Search Results (31)

Background/Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) describes the rapid onset of obsessive–compulsive symptoms or severe food restriction, accompanied by neuropsychiatric or somatic features that are not better explained by another disorder. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) is a related, more narrowly defined construct in which symptoms are temporally associated with group A Streptococcus infection. This review examines clinical symptoms, infectious associations, proposed immune mechanisms, biomarker limitations, and treatment strategies for infection-associated PANS/PANDAS. Methods: A structured narrative search of PubMed/MEDLINE, Embase, the Cochrane Library, Google Scholar/publisher-indexed literature, ClinicalTrials.gov, and reference lists was performed up to 16 June 2026. Original cohorts, case series, systematic reviews, narrative reviews, consensus guidance, mechanistic studies, and registered prospective studies were prioritized. The review was not designed as a PRISMA-ScR scoping review; however, the methods were expanded to improve transparency and align with SANRA principles. Results: Group A Streptococcus remains the best characterized infectious association, although prospective studies have not uniformly demonstrated a consistent temporal relationship between streptococcal infection and neuropsychiatric exacerbations. Parent-reported surveys and case-based literature also describe temporal associations with Mycoplasma pneumoniae, influenza-like illnesses, upper respiratory infections, Borrelia burgdorferi, Epstein–Barr virus, and SARS-CoV-2. Proposed mechanisms include molecular mimicry, anti-D1R and anti-D2R antibodies, other antineuronal antibodies, calcium/calmodulin-dependent protein kinase II signaling, blood–brain barrier vulnerability, cytokine and Th17 effects, neuroinflammatory amplification, basal ganglia/CSTC circuit dysfunction, and gut–oral–brain immune interactions. None currently provides a definitive diagnostic biomarker. Conclusions: Infection-associated PANS is best approached as a clinically defined, heterogeneous neuroimmune presentation that requires rigorous differential diagnosis, multidisciplinary care, cautious treatment escalation, prospective biomarker validation, and large, multicenter treatment trials. Full article

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

Objectives: Borrelia burgdorferi sensu lato, a spirochete bacterium responsible for Lyme borreliosis—the most common tick-borne infection in North America and Europe—can trigger the production of antiphospholipid antibodies. These antibodies target host lipids such as cardiolipin (CL), phosphatidic acid (PA), phosphatidylcholine (PC), and phosphatidylserine (PS), which the spirochete incorporates into its membrane from the surrounding environment. Although antiphospholipid antibodies are typically associated with antiphospholipid syndrome (APS), they may also arise during infections, including Lyme borreliosis. This study aimed to develop and optimize several enzyme-linked immunosorbent assays (ELISAs) for measuring various antiphospholipid antibodies in patients with Lyme borreliosis. Methods: Thirty patients diagnosed with Lyme borreliosis were enrolled: ten with solitary erythema migrans (EM), ten with multiple EM (MEM), and ten with late manifestations known as acrodermatitis chronica atrophicans (ACA). Forty healthy blood donors served as controls. Four distinct antiphospholipid antibody ELISAs were developed, each using a different phospholipid coating: CL, PA, PC, and PS. Serum of APS patient was used as a positive control and for standard curve generation. Results: All four ELISAs were successfully established and demonstrated good measurement precision. Significant differences in antiphospholipid antibody levels and positivity rates were observed between Lyme borreliosis patients and healthy blood donors. Notably, levels of antibodies directed against PA (aPA), PC (aPC), and PS (aPS), both IgG and IgM, were significantly higher in patients with late Lyme borreliosis, manifested as ACA, compared to healthy blood donors. In contrast, anti-CL (aCL) levels did not differ significantly between groups. Patients with ACA also showed the highest frequency of multiple antiphospholipid antibody positivity, with 7 out of 10 patients testing positive for three or more antiphospholipid antibodies. Conclusions: Accurate and precise in-house ELISAs for the detection of aCL, aPA, aPC, and aPS using APS sera as standard material were developed and validated for the analysis of samples of patients with Lyme borreliosis. Our data suggest that antiphospholipid antibody levels—specifically aPA, aPC, and aPS—differ across clinical manifestations of Lyme borreliosis, with the greatest increases observed in patients with ACA. Full article

