Common Tick-borne Disease Research Articles

Estimated incidence of symptomatic Lyme borreliosis cases in five southern coastal counties in Norway, 2022.

Lyme borreliosis (LB), the most common tick-borne disease in Europe, is endemic to southern coastal Norway. LB commonly presents as erythema migrans, which can disseminate, resulting in more severe disease such as Lyme neuroborreliosis or arthritis. In Norway, public health LB surveillance is conducted via mandatory reporting of laboratory-confirmed disseminated cases. From 2012 to 2022, Norway's surveillance-reported incidence of laboratory-confirmed disseminated LB increased by 78%. Although surveillance provides estimates of the incidence of disseminated LB, this study sought to estimate the incidence of symptomatic LB to better understand Norway's LB disease burden. Two studies were identified that, when combined, estimated an LB seroprevalence of 6.8% in the general adult population in southern Norway. Utilizing data from these seroprevalence studies, public health surveillance, and results from literature searches indicating that 37% of seroconverted LB cases are symptomatic and that the duration of LB antibody detection ranges from 10 to 20 years, we estimated that there were 315-630 symptomatic LB cases per 100,000 adult population in five southern coastal counties in Norway in 2022 and 24-48 cases of symptomatic LB for every public health surveillance-reported LB case in adults in these five counties in Norway.

Development of novel multi-protein chimeric immunogens that protect against infection with the Lyme disease agent, Borreliella burgdorferi.

Lyme disease is the most common tick-borne disease in North America. A vaccine for use in humans is not available. Here, we detail the development of two chimeric vaccine antigens, BAF and Chv2M. BAF elicits Abs that target proteins and protein variants produced by Borreliella species in ticks (OspB and OspA) and mammals (FtlA/B). OspB serves as the backbone structure for the BAF chimeric. Two OspA221-240 epitope-containing domain (ECD) variants (#A1 and #A15) were inserted into a loop in OspB. The N-terminal region of the FtlA protein was joined to the C-terminus of the chimeric. The second chimeric, Chv2M, consists of L5 (loop 5) and H5 (helix 5) ECDs derived from diverse OspC proteins. Borreliella species produce OspC upon exposure to the bloodmeal and during early infection in mammals. Here, we demonstrate that BAF and Chv2M are potent immunogens that elicit Abs that bind to each component protein (FtlA, FtlB, OspB, and multiple OspA and OspC variants). Anti-BAF and anti-Chv2M Abs kill Borreliella burgdorferi strains through Ab-mediated complement-dependent and complement-independent mechanisms. Eighty percent (32/40) of mice that received a three-dose vaccine regimen were protected from infection with B. burgdorferi B31. Efficacy increased to 90% (18/20) when the amount of Chv2M was increased in the third vaccine dose. Readouts for infection were flaB PCR and seroconversion to VlsE. This study establishes proof of principle for a chimeric immunogen vaccine formulation that elicits Abs to multiple targets on the B. burgdorferi cell surface produced during tick and mammalian stages of the enzootic cycle.IMPORTANCELyme disease is a growing public health threat across parts of the Northern Hemisphere. Regions that can support sustained tick populations are expanding, and the incidence of tick-borne diseases is increasing. In light of the increasing risk of Lyme disease, effective preventive strategies are needed. Most vaccine development efforts have focused on outer surface protein A, a Borreliella burgdorferi protein produced only in ticks. Herein, we describe the development of a novel vaccine formulation consisting of two multivalent chimeric proteins that are immunogenic and elicit antibodies with bactericidal activity that target several cell surface proteins produced by the Lyme disease spirochetes in feeding ticks and mammals. In a broader sense, this study advances efforts to develop custom-designed vaccinogens comprised of epitope-containing domains from multiple proteins.

