Sofia IgG is a reliable test to rule in and rule out the diagnosis of Lyme arthritis in children with musculoskeletal presentations in a Lyme-endemic region. When used in conjunction with clinical and laboratory variables routinely considered when differentiating Lyme arthritis from other diagnoses, the Sofia IgG has the potential to fill an important gap in care, especially when acute decision-making is necessary. The Sofia IgG should be included in prospective research studies examining clinical prediction tools to identify children at low risk of septic arthritis.

Cranial nerve involvement, visual complications and headache syndromes in Lyme disease.

PURPOSE OF REVIEW: To provide a summary of the visual manifestations and cranial neuropathies seen in Lyme disease. RECENT FINDINGS: Lyme facial palsy remains the most common manifestation of Lyme neuroborreliosis. Recent investigations show likely evidence of vagal involvement in Lyme disease. SUMMARY: The literature on Lyme neuroborreliosis continues to evolve. Lyme disease can affect nearly any cranial nerve in addition to causing various headache syndromes. The most common manifestation is Lyme disease facial palsy, occurring in up to 5-10% of patients with documented Lyme disease. Headache syndromes are common in the context of facial palsy but can occur in isolation, and more specific headache syndromes including trigeminal and geniculate neuralgias can occur rarely. Signs and symptoms indicative of vestibulocochlear nerve involvement are relatively common, although it could be that these represent other vestibular involvement rather than a specific cranial neuropathy. Optic neuritis is a controversial entity within Lyme disease and is likely overdiagnosed, but convincing cases do exist. Physicians who see any cranial neuropathy, including optic neuritis, in an endemic area can consider Lyme disease as a possible cause.

Seroprevalence of Infection by Borrelia Species Responsible for Lyme Disease in the French Alps: Analysis of 27,360 Serology Tests, 2015-2020.

Objectives: Lyme borreliosis incidence is increasing in several areas; moreover, it has recently gained the public's attention. Apart from erythema migrans, Lyme disease diagnosis relies (among others) on serology test; however, the prevalence of positive enzyme-linked immunosorbent assay (ELISA) and western blot (WB) assay has been poorly studied in the general population. We aimed to approach the seroprevalence of infection by Borrelia species responsible for Lyme disease in the French Isere department using city laboratories data. Patients and Methods: We retrieved all serological tests for Borrelia species responsible for Lyme disease performed in the two main networks of city laboratories between 2015 and 2020. All patients with both ELISA and WB IgG were considered seropositive. Results: We analyzed 27,360 tests (ELISA/ELISA+WB). Mean age was 50.9 ± 20.3 years (ranges: 0-101), with 57.1% females. Overall, 11.7% had IgG detected by ELISA, and 4.7% had IgG detected by both ELISA and WB assay. Seropositive status was more frequent in males (7.0% vs. 2.9%, p < 0.001). Seropositivity rate increased with age after a first peak in childhood; men aged 61-70 years had the highest seropositivity rate (10.3%). In addition, seropositivity rate was higher in persons from a rural area. In multivariate analysis, older age, male gender and living in a rural area were independently associated with seropositivity. Seropositivity rate was stable on the 2017-2020 period. Conclusion: The seroprevalence of infection by Borrelia species responsible for Lyme disease is high in Isere; this probably reduces the predictive positive value for Lyme disease of ELISA and WB IgG, suggesting that this serological test should not be performed for nonspecific symptoms.

Parálisis facial, la importancia de realizar una buena historia clínica / Facial palsy, the importance of taking a good medical history

La parálisis facial plantea un diagnóstico diferencial amplio en Pediatría, sobre todo cuando se acompaña de sintomatología que orienta en contra de una parálisis de Bell, por lo que resulta imprescindible realizar una correcta anamnesis. La enfermedad de Lyme es una de las posibles causas de parálisis facial, habiendo sido poco descrita en niños en España. Presentamos el caso de un varón de 11 años con diagnóstico de parálisis facial asociada a infección por B. burgdorferi con evolución favorable tras tratamiento con doxiciclina. (AU)

Facial palsy poses a wide differential diagnosis in pediatrics, especially when it is accompanied by symptoms that make it doubtful whether Bell's palsy is present. It is essential to perform a correct anamnesis to rule out diagnoses that require early detection and treatment to improve the prognosis. Lyme disease (EL) is one of the possible causes of facial palsy, having been seldom described in children in Spain. We present the case of an 11-years-old male with diagnosis of facial palsy associated with B. burgdorferi infection with favorable evolution after treatment with doxycycline. (AU)

Evaluation and 1-year follow-up of patients presenting at a Lyme borreliosis expertise centre: a prospective cohort study with validated questionnaires.