Background: Borrelia miyamotoi is an emerging tick-borne pathogen causing relapsing fever in humans. Although Saint Petersburg and the surrounding Leningrad Oblast harbor a high abundance of ixodid ticks (I. ricinus, I. persulcatus), no integrated assessment has yet simultaneously addressed pathogen circulation in vectors, reservoir hosts, and human populations in this specific northwestern region of Russia. Methods: During 2022–2024, we collected 1518 questing adult ticks and trapped 516 small mammals in Saint Petersburg and Leningrad Oblast. B. miyamotoi DNA was detected by real-time PCR. Sera from 3743 randomly selected volunteers (1553 from Saint Petersburg, 2190 from Leningrad Oblast) were tested for anti-B. miyamotoi IgG/IgM using a protein microarray (antigens: GlpQ, Vmps, flagellin). Infection rates and seroprevalence with 95% Wilson confidence intervals were compared using chi-square tests. Results: The overall tick infection rate was 3.78% (57/1506). I. ricinus had a significantly higher prevalence (4.94%; 95% CI: 3.67–6.60%) than I. persulcatus (2.29%; 95% CI: 1.39–3.74%; p = 0.011). Ticks from Leningrad Oblast also showed markedly elevated infection rates (4.98%; 95% CI: 3.75–6.58%) compared to those from Saint Petersburg (1.89%; 95% CI: 1.06–3.35%; p = 0.004). Small mammals exhibited substantially higher infection rates in Leningrad Oblast (39.44%; 95% CI: 31.78–47.65%) than in Saint Petersburg (13.90%; 95% CI: 10.76–17.78%; p < 0.001). Bank voles (Myodes glareolus) and yellow-necked mice (Apodemus flavicollis) were the main reservoirs; synanthropic rodents trapped within the city were found to be infected for the first time. No significant organotropism was detected, but positive correlations between infection in the heart, liver, and kidney suggested hematogenous dissemination. The overall human seroprevalence of B. miyamotoi was 1.71% (95% CI: 1.34–2.18%) and was significantly higher in Leningrad Oblast (2.19%; 95% CI: 1.66–2.89%) than in Saint Petersburg (1.03%; 95% CI: 0.64–1.67%; p = 0.010). In contrast, the seroprevalence of B. burgdorferi s. l. did not differ between the two regions (approximately 5.1%). Conclusions: This first comprehensive, multi-level investigation in Saint Petersburg and Leningrad Oblast reveals a stable epidemiological gradient: natural foci in Leningrad Oblast sustain higher B. miyamotoi circulation in ticks and rodents, which translates into a two-fold higher exposure of the rural population. The findings highlight the need to include B. miyamotoi in regional tick-borne infection surveillance programs and to adopt differentiated risk assessment strategies for urban and rural settings. Full article

Borrelia burgdorferi sensu lato is a complex of spirochetes that includes the main pathogenic species B. burgdorferi sensu stricto, B. afzelii, and B. garinii, the causative agents of Lyme disease. Our aim was to determine the seroprevalence of anti-Borrelia IgG antibodies and assess associated risk factors among blood donors from Western Romania. We conducted a cross-sectional study of 1347 consecutive donors at the Regional Blood Transfusion Center in Timisoara, Western Romania, between November and December 2018. Participants completed an epidemiological questionnaire and serum samples were tested for IgG antibodies against B. burgdorferi sensu lato using the VIDAS^® Lyme IgG assay. The overall seroprevalence was 2.08% (28/1347). Individuals aged 46–55 years had the highest prevalence (3.79%) and a more than fivefold increased risk compared to those aged 18–25 years (aOR = 4.77; 95% CI: 1.24–18.27; p = 0.023). Soil exposure was also independently associated with higher seropositivity (aOR = 2.37; 95% CI: 1.10–5.09; p = 0.027). Other factors, including residence, gender, and pet ownership, showed no significant associations. Our findings provide new epidemiological data for Romania and emphasize the importance of environmental exposures in shaping Borrelia seroprevalence. Full article

