Search Results (52)

Background: Lyme borreliosis is a multisystemic tick-borne infection caused by Borrelia burgdorferi sensu lato complex. Renal involvement is well documented in dogs with Lyme nephritis, whereas human renal manifestations have been reported only rarely, mainly as isolated case reports of glomerular disease. Because a proportion of chronic kidney disease (CKD) cases remain unexplained, we aimed to determine the possible contribution of previous exposure to idiopathic CKD. Methods: The study included 45 patients and 45 age and sex matched controls. Serum samples were tested for anti-Borrelia IgG using enzyme-linked immunosorbent assay (ELISA). Positive or borderline ELISA results were further evaluated by Western blot (WB) analysis. Results: Overall, anti-Borrelia IgG seropositivity was 5.55% with WB. In the CKD group, ELISA positivity was 11.1% and WB-confirmed positivity was 8.9%. In the control group, ELISA positivity was 4.4% and WB-confirmed positivity was 2.2%. (p > 0.05). All confirmed patients were living in rural areas, engaged in farming and/or animal husbandry, and reported repeated tick exposure. Conclusions: IgG seropositivity was numerically higher among patients with CKD of unknown etiology than among healthy controls; however, this difference was not statistically significant. Larger, risk-factor-adjusted studies are needed to clarify whether Borrelia exposure may be associated with unexplained CKD. Full article

Patients with Lyme disease often face uncertainty when navigating the healthcare system during pregnancy and when seeking healthcare for their children exposed to Lyme disease in utero. Little is known about these families’ experiences. This qualitative study explored the perspectives of 27 parents in the United States who had acute or chronic Lyme-related diagnoses while pregnant. Semi-structured interviews were coded and thematically analyzed. Six themes characterized positive patient–physician interactions: (1) validation of patient experiences, (2) transparency, (3) willingness to learn, (4) shared decision making, (5) empathy, and (6) continuity of care. These findings offer guidance for clinicians counseling patients facing prognostic uncertainty related to Lyme disease and similarly complex conditions. Full article

Background and Aim: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation. Environmental factors, including infectious agents, have been proposed to influence disease activity in inflammatory bowel disease. Although Borrelia burgdorferi has been shown to exert complex immunomodulatory effects on host immune responses, its seroprevalence and potential association with disease activity in patients with ulcerative colitis have not been systematically investigated. This study aimed to evaluate the seroprevalence of Borrelia burgdorferi IgG antibodies in patients with ulcerative colitis and to assess the relationship between seropositivity and laboratory markers of disease activity. Methods: In this retrospective observational study, 100 patients with ulcerative colitis (59 males, 41 females; mean age 48.5 ± 17 years) who underwent Borrelia burgdorferi IgG serological testing due to musculoskeletal or neurological symptoms suggestive of possible Lyme disease between October 2020 and October 2024 were included. Demographic characteristics, hematological and biochemical parameters, and inflammatory markers were compared between seropositive and seronegative groups. Due to the retrospective design, validated clinical disease activity indices were not consistently available; therefore, disease activity was indirectly assessed using laboratory inflammatory markers. Results: Among patients with ulcerative colitis, 22% were seropositive for Borrelia burgdorferi IgG. Seropositive patients had significantly lower uric acid, alkaline phosphatase, and C-reactive protein levels compared to seronegative patients (p = 0.001, p = 0.023, and p = 0.020, respectively). Free T4 levels were significantly higher in the seropositive group (p = 0.049). In terms of erythrocyte indices, mean corpuscular volume and mean corpuscular hemoglobin were significantly higher, while RDW-CV values were significantly lower in seropositive patients (all p < 0.05). Conclusion:Borrelia burgdorferi IgG seropositivity in patients with ulcerative colitis was associated with lower laboratory markers of systemic inflammation and a more stable hematological profile. Although causality cannot be established, these findings may suggest a potential association between prior Borrelia exposure and a distinct inflammatory phenotype in UC; however, this relationship should be interpreted with caution. Further prospective and mechanistic studies are warranted to clarify the potential immunological interactions between environmental microbial exposure and inflammatory bowel disease activity. Full article

