Search Results (389)

Lyme borreliosis (LB) is a tick-borne infection of global relevance that remains underrecognized, hindering effective surveillance and diagnosis. This lack of awareness and the limited specificity and low antibody titters of current serological assays underscore the need for improved diagnostic tools. Here, we investigated the molecular fine specificity of IgM antibody responses to five proteins of Borrelia burgdorferi. Materials and Methods: We employed peptide arrays on cellulose support (SPOT synthesis) to screen IgM epitopes and assess cross-reactivity through databank searches and Enzyme-Linked Immunosorbent Assay (ELISA). Validation was performed using ELISA and Receiver Operating Characteristic (ROC) curve analysis. Results: We identified ten IgM epitopes, of which four were classified as specific. The ELISA peptide assay demonstrated a sensitivity of ≥87.3%, specificity of ≥56.2%, and accuracy of ≥66.6%. A bi-specific peptide was subsequently synthesized and evaluated by ELISA using a panel of patient sera representing different pathologies. This result showed a sensitivity of 85.0% and a specificity of 100.0%, with significant differences in cross-reactivity between the leptospirosis and syphilis groups. Conclusions: These findings indicate that the identified peptide combinations could facilitate the development of new, highly specific serodiagnostic assays, thereby enhancing public health initiatives and epidemiological studies. Full article

Deer tick virus (DTV) is a Tick-Borne Orthoflavivirus endemic to the United States, transmitted to humans through bites from the deer tick, Ixodes scapularis, which is also the primary vector of Borrelia burgdorferi s.l., the causative agent of Lyme disease. Human infection with DTV can result in acute febrile illness followed by central nervous system complications, such as encephalitis and meningoencephalitis. Currently, there are mouse models established for investigating the pathogenesis and clinical outcomes of DTV that mimic human infections, but the strains of mice utilized are refractory to infection with B. burgdorferi s.l. Here, we describe the pathogenesis and clinical outcomes of DTV infection in C3H/HeJ mice. Neurological clinical signs, mortality, and weight loss were observed in all DTV-infected mice during the investigation. Infected animals demonstrated consistent viral infection in their organs. Additionally, neuropathology of brain sections indicated the presence of meningoencephalitis throughout the brain. This data, along with the clinical outcomes for the mice, indicates successful infection and showcases the neuroinvasive nature of the virus. This is the first study to identify C3H/HeJ mice as an appropriate model for DTV infection. As C3H/HeJ mice are already an established model for B. burgdorferi s.l. infection, this model could serve as an ideal system for investigating disease progression and pathogenesis of co-infections. Full article

As direct detection methods of Borrelia burgdorferi are limited, serology plays an important role in diagnosing Lyme disease (LD). There are various types of Lyme serological tests with varying diagnostic accuracy, so it is necessary to compare and rank them. The aim of this study is to compare the accuracy of various serological diagnostic methods for LD using network meta-analysis (NMA). We searched the Cochrane Library and PubMed databases for all serological diagnostic accuracy studies published from the discovery of LD until June 2024. After screening, we assessed the quality of the included studies with QUADAS-C and extracted relevant data. We calculated the Q* index of the receiver operating characteristic curve for each diagnostic test. Meta-disc 2.0 and Stata 15.0 were used to perform traditional meta-analysis and NMA with the gold standard (the comprehensive evaluation) as a reference. We then compared the Q* index values between different methods using two-by-two comparisons and ranked them accordingly. A total of 52 studies with 181,032 participants, including 5318 patients with LD, were included. These studies covered 14 diagnostic methods. The results of the NMA suggest that modified two-tiered testing (MTTT), C6 enzyme immunoassay (EIA), and standard two-tiered testing (STTT) rank in the top three among the 14 methods in terms of Q* index, with MTTT being the highest, followed by C6 EIA and STTT. MTTT and C6 EIA have higher overall diagnostic performance, and their accuracy is not inferior to that of the widely used STTT (PROSPERO CRD42022378326). Full article