Ehrlichiosis and anaplasmosis are endemic to tropical and subtropical regions and pose significant zoonotic threats to both human and animal health. This study aimed to detect anti-Ehrlichia canis, anti-Borrelia burgdorferi, and anti-Anaplasma antibodies in dogs from the rural–urban area of Huamanga, Ayacucho. The cross-sectional survey was conducted at the Facultad de Ciencias Biológicas of the Universidad Nacional de San Cristóbal de Huamanga between May and August 2023. Samples were collected via venipuncture, and antibody detection was performed using the immunochromatographic assay Anigen Rapid CaniV-4 kit. Frequencies, percentages, and statistical analyses were conducted using the SPSS^® software package. A total of 107 samples from dogs in the Covadonga Human Settlement were analyzed, comprising 64 (59.8%) males and 43 (40.2%) females. The majority (78.5%) were from mixed-breed dogs, while other dogs breed included Schnauzers, Pekingese, and Pitbulls. Thirty positive samples were identified, with antibodies against Ehrlichia canis (15.9%), Anaplasma phagocytophilum/Anaplasma platys (3.7%), mixed infections of Ehrlichia canis and Anaplasma phagocytophilum/Anaplasma platys (6.5%), and Ehrlichia canis/Borrelia burgdorferi (1.9%) detected, as well as an association between vector exposure and the presence of Ehrlichia canis antibodies. These findings underscore the urgent need for the implementation of integrated control strategies and enhanced surveillance programs targeting tick-borne diseases in high-risk areas, along with targeted educational campaigns to promote responsible pet ownership and preventive measures. Full article

Argasid ticks Ornithodoros erraticus and Ornithodoros moubata are major vectors of zoonotic pathogens, including the African swine fever virus and relapsing fever Borrelia spp., and their control is essential to reduce disease transmission. In this study, we evaluated the immunogenicity and protective efficacy of four Ornithodoros tick antigens formulated as mRNA–lipid nanoparticles (mRNA-LNPs): OeSOD, OeTSP1, OmPLA2, and Om86. Rabbits were immunised with three doses of each mRNA-LNP construct, and immune responses and tick biological parameters were assessed following infestation with both tick species. All mRNA-LNP constructs induced antigen-specific IgG responses that recognised native proteins in tick saliva and midgut extracts. Vaccination resulted in significant reductions in female oviposition and fertility, which correlated with antibody levels, and yielded protective efficacies of 21.9–41.6% against O. moubata and 23.1–41.6% against O. erraticus. Notably, the mRNA-LNPs of OeSOD and OeTSP1 outperformed their recombinant counterparts against O. moubata, and Om86 mRNA-LNP conferred markedly improved protection against both O. moubata and O. erraticus. These findings highlight the potential of mRNA-LNP vaccines to induce effective anti-argasid tick immunity and provide a promising platform for the development of sustainable strategies to control argasid ticks and associated pathogens. Full article

Several diseases caused by tick-borne pathogens, including Lyme borreliosis (LB) and spotted fever group rickettsioses, are endemic in the Balkan Peninsula, positioned between Central Europe and the Middle East. This cross-sectional study aimed to assess serological exposure to Borrelia spp. and spotted fever group Rickettsiae (SFGR) among individuals with recent tick bites and healthy controls in two Balkan countries—Serbia and North Macedonia. Serum samples from 223 participants were tested for anti-Borrelia and anti-SFGR IgG antibodies. SFGR exposure was significantly higher in tick-exposed individuals from Skopje (North Macedonia) compared to those from Novi Sad (Serbia) (30.9% vs. 8.0%; p = 0.003). In contrast, anti-Borrelia IgG was more frequently detected in Novi Sad, though differences did not reach statistical significance. The findings support a north-to-south gradient in Borrelia exposure and a reverse trend for SFGR, consistent with earlier studies and regional tick infection data. Given the high SFGR exposure and limited clinical reporting in North Macedonia, the results highlight the likelihood that tick-borne rickettsioses remain under-recognized. Additionally, Borrelia exposure in North Macedonia warrants further investigation. These findings emphasize the need for enhanced tick-borne disease surveillance, identification of endemic zones, and improved diagnostic and public health infrastructure in both countries. Full article