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.

Comparative evaluation of Borrelia burgdorferi antibody detection between the VetScan Flex4 and SNAP 4Dx Plus.

Two studies were developed to compare Borrelia burgdorferi antibody detection between the VetScan Flex4 and SNAP 4Dx Plus tests. The objective of the first study was to evaluate the diagnostic sensitivity (Se) and specificity (Sp) of VetScan Flex4 and SNAP 4Dx Plus B. burgdorferi results using field sourced samples compared to a Western Blot reference method. The sensitivity and specificity of VetScan Flex4 were 81.9 % (95 % CI: 71.9 %-89.5 %) and 89.3 % (95 % CI: 85.2 %-92.9 %) respectively, and SNAP 4Dx Plus's sensitivity and specificity were 80.7 % (95 % CI: 70.6 %-88.6 %) and 92.8 % (95 % CI: 89.1 %-95.5 %) respectively. When comparing VetScan Flex4 and Snap 4Dx Plus, the Simple Kappa Coefficient estimate was 0.76 (95 % CI: 0.69-0.84) indicating substantial agreement between the two methods. McNemar's Test revealed concordance between the two methods was not statistically significant (P = 0.05). The objective of the second study was to evaluate whether VetScan Flex4 differentiates between B. burgdorferi antibodies derived from infection versus vaccination with commonly used canine Lyme vaccines. The sensitivity and specificity of the VetScan Flex4 in differentiating canine Lyme vaccination from infection with Borrelia burgdorferi were 100 % (Se 95 % CI: 78.2 %-100 %; Sp 95 % CI: 91.2 %-100 %). In conclusion, the VetScan Flex4 is a reliably sensitive and specific point-of-care test that is similar to Snap 4Dx Plus, can differentiate between infection and Lyme vaccination, and can be utilized by veterinarians for Lyme disease diagnosis and surveillance of B. burgdorferi exposure.

Antibodies to Borrelia burgdorferi and Bartonella species in serum and synovial fluid from people with rheumatic diseases.

Vector-borne infections may underlie some rheumatic diseases, particularly in people with joint effusions. This study aimed to compare serum and synovial fluid antibodies to B. burgdorferi and Bartonella spp. in patients with rheumatic diseases. This observational, cross-sectional study examined paired synovial fluid and serum specimens collected from 110 patients with joint effusion between October 2017 and January 2022. Testing for antibodies to B. burgdorferi (using CDC criteria) and Bartonella spp. via two indirect fluorescent antibody (IFA) assays was performed as part of routine patient care at the Institute for Specialized Medicine (San Diego, CA, USA). There were 30 participants (27%) with positive two-tier B. burgdorferi serology and 26 participants (24%) with IFA seroreactivity (≥1:256) to B. henselae and/or B. quintana. Both B. burgdorferi IgM and IgG were detected more frequently in synovial fluid than serum: 27% of patients were either IgM or IgG positive in synovial fluid, compared to 15.5% in serum (P = 0.048). Conversely, B. henselae and B. quintana antibodies were detected more frequently in serum than synovial fluid; overall only 2% of patients had positive IFA titers in synovial fluid, compared to 24% who had positive IFA titers in serum (P < 0.001). There were no significant associations between B. burgdorferi or Bartonella spp. seroreactivity with any of the clinical rheumatological diagnoses. This study provides preliminary support for the importance of synovial fluid antibody testing for documenting exposure to B. burgdorferi but not for documenting exposure to Bartonella spp. IMPORTANCE: This study focuses on diagnostic testing for two common vector-borne diseases in an affected patient population. In it, we provide data showing that antibodies to B. burgdorferi, but not Bartonella spp., are more commonly found in synovial fluid than serum of patients with joint effusion. Since Lyme arthritis is a common-and sometimes difficult to diagnose-rheumatic disease, improving diagnostic capabilities is of utmost importance. While our findings are certainly not definitive for changes to practice, they do suggest that synovial fluid could be a useful sample for the clinical diagnosis of Lyme disease, and future prospective studies evaluating this claim are warranted.