The rise in multidrug-resistant bacterial strains and persistent infections such as Lyme disease caused by Borrelia burgdorferi highlights the need for novel antimicrobial agents. The present study explores the antioxidant, antibacterial, and cytotoxic properties of extracts from submerged mycelial biomass of Fomitopsis pinicola, cultivated in synthetic and lignocellulosic media. Four extracts were obtained using hot water and 80% ethanol. The provided analysis of extracts confirmed the presence of various bioactive compounds, including flavonoids, alkaloids, and polyphenols. All extracts showed dose-dependent antioxidant activity (IC₅₀: 1.9–6.7 mg/mL). Antibacterial tests revealed that Klebsiella pneumoniae was most sensitive, with the L2 extract producing the largest inhibition zone (15.33 ± 0.47 mm), while the strongest bactericidal effect was observed against Acinetobacter baumannii (MBC as low as 0.5 mg/mL for L1). Notably, all extracts significantly reduced the viability of stationary-phase B. burgdorferi cells, with L2 reducing viability to 42 ± 2% at 5 mg/mL, and decreased biofilm mass, especially with S2. Cytotoxicity assays showed minimal effects on NIH 3T3 cells, with slight toxicity in HEK 293 cells for S2 and L1. These results suggest that F. pinicola extracts, particularly ethanolic L2 and S2, may offer promising natural antimicrobial and antioxidant agents for managing resistant infections. Full article

Lyme disease has many different manifestations, including arthritis. There is no evidence that the pathogen Borrelia burgdorferi expresses toxins, so the presence of the organism is insufficient to cause inflammation and disease. Thus, the interaction between the causative pathogen and the many human immune system mechanisms responding to the organism is the apparent cause of inflammation and tissue damage/dysfunction. This review discusses many of the aspects of the relationship between organisms and host responses to summarize the many means by which the immune response can cause the synovitis of Lyme arthritis. Full article

Background/Objectives: Early diagnosis and oral or, in severe cases, intravenous antibiotics are usually effective for Lyme disease, but some patients have persistent symptoms unresponsive to standards of care, requiring alternative therapies. Disulfiram (DIS), a drug for alcoholism, is under investigation as a potential adjunctive treatment, but its low bioavailability, rapid metabolism, and safety concerns urge the development of improved formulations for clinical translation. Methods: Screening dissolution and permeation studies were investigated for vehicle and excipient selection, following the pharmacopeia perspectives to develop and optimize the low-dose DIS rectal suppository intended for application in post-treatment Lyme disease syndrome (PTLDS). Further characterizations were carried out by differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy. Results: Cyclodextrin (CD) encapsulation was investigated to improve the aqueous solubility of the hydrophobic drug. The dissolution of DIS from fatty base suppository was very slow; it was remarkably improved by the molecular encapsulation of the drug with CDs. The dissolution of DIS from a water-soluble base was more favorable, but incomplete. In the polyethylene glycol (PEG) based suppositories, the addition of CDs already in a physical mixture ensured the dissolution of the drug. The presented drug delivery system relates to a novel preparation for rectal administration comprising a low-dose disulfiram with improved solubility and permeability by the PEG and hydroxypropyl-β-cyclodextrin (HPBCD) synergistic matrix. Conclusions: The rectal dosage form containing the drug and CD in the physical mixture is advantageous, avoiding the hepatic first-pass effect, minimizing dose-limiting toxicity, simplifying production, and fasting the availability of the repositioned drug. Full article