Lyme disease (LD), caused by infection with the tick-borne bacteria, Borrelia burgdorferi, is associated with a wide array of symptoms in human patients. Variations in clinical manifestations are thought to be influenced by genetic differences among B. burgdorferi strains. In this study, we evaluated the infectivity, tissue bacterial load, pathology, and immunogenicity of five strains of B. burgdorferi sensu stricto (297 Ah130, Bb16-54, B31-A3, Bb16-126, JD1) in female C3H/HeN mice at three infectious doses (10⁴, 10⁵, 10⁶ spirochetes). We found that strains Bb16-126 and JD1 were the most infectious, resulting in 100% infection across all the tested doses. Strain Bb16-126 caused the highest bacterial burden in the heart tissue and significant carditis, whereas JD1 exhibited the lowest spirochete load in the heart and minimal carditis. In comparison, strain B31-A3 demonstrated the highest abundance in the tibiotarsal joint. Infection with all the strains induced severe lymph node hyperplasia, with JD1 producing the greatest increase in cellularity. Using a diagnostic C6 peptide ELISA, all the strains induced significant anti-C6 IgM and IgG antibody titers at 14 days post-infection; however, strain B31-A3 elicited the highest anti-C6 IgM titers. Our findings demonstrate the importance of strain diversity in shaping B. burgdorferi pathogenesis in a mouse model and provide insights for developing strain-specific diagnostic, therapeutic, and vaccine strategies. Full article

The epidemiological situation related to infectious diseases is influenced by many factors. To monitor actual trends in selected zoonoses, a total of 473 serum samples from farmers, forestry workers, and veterinarians were collected for serological examination. Anti-Borrelia burgdorferi sensu lato (s.l.) antibodies were tested with ELISA and Western blot (WB) tests; the detection of anti-Toxoplasma gondii antibodies was performed using an enzyme linked fluorescence assay (ELFA). Antibodies to bartonellosis, anaplasmosis, and chlamydiosis were determined by indirect immunofluorescent test (IFA), whereas antibodies to yersiniosis and mycoplasmosis were confirmed in the ELISA test. Positive or borderline results of antibodies against B. burgdorferi s.l. in the ELISA test were detected in 33.8% of the study population. The borderline or positive ELISA test results for at least one antibody class were confirmed by WB in 58.7% of cases. The IgG antibodies against Anaplasma phagocytophilum, Toxoplasma gondii, and Mycoplasma pneumoniae were detected in 9.6%, 51.7%, and 63.6% of samples, respectively. Antibodies against Yersinia spp., Bartonella henselae, and Chlamydia pneumoniae were found to vary between 43 and 47%. Full article

Lyme borreliosis (LB) and tick-borne encephalitis (TBE) are important tick-borne diseases in Europe. This study aimed to investigate the seroreactivity against Borrelia burgdorferi and TBE virus (TBEV) in tick-infested individuals in North Macedonia and Serbia. Serum samples were collected from tick-infested individuals and from healthy individuals in the same regions. Samples were tested for anti-Borrelia IgG reactivity and TBEV-neutralizing antibodies. Results showed higher seroreactivity against Borrelia antigens in patients and healthy donors from Novi Sad compared to those from the Skopje region. However, there was no statistically significant difference between tick-infested patients and healthy donors within each region. No TBEV-neutralizing antibodies were detected in participants from Novi Sad or in the control groups, except for one person from North Macedonia who had a moderate TBEV-neutralizing reaction. The study highlights the need for improved surveillance and diagnostic capabilities for LB and TBE in these regions. It also suggests the potential existence of TBEV foci in North Macedonia. The findings provide a complementary understanding of the LB and TBE epidemiology in the studied regions; however, further research is needed to investigate the presence and distribution of Borrelia spp. and TBEV in ticks to assess the significance of detected seroreactivity. Full article