Introduction: Ischemic stroke in young adults is uncommon and is frequently associated with rare etiologies, including autoimmune diseases and vasculitis. Takayasu arteritis (TA) is a chronic inflammatory large-vessel arteriopathy involving the aorta and its major branches and may result in cerebral ischemia due to arterial stenosis or thrombosis. Case Presentation: We report the case of a 26-year-old woman with a history of suspected rheumatoid arthritis and Lyme disease who presented with acute left-sided hemiparesis and dysarthria. At admission, large-vessel vasculitis had not yet been suspected, and the patient was treated according to standard acute stroke protocols. Computed tomography angiography (CTA) revealed occlusion of the right middle cerebral artery bifurcation and the right common carotid artery, with inflammatory changes involving the brachiocephalic trunk and subclavian arteries. Intravenous thrombolysis (iv rtPA) was followed by mechanical thrombectomy (MT), resulting in neurological improvement. Outcome: Further diagnostic work-up confirmed TA, and immunosuppressive therapy with cyclophosphamide and infliximab was initiated. Conclusion: This case underscores the importance of considering inflammatory large-vessel disease in young patients presenting with acute ischemic stroke and illustrates that endovascular reperfusion may be feasible in this clinical setting. Full article

The cause of chronic neurological effects associated with Lyme disease (LD) remains unclear. We propose that bacterial extracellular vesicles (BEVs) released by Borrelia burgdorferi, the causative agent of LD, exacerbate spirochete-induced damage and serve as a persistent source of antigenic stimulation. We showed that, over a 10-day period, in vitro cultures of B. burgdorferi B31 produced 38,000 BEVs per spirochete with a distinctive double-membrane structure and median diameter of 143.3 nm. BEVs contained known immunogenic and immunomodulatory molecules such as peptidoglycan, p66, flagellar filament protein (FlaB), basic membrane proteins A/B/D, BdrV, GroEL, CRASP-1, ErpA8, glycerophosphodiester phosphodiesterase, p37, OMS28, p13, OspA/B/C, VlsE, and outer membrane glycolipids (e.g., cholesteryl 6-O acyl beta D galactopyranoside). Chromosome-encoded 16S ribosomal RNA and cp32 plasmid-encoded OspE and terminase genes were also detected in the BEVs. Of the 45 Borrelia proteins identified in the urine of a C3H/HeJ murine model of Lyme disease, 14 were associated with BEVs. In human urine samples, 31 of 289 spirochete proteins detected in patients with either acute Lyme disease or persistent borreliosis post-treatment symptoms, including p66 and FlaB, were also BEV-associated. BEV treatment of HMC3 human microglial cells reduced phagocytic activity and triggered aberrant activation of inflammatory and immunometabolic pathways, including upregulation of interferon-alpha (IFN-α), aconitate decarboxylase 1 (Acod1), and Toll-like receptor 2 (TLR2) gene expression. BEVs also induced NRF2 nuclear translocation. In conclusion, these findings support that BEVs can amplify spirochete-induced damage and act as antigenic debris, driving dampened phagocytic activity and dysregulated inflammation, with implications for diagnostics and therapeutics targeting vesicle-mediated pathology. Full article

Background: COVID-19 has taken millions of lives and continues to affect people worldwide. Post-Acute Sequelae of SARS-CoV-2 Infection (also known as Post-Acute Sequelae of COVID-19 (PASC) or more commonly, Long COVID) occurs in the aftermath of COVID-19 and is poorly understood despite its widespread effects. Methods: We created a machine-learning model that distinguishes PASC from PASC-similar diseases. The model was trained to recognize PASC-dysregulated metabolites (p ≤ 0.05) using molecular descriptors. Results: Our multi-layer perceptron model accurately recognizes PASC-dysregulated metabolites in the independent testing set, with an AUC-ROC of 0.8991, and differentiates PASC from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, postural orthostatic tachycardia syndrome (POTS), and irritable bowel syndrome (IBS). However, it was unable to differentiate fibromyalgia (FM) from PASC. Conclusions: By creating and testing models pairwise on each of these diseases, we elucidated the unique strength of the similarity between FM and PASC relative to other PASC-similar diseases. Our approach is unique to PASC diagnosis, and our use of molecular descriptors enables our model to work with any metabolite where molecular descriptors can be identified, as these descriptors can be generated and compared for any metabolite. Our study presents a novel approach to PASC diagnosis that partially circumvents the lengthy process of exclusion, potentially facilitating faster interventions and improved patient outcomes. Full article