Ticks carry a range of pathogens, the best known of which causes Lyme disease, prevalent in the northeastern United States. Emerging diseases do not yet consist of a wide range of Lyme diseases, raising the question of how long it takes for a newly introduced tick-borne disease to establish itself. The aim of this study was to address this question, with the agent of Lyme disease used as the test case. A prior process-based model of the Ixodes scapularis (Say 1821) life cycle and the transmission of Borrelia burgdorferi (Burgdorfer 1982) between this tick and its various hosts was used to predict the dynamics of disease introduction into a new area. The importance of temperature, infection probabilities, and tick host populations, relative to that of other factors, was established by a global sensitivity analysis using Latin hypercube sampling. The results of those samples were analyzed to determine the time to near-equilibrium. Eight locations in New Hampshire were chosen for high/low temperature, high/low mouse, and high/low deer values. Mammal abundance was estimated by relating the known mammal density from previous studies to a MaxEnt analysis output. The time required to reach Borrelia endemicity in the ticks of New Hampshire ranged from 8 to 20 years in regions where the tick population is viable, with a strong dependency on susceptible tick host populations. Full article

The Kaliningrad Oblast, located in the westernmost part of Russia and bordering European Union countries, is a popular tourist destination. However, limited research has been conducted on the bacteria found in ticks in this region. We, therefore, investigated the prevalence of certain bacteria, including Borrelia, Rickettsia, Anaplasma, and Ehrlichia, as well as the genospecies of the spotted fever group Rickettsia (SFGR) in Ixodes ricinus and Dermacentor reticulatus tick species. To accomplish this, we employed commercial qPCR for pathogen screening. We identified specific genospecies by sequencing the gltA and ompA gene fragments. In I. ricinus ticks, we found Borrelia burgdorferi sensu lato DNA in 35.6% of samples. We also found Rickettsia helvetica in 17.5% of ticks. Additionally, we detected Borrelia miyamotoi in 1.7% and Anaplasma phagocytophilum in 2.6%, while Ehrlichia chaffeensis/Ehrlichia muris were present in 0.6%. In D. reticulatus ticks, we detected only Rickettsia conorii subsp. raoultii DNA, with a prevalence of 6.1%. These findings demonstrate a substantial risk of Lyme disease and other tick-borne infections from early spring through late autumn, emphasizing the importance of ongoing monitoring for these pathogens in the region. Full article

Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (s.l.) and babesiosis, caused by Babesia divergens and Babesia venatorum, are both transmitted by the ixodid tick Ixodes ricinus. Although these diseases coexist in Spain and other European regions, no studies have been carried out to assess the impact on the health of patients exposed to both causative pathogens. This retrospective study, conducted in Asturias in northwestern Spain between 2015 and 2017, analyzed the possible complications arising from exposure to these pathogens. To this end, the epidemiological, clinical and analytical features of two groups of a cohort of 120 LB patients exposed to one or two of the pathogens were compared. The cohort comprised 73 patients who had only been infected with Bo. burgdorferi s.l. (Bb group) and 47 patients who were seropositive for Ba. divergens/venatorum in addition to being infected with Bo. burgdorferi s.l. (BbBdv group). The results showed that LB patients who had also been exposed to infection with Babesia spp. (BbBdv group) had significantly more cardiorespiratory symptoms, in particular dyspnea and first- and second-degree atrioventricular (AV) blocks, compared to those who had been infected with Bo. burgdorferi s.l. alone (Bb group). No relevant differences in other symptoms, epidemiological factors or analytical tests were observed between the two groups. Full article

Hard ticks are vectors of a wide range of pathogens, with tick-borne bacteria being among the most frequently detected. This study presents a first approach to the identification of human-biting ticks in the Basque Country (northern Iberian Peninsula), where previous research has mainly focused on ticks from vegetation and domestic and wild animals. The aim of this study was (i) to identify tick species collected in hospitals and health centres and (ii) to determine the presence and identify of pathogenic bacteria that they may carry using PCR, RLB and sequencing methods. A total of 181 ticks were collected and grouped in pools of one, two or three specimens, resulting in 157 samples. Morphological and molecular identification of collected ticks revealed that most specimens belonged to Ixodes ricinus (88.5%). Additionally, Rhipicephalus bursa, Haemaphysalis punctata, Dermacentor reticulatus and Dermacentor marginatus were also identified. A total of 25 samples (15.9%) tested positive for DNA from the targeted pathogens. The most prevalent vector-borne bacteria were Borrelia spp. (6.4%), followed by Rickettsia spp. (5.1%), Anaplasma phagocytophilum (2.5%) and Coxiella spp. (1.9%). Species identified included B. afzelii, B. garinii, B. miyamotoi, B. valaisiana, B. burgdorferi s. s., R. monacensis, “Candidatus R. rioja”, R. helvetica and R. massiliae. This study highlights the usefulness of combining molecular diagnostics with passive surveillance of human-attached ticks as an effective tool for regional monitoring of ticks and tick-borne pathogens. Full article