Lyme disease, caused by some strains of bacterial spirochetes Borrelia burgdorferi sensu lato (Bbsl), affects humans but also domestic animals including horses. The primary pathogens in horses in Europe are B. afzelii, B. garinii and B. burgdorferi sensu stricto. To our knowledge, there are no data available on the seropositivity of B. burgdorferi s.l. in horses from the Czech Republic. In this country, horses are mainly used for sport, breeding, and recreational riding in areas where vectors of B. burgdorferi s.l. are present, which is why they are frequently at risk of infection. The aim of the study was to detect anti-borrelia IgM and IgG antibodies in clinically healthy and sick horses from the Czech Republic and to evaluate the risk factors of infection. In total, sera of 262 horses (247 clinically healthy horses and 15 horses hospitalized due to symptoms of encephalitis/meningoencephalitis) were examined by an indirect sandwich enzyme-linked immunosorbent assay. Positivity of B. burgdorferi was 27% (66/247) in clinically healthy horses (21% IgM, 7% IgG and 3% IgM + IgG antibodies) and 20% (3/15) in horses with clinical signs (20% IgM, 7% IgG and 7% IgM + IgG). In the clinically healthy horses, positivity statistically differed (p ≤ 0.05) only in Pony and Warmblood breeds, being the most affected at 32% and 30%, respectively, while other characteristics (sex, age, usage and localities) had no effect on positivity. This is the first survey of antibodies to B. burgdorferi s.l. in Czech horses showing that horses are exposed to ticks infected with B. burgdorferi s.l. This should be taken into account when making differential diagnoses in patients with non-specific symptoms to start with adequate therapy. Full article

There is little known about the dynamics within responses to Borrelia spp. upon repeated exposure to tick bites and the development of serological markers over time. Most studies have investigated antibody development in risk populations over a short period of time. Therefore, we aimed to study the dynamics of anti-Borrelia antibodies in forestry service workers over 8 years in association with tick bite exposure. Methods: Blood samples from 106 forestry service workers originally included in the 200 Functional Genomics Project (Radboudumc, Nijmegen, the Netherlands) were followed for 8 years and tested annually for anti-Borrelia antibodies (ELISA and Western blot). IgG seroconversion was related to the number of tick bites in the previous year, which was obtained through annual questionnaires. The hazard ratio for Borrelia IgG seroconversion was calculated using Cox regression survival analysis and a logistic regression model, both adjusting for age, gender and smoking. Results: Borrelia IgG seropositivity in the study population did not vary significantly between years and the average prevalence was 13.4%. Of the 27 subjects that underwent seroconversion during the study period, 22 reconverted from positive to negative. Eleven subjects seroconverted a second time. The total seroconversion rate per year (negative to positive) was 4.5%. Active smoking was associated with IgG seroconversion in the >5 tick bites group (p < 0.05). According to the two models used, the risks of IgG seroconversion in the >5 tick bites group were HR = 2.93 (p = 0.10) and OR = 3.36 (p < 0.0005). Conclusions: Borrelia IgG seroconversion in forestry service workers was significantly related to increasing tick bite exposure in a survival and logistic regression model adjusting for age, gender and smoking. Full article

The aim of this study was to perform a detailed epidemiological overview of Lyme neuroborreliosis (LNB) 2008–2021 in a highly Lyme borreliosis-endemic area in Sweden using a geographic information system (GIS). Diagnosis of LNB was based on clinical symptoms and analysis of cerebrospinal fluid (CSF) according to European guidelines. From laboratory databases and medical records, we detected all patients with CSF pleocytosis and intrathecal anti-Borrelia antibody production and listed clinical features. The distribution of LNB cases within Kalmar County, Sweden was investigated using GIS. In total, 272 cases of definite LNB were confirmed with an average yearly incidence of 7.8/100,000. Significant differences in incidence were noted between children 0–17 years (16/100,000) and adults 18+ years (5.8/100,000) (p < 0.001), between rural (16/100,000) and urban areas (5.8/100,000) (p < 0.001) and between selected municipalities (p < 0.001). Distinct clinical differences in presentation of LNB were also noted between children and adults. Thus, the incidence of LNB varies significantly locally and in relation to age, and clinical presentation shows differences between children and adults. Surveillance of LNB and knowledge of local epidemiological conditions may facilitate preventive measures. Full article