Autonomic nervous system (ANS) dysfunction has emerged as a central feature of post-infectious syndromes, including post-COVID syndrome (PCS), chronic fatigue syndrome (CFS), and late-stage Lyme disease. This cross-sectional study included 1036 patients evaluated in the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje,” divided into four groups: PCS, CFS after COVID-19, CFS of insidious onset, and Lyme disease. All patients underwent head-up tilt testing (HUTT), and serological testing was performed in accredited institutions. The Lyme disease group demonstrated the highest prevalence of positive HUTT responses and a significantly greater frequency of orthostatic hypotension and syncope. Approximately 50–65% of patients in the PCS and Lyme groups were positive for IgM antibodies against at least one microorganism, with more than 10% showing positivity for three or more pathogens. Logistic regression analysis revealed that, beyond classical hemodynamic parameters, antibody status served as a significant predictor of HUTT outcomes, with specific associations identified for HSV-1, HHV-6, Coxiella burnetii, Toxoplasma gondii, and Borrelia spp. Multinomial regression further indicated that negative IgG antibodies, particularly to HSV-1 and VZV, predicted Lyme disease group membership. These findings support the hypothesis that ANS dysfunction in post-infectious syndromes may be driven by persistent or prior infections, highlighting the need for integrative diagnostic approaches. Full article

Introduction: Acrodermatitis chronica atrophicans (ACA) is a late-stage cutaneous manifestation of Lyme borreliosis, primarily caused by Borrelia afzelii. It mainly affects the distal limbs and leads to progressive skin atrophy. Unlike other Lyme disease rashes, ACA does not resolve on its own and can worsen into severe atrophy and fibrosis if left untreated. Diagnosing ACA can be difficult due to its delayed onset and subtle symptoms, requiring clinical evaluation, multiple blood tests, and skin biopsy. Case presentation: We present the case of a 48-year-old female with a history of pulmonary sarcoidosis who presented to our clinic with multiple erythemato-violaceous patches over her left lower leg and was initially misdiagnosed with venous insufficiency. Histopathological and serological analyses confirmed ACA in its inflammatory phase. The patient responded well to a 30-day course of doxycycline, achieving complete resolution. This report underscores the importance of considering ACA in differential diagnoses and provides a comprehensive review of its pathogenesis, clinical progression, histopathological features, and epidemiology. Conclusions: This case emphasizes the need to consider acrodermatitis chronica atrophicans (ACA) in the differential diagnosis of chronic skin lesions. Clinicians should maintain a high index of suspicion for ACA, particularly in atypical presentations. When the diagnosis is uncertain but clinical suspicion persists, skin biopsy is recommended for histopathologic confirmation. Early diagnosis and appropriate antibiotic therapy are essential to prevent disease progression and irreversible cutaneous atrophy. Accurate diagnosis and effective management require a multidisciplinary approach, involving close collaboration between dermatologists, pathologists, and infectious disease specialists. Full article

Lyme disease (LD), caused by the spirochete Borrelia burgdorferi, is the most prevalent tick-borne disease in Europe, including Romania, where endemic areas are well documented. It has a wide range of clinical manifestations and severity, including rare neurological complications. Persistent hyponatremia is an atypical presentation of Lyme neuroborreliosis and can be associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH is characterized by unregulated antidiuretic hormone release, leading to impaired water excretion, dilutional hyponatremia, and low serum osmolality. We report the case of a 16-year-old female with clinically well-tolerated, but severe, refractory hyponatremia, who was poorly responsive to intravenous sodium supplementation and fluid management. Complex investigations ruled out multiple causes of hyponatremia; neuroborreliosis was confirmed via positive Borrelia serologies, despite the absence of a suggestive history of exposure. SIADH likely symptomatology resulted from central nervous system inflammation induced by Borrelia, a mechanism rarely documented in the medical literature. Treatment with antibiotics and fluid restriction led to a gradual improvement in fluid balance and sodium homeostasis. This case emphasizes the importance of considering rare infectious causes, such as LD, in patients with unexplained SIADH, especially in endemic areas. It highlights the importance of a multidisciplinary approach in intricate, complex cases. Full article