Lyme disease and Whipple's disease: a comprehensive review for the rheumatologist.

Despite their rarity, Lyme disease and Whipple's disease are of significant importance in rheumatology, as both can manifest as chronic arthritis, presenting challenges in the differential diagnosis of inflammatory arthropathies. In Lyme disease, arthritis typically emerges as a late manifestation, usually occurring six months after the onset of erythema migrans. The predominant presentation involves mono- or oligoarthritis of large joints, with a chronic or remitting-recurrent course. Even with appropriate antimicrobial treatment, arthritis may persist due to inadequate immunological control triggered by the disease. In contrast, Whipple's disease may present with a migratory and intermittent seronegative poly- or oligoarthritis of large joints, preceding classic gastrointestinal symptoms by several years. Both disorders, particularly Whipple's disease, can be misdiagnosed as more common autoimmune rheumatic conditions such as rheumatoid arthritis and spondyloarthritis. Epidemiology is crucial in suspecting and diagnosing Lyme disease, as the condition is transmitted by ticks prevalent in specific areas of the United States, Europe, and Asia. On the contrary, the causative agent of Whipple's disease is widespread in the environment, yet invasive disease is rare and likely dependent on host genetic factors. In addition to erythema migrans in Lyme disease and gastrointestinal manifestations in Whipple's disease, neurological and cardiac involvement can further complicate the course of both. This article offers a comprehensive review of the epidemiological, pathophysiological, clinical, and therapeutic aspects of both diseases.

Lyme borreliosis and medical wandering: what do patients think about multidisciplinary management? A qualitative study in the context of scientific and social controversy.

INTRODUCTION: To answer to patients' medical wandering, often due to "unexplained symptoms" of "unexplained diseases" and to misinformation, multidisciplinary care centers for suspected Lyme borreliosis (LB), such as the 5 Tick-Borne Diseases (TBDs) Reference Centers (TBD-RC), were created a few years ago in France, the Netherlands and Denmark. Our study consisted of a comprehensive analysis of the satisfaction of the patients managed at a TBD-RC for suspected LB in the context of scientific and social controversy. METHODS: We included all adults who were admitted to one of the TBD-RC from 2017 to 2020. A telephone satisfaction survey was conducted 12 months after their first consultation. It consisted of 5 domains, including 2 free-text items: "What points did you enjoy?" and "What would you like us to change or to improve?". In the current study, the 2 free-items were analyzed with a qualitative method called reflexive thematic analysis within a semantic and latent approach. RESULTS: The answer rate was 61.3% (349/569) and 97 distinctive codes from the 2-free-text items were identified and classified into five themes: (1) multidisciplinarity makes it possible to set up quality time dedicated to patients; (2) multidisciplinarity enables seamless carepaths despite the public hospital crisis compounded by the COVID-19 pandemic; (3) multidisciplinarity is defined as trust in the team's competences; (4) an ambivalent opinion and uncertainty are barriers to acceptance of the diagnosis, reflecting the strong influence of the controversy around LB; and (5) a lack of adapted communication about TBDs, their management, and ongoing research is present. CONCLUSION: The multidisciplinary management for suspected LB seemed an answer to medical wandering for the majority of patients and helped avoid misinformation, enabling better patient-centered shared information and satisfaction, despite the context of controversy.

Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications.

BACKGROUND: Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms. METHODS: We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients-divided into a discovery and validation cohort-were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments. RESULTS: We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses. CONCLUSIONS: Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures. TRIAL REGISTRATION: The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015-02-13).