Vector-borne diseases (VBDs) significantly impact global child health, with mosquito-transmitted infections like malaria and arboviruses accounting for a substantial portion of this burden. However, other arthropod-borne diseases—transmitted by vectors such as ticks, fleas, sand flies, lice, and triatomine bugs—also pose serious health risks to children worldwide. This review specifically excludes mosquito-borne diseases to concentrate on these less-discussed yet clinically important pediatric VBDs. We examine their clinical manifestations, diagnostic challenges, and treatment options, highlighting the unique vulnerabilities of children, including immature immune systems, behavioral factors, and communication barriers that can delay diagnosis. Additionally, we explore how environmental and anthropogenic factors, such as climate change and urbanization, are expanding the geographic range of these vectors, leading to the emergence of diseases like Lyme disease and leishmaniasis in new regions. By focusing on non-mosquito VBDs, this review aims to raise awareness and inform healthcare providers and public health practitioners about the comprehensive landscape of pediatric vector-borne diseases. Full article

Ticks carry numerous pathogens that, if transmitted, can cause disease in humans and animals. Research on pathogens transmitted from ticks to humans is essential for improving public health strategies against tick-borne diseases (TBDs). In this study, Ixodes ricinus ticks found on humans were collected and examined between 2019 and 2024. This study is about the molecular characteristics of tick-borne pathogens (TBPs) in the region of northern Serbia, including Borrelia burgdorferi sensu lato (s.l.), Anaplasma phagocytophilum, and Coxiella burnetii. We identified B. burgdorferi s.l. as the most prevalent in ticks (20.45%). Molecular analysis identified two genospecies, B. afzelii and B. burgdorferi s.s., indicating genetic diversity among Borrelia spirochetes. A. phagocytophilum was detected in ticks with a prevalence of (1.62%), while C. burnetii was not found in any of the ticks. Our findings highlight the necessity of monitoring tick pathogens in ticks removed from humans. Serbia is an endemic region for some tick-borne diseases, such as Lyme disease. Regular surveillance of tick populations, with molecular identification of pathogens, offers insight into transmission dynamics, allowing for monitoring and public health interventions to be created if needed due to increased risk. 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

Babesiosis is an emerging tick-borne illness, and pulmonary manifestations have not been well described previously. This is a single-center, retrospective study of hospitalized adults with confirmed babesiosis at Westchester Medical Center (Valhalla, NY, USA) from 2006 to 2023. Descriptive analysis was used to summarize the demographic and clinical data. Logistic regression was used to determine factors associated with severe disease and mortality. A total of 147 cases were reviewed; 63 were severe, 41 were admitted to the intensive care unit, and ten died. Respiratory symptoms were observed in 42% of cases (cough, dyspnea, oxygen supplementation, respiratory failure). A total of 55 patients had an abnormal chest radiograph (infiltrates, pleural effusions), and 75% of severe cases had parasitemia ≥ 10%. Factors associated with severe cases included age ≥ 70 years, severe dyspnea, radiographic abnormalities, white blood cell count > 5000 cells/dL, hemoglobin 8 g/dL or less, and increased creatinine. Lyme seropositivity was common (28%). Exchange transfusion did not correlate with outcome. Increased mortality was more likely in patients 70 years or older or in those having any of the following: encephalopathy, acute kidney injury, severe dyspnea on admission, abnormal chest radiograph, and requiring intubation. In conclusion, pulmonary symptoms including abnormal chest radiograph are not uncommon in babesiosis and are associated with worse outcomes. Full article