Background/Objectives: Post-infectious syndromes, including Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease, are associated with overlapping clinical features and autonomic dysfunction. Despite shared symptoms such as fatigue and orthostatic intolerance, the underlying pathophysiology and specific patterns of autonomic dysfunction may differ. This study aimed to evaluate and compare autonomic nervous system function in these syndromes using multiple diagnostic modalities to identify unique characteristics and improve differentiation between these conditions. Methods: This cross-sectional study included 758 patients, which were divided into four groups: Post-COVID syndrome, Chronic Fatigue Syndrome following Post-COVID syndrome, Chronic Fatigue Syndrome unrelated to COVID-19, and late-stage Lyme disease. Autonomic nervous system function was assessed using cardiovascular reflex tests, the Head-Up Tilt Test, beat-to-beat analysis, five-minute electrocardiogram recordings, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses compared parameters across the groups, focusing on patterns of sympathetic and parasympathetic dysfunction. Results: The patients with Lyme disease showed distinct autonomic patterns, including a higher prevalence of orthostatic hypotension (53.4%) and changes in heart rate variability during the Head-Up Tilt Test suggestive of adrenergic failure. Compared to the other groups, patients with Lyme disease exhibited reduced baroreceptor sensitivity and diminished changes in frequency domain heart rate variability parameters during orthostatic stress. Parasympathetic dysfunction was less prevalent in the Lyme disease group, while the Post-COVID syndrome and Chronic Fatigue Syndrome groups showed more pronounced autonomic imbalances. Conclusions: The patients with Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease exhibited varying degrees and types of autonomic dysfunction. Late-stage Lyme disease is characterized by adrenergic failure and distinct hemodynamic responses, differentiating it from other syndromes. The functional assessment of autonomic nervous system function could aid in understanding and managing these conditions, offering insights for targeted therapeutic interventions. Full article

Background/Objectives: Although eligibility criteria for clinical trials significantly impact study outcomes, these criteria are often established without scientific justification, leading to delayed recruitment, small sample sizes, and limited study generalizability. Persistent Lyme disease (PLD) presents unique challenges due to symptom variability, inconsistent treatment responses, and the lack of reliable biomarkers, underscoring the need for scientifically justified eligibility criteria. Objective: This study examines the effects of commonly used enrollment criteria on sample yield in PLD clinical trials using real-world data (RWD) from the MyLymeData patient registry. The study also compares the effects of these criteria on enrollment for PLD versus acute Lyme disease (ALD) trials and evaluates the scientific rationale for each criterion. Methods: Data from 4183 Lyme disease patients enrolled in the MyLymeData registry were analyzed to assess the prevalence and cumulative impact of various criteria on sample yield. A comparative analysis of cohorts with PLD (n = 3589) versus ALD (n = 594) was conducted to identify differences in sample attrition. Results: In a large PLD cohort study, we found that current commonly used eligibility criteria would exclude approximately 90% of patients, significantly limiting study generalizability. Substantial differences in sample attrition between PLD and ALD cohorts highlight the need for tailored criteria. The strength of scientific justification varied widely among criteria. Conclusions: This study demonstrates the importance of using RWD to optimize eligibility criteria in PLD clinical trials. By providing insights into the balance between sample attrition and scientific justification, researchers can enhance trial feasibility, generalizability, and robustness. Our RWD sample demonstrates that researchers could substantially increase the sample yield from 10% to 64% by loosening restrictions on coinfections and misdiagnoses of chronic fatigue syndrome, fibromyalgia syndrome, and psychiatric conditions. Full article

Lyme disease is the most common vector-borne disease in the United States. Recent environmental and socioecological changes have led to an increased incidence of Lyme and other tick-borne diseases, which enhances the urgency of identifying and mitigating adverse outcomes of Lyme disease exposure. Lyme disease during pregnancy, especially when untreated, may lead to adverse pregnancy and neonatal outcomes; however, long-term child outcomes following utero exposure to Lyme disease have not yet been systematically assessed. This concise review describes the current state of knowledge of Lyme disease as a congenital infection and the potential effects of in utero exposure to Lyme disease infection on the neurodevelopment of infants and children. We highlight the importance of distinguishing between acute Lyme disease and a chronic condition termed Post-Treatment Lyme Disease Syndrome, as the impacts of both conditions on the developing fetus and subsequent child development may differ. The importance of placental pathology for patients with acute or chronic symptoms of Lyme disease in pregnancy is explored. Future research aiming to understand and protect neurodevelopment after antenatal Lyme disease must carefully collect potentially confounding variables such as symptomatology and treatment, use clear and standard case definitions, and follow children into school-age and beyond. Full article

Compared to classic Lyme disease (LD), Baggio–Yoshinari syndrome (BYS) has the following distinctive characteristics: it is transmitted in the Amazon area and Northeast, Central-West, Southeast, and South regions of Brazil by hard ticks, notably Amblyomma cajannense or Rhipicefalus sp. The absence of Ixodes sp. ticks in areas at risk of BYS in Brazil is probably the main reason for the disease’s differences from LD in the United States, Europe, and Asia. Biodiversity and climate probably favor the formation of atypical pleomorphic Borrelias, which have not yet been cultivated or isolated. Clinically, the first manifestation of BYS is the erythema migrans as in the classic forms of Lyme disease, but BYS is distinguished from LD by its prolonged clinical evolution, with a high frequency of relapses and the appearance of autoimmune manifestations. Prevalent symptoms are headache and erythema nodosum. Five clinical cases of BYS in patients who contracted the disease in the Brazilian Amazon rainforest are described here. This syndrome should be considered among differential diagnoses in patients bitten by ticks in Brazil who present with erythema migrans and/or headache. It is important to pursue an early diagnosis because symptoms respond well to antibiotics in the early stages; if treatment is started late, a chronic course with articular and neurological sequelae can be detected. Full article

Lyme disease is the most commonly reported vector-borne disease in the United States. Bartonella constitute an additional zoonotic pathogen whose public health impact and diversity continue to emerge. Rapid, sensitive, and specific detection of these and other vector-borne pathogens remains challenging, especially for patients with persistent infections. This report describes an approach for DNA extraction and PCR testing for the detection of Bartonella spp. and Borreliella spp. from dry blood spot (DBS) specimens from human patients. The present study included extraction of DNA and PCR testing of DBS samples from 105 patients with poorly defined, chronic symptoms labeled as Lyme-Like Syndromic Illness (LLSI). Bartonella spp. DNA was detected in 20/105 (19%) and Borreliella spp. DNA was detected in 41/105 (39%) patients with LLSI. Neither group of organisms was detected in DBS samples from 42 healthy control subjects. Bartonella spp. 16S–23S rRNA internal transcribed spacer sequences were highly similar to ones previously identified in yellow flies, lone star ticks, a human patient from Florida, mosquitoes in Europe, or B. apihabitans and choladocola strains from honeybees. These human strains may represent new genetic strains or groups of human pathogenic species of Bartonella. The 41 Borreliella spp. flaB gene sequences obtained from human patients suggested the presence of four different species, including B. burgdorferi, B. americana, B. andersonii, and B. bissettiae/carolinensis-like strains. These results suggest that specific aspects of the DBS DNA extraction and PCR approach enabled the detection of Bartonella spp. and Borreliella spp. DNA from very small amounts of human whole blood from some patients, including specimens stored on filter paper for 17 years. Full article

Tick-borne illnesses (TBIs), especially those caused by Borrelia, are increasingly prevalent worldwide. These diseases progress through stages of initial localization, early spread, and late dissemination. The final stage often leads to post-treatment Lyme disease syndrome (PTLDS) or chronic Lyme disease (CLD), characterized by persistent and non-specific multisystem symptoms affecting multiple systems, lasting over six months after antibiotic therapy. PTLDS significantly reduces functional ability, with 82–96% of patients experiencing pain, including arthritis, arthralgia, and myalgia. Inflammatory markers like CRP and TNF-alpha indicate ongoing inflammation, but the link between chronic pain and other biomarkers is underexplored. This study examined the relationship between pain and biomarkers in TBI patients from an Irish hospital and their response to antibiotic treatment. Pain ratings significantly decreased after antibiotic treatment, with median pain scores dropping from 7 to 5 (U = 27215.50, p < 0.001). This suggests a persistent infection responsive to antibiotics. Age and gender did not influence pain ratings before and after treatment. The study found correlations between pain ratings and biomarkers such as transferrin, CD4%, platelets, and neutrophils. However, variations in these biomarkers did not significantly predict pain changes when considering biomarkers outside the study. These findings imply that included biomarkers do not directly predict pain changes, possibly indicating allostatic load in symptom variability among long-term TBI patients. The study emphasizes the need for appropriate antibiotic treatment for TBIs, highlighting human rights issues related to withholding pain relief. Full article