Knowledge, attitudes and behaviour towards ticks and tick-borne diseases—A survey among Lyme borreliosis cases in Bavaria in 2019

Lyme borreliosis (LB) is the most common tick-borne disease (TBD) in Germany. In Bavaria, the average annual incidence of reported cases was 34.3 cases per 100,000 inhabitants between 2013 and 2020, although case numbers were presumed to be substantially higher. Since no vaccine against LB is currently available, prevention focuses on individual protection measures. This study aims to address knowledge, attitudes, and behaviours among LB cases, a population group at increased exposure to ticks, tick bites and repeated infections.We invited Bavarian LB cases reported between weeks 23 and 35 in 2019 to participate in a questionnaire study. Questions included socio-demographic characteristics, experiences with TBDs, potential tick exposures, details of the recent episode of LB, and knowledge, attitudes, and behaviours regarding TBDs and protection measures.Among the 377 participants, 300 were adults/adolescents, 77 were children (<14 years). Two third resided in rural areas. Although mostly well informed, a significant proportion of participants did not know or were misinformed about availability of repellents (48.5 %), risk of LB in their district (24.9 %), ticks not falling from trees (22.1 %) and non-availability of vaccination against LB (20.9 %). Even though a majority perceived checking for ticks after spending time outdoors, wearing long clothes, wearing closed shoes and tucking pants in socks as effective protection measures against tick bites, a much lower proportion applied those measures frequently (proportions perceived vs. applied: 99.2 % vs. 72.1%; 93.8 % vs. 40.2 %, 88.8 % vs. 51.1 % and 85.4 % vs. 16.8 %, respectively).Identified lack of knowledge or misconception regarding risk factors, availability of protection measures and tick behaviour may hamper application of recommended protection measures. There appeared to be a discrepancy between perceived effectiveness and frequency of application of protection measures. Addressing identified gaps in education campaigns, specifically targeting people living in rural areas, and utilising physician-patient interactions for education are promising entry points to increase awareness and prevent TBDs. Moreover, motivators and barriers for the application of preventive behaviour should be subject of future studies.

The impact of Lyme disease on quality of life and multiorgan function, diagnosis, late stages of the disease and PTLDS

Introduction and purpose of the work: Lyme disease is the most common tick-borne disease in the world. It is caused by bacteria of the Borrelia genus. It is transmitted by ticks of the Ixodes genus. The disease caused by these bacteria can affect many organs of the human body. Knowledge about diagnosis, form of the disease and treatment is necessary because this disease entity can often be encountered in clinical practice. The aim of the study is to present information on available diagnostic methods and to describe the organ form of the disease, distinguishing: articular form, cardiac form and neuroborreliosis, based on a review of the current literature. Review methods: The review is based on 20 articles obtained from PubMed databases, using the keywords: "Lyme joint disease", "neuroborrelia", "Lyme heart disease". Published between 2000 and 2023. Brief description of the state of knowledge: Lyme disease most often causes symptoms affecting the skin, musculoskeletal system, heart muscle, and nervous system. The diagnosis of the disease is based on the clinical symptoms presented by the patient. The key symptom of the disease is the presence of erythema migrans (EM). The articular form of Lyme disease is characterized by an ongoing inflammatory process located within the joint. It is located within large ponds. The most common cardiac form of the disease is self-limiting cardiac inflammation caused by Lyme disease. However, in the course of neuroborreliosis, meningitis is observed. Treatment is based on antibiotic therapy. Conclusions: Lyme disease is a life-threatening disease. It can cause non-specific symptoms, so it is important to diagnose it as early as possible and treat it to prevent progression.

Incidence of symptomatic Borrelia burgdorferi sensu lato infection in Romania, 2018−2023

BackgroundLyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. Although public health surveillance for LB has been conducted in Romania since 2007, the extent of under-detection of Bbsl infections by LB surveillance has not been estimated. We therefore estimated the under-detection of symptomatic Bbsl infections by LB surveillance to better understand the LB burden in Romania.MethodsThe number of incident symptomatic Bbsl infections were estimated from a seroprevalence study conducted in six counties (population 2.3 M) and estimates of the symptomatic proportion and duration of persistence of anti-Bbsl immunoglobulin G (IgG) antibodies. The number of incident symptomatic Bbsl infections were compared with the number of surveillance-reported LB cases to derive an under-detection multiplier, and then the under-detection multiplier was applied to LB surveillance data to estimate the incidence of symptomatic Bbsl infection from 2018 to 2023.ResultsWe estimate that there were 1968 individuals with incident symptomatic Bbsl infection in the six counties where the seroprevalence study was conducted in 2020, compared with the 187 surveillance-reported LB cases, resulting in an under-detection multiplier of 10.5 (i.e., for every surveillance-reported LB case, there were 10.5 symptomatic incident Bbsl infections). The incidence of symptomatic Bbsl infection in the six counties was 86.9/100,000 population in 2023, similar to the incidence in 2018−2020 (86.0) and higher than in 2021−2022 (40.3).ConclusionsThere is a higher incidence of symptomatic Bbsl infection than is reported through public health surveillance for LB in Romania. Additional efforts are needed to strengthen disease prevention and address the important public health problem of LB.Graphic

Serological Assessment of Lyme borreliosis in Bulgaria: A Nationwide Study.

Lyme borreliosis (LB), a tick-borne infection caused by bacteria in the Borrelia burgdorferi sensu lato complex, is increasingly prevalent on the Balkan Peninsula, including Bulgaria, where it is the most common tick-borne disease. This study aimed to assess the seroprevalence of LB across Bulgaria by analyzing 1892 serum samples for specific IgG antibodies using a two-tier testing protocol involving an ELISA and immunoblot methods. The results revealed an overall seroprevalence rate of 5.4%, with significant variation based on age, sex, and residence. Seroprevalence increased with age, peaking at 8.4% in individuals over 65 years. Males had a seroprevalence of 8.4% compared to 3.3% in females, and rural residents showed higher seroprevalence (10.2%) compared to urban residents (4.4%). Regional analysis indicated that seroprevalence ranged from 0.0% to 20.0%, with higher rates in northern provinces such as Gabrovo (18.9%) and Targovishte (20.0%). This study highlights the importance of two-step testing protocols for accurate diagnosis and underscores the need for increased awareness and further research to enhance public health measures and the management of LB in Bulgaria.

Clinical and etiological characteristics of severe hemorrhagic fever caused by coinfection of hantaan orthohantavirus and severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS) usually have different infection routes, and coinfection is relatively rare. This study examines the clinical and etiological characteristics of coinfection by these two pathogens to provide important references for clinical diagnosis and treatment. Blood samples from 22 clinically diagnosed patients with HFRS were collected for molecular detection of HFRS and common tick and mouse borne diseases. Inoculate the blood of six severe and critically patients into cells to isolate and proliferate potential viruses, and retest the cell culture to determine the pathogen. In addition, complete data were collected from these 22 HFRS and concurrent SFTS patients, and white blood cells (WBCs), platelet (PLT), blood urea nitrogen (BUN), creatinine (Cr) and other data were compared and analyzed. A total of 31 febrile patients, including 22 HFRS patients and 9 SFTS patients, were collected from September 2021 to October 2022. Among these HFRS patients, 11 were severe or critical. Severe and critical HFRS patients were characterized by rodent exposure history, pharyngeal and conjunctival hyperemia, abnormal WBC and PLT counts, and elevated BUN and Cr values. Virus isolation and molecular detection on blood samples from 6 patients showed that three of the six severe patients were positive for hantaan virus (HTNV), and two of the three HTNV positives were also positive for SFTS bunyavirus (SFTSV). The two coinfected patients exhibited different clinical and laboratory characteristics compared to those infected by either virus alone. Coinfection of HTNV and SFTSV leads to severe and complex hemorrhagic fever. Laboratory characteristics, such as the indicators of WBC, PLT, BUN, and Cr, may differ between HFRS and SFTS. These findings have implications and provide references for the diagnosis and treatment of coinfected cases.

Impact of E. muris infection on B. burgdorferi-induced joint pathology in mice.

Tick-borne infections are increasing in the United States and around the world. The most common tick-borne disease in the United States is Lyme disease caused by infection with the spirochete Borrelia burgdorferi (Bb), and pathogenesis varies from subclinical to severe. Bb infection is transmitted by Ixodes ticks, which can carry multiple other microbial pathogens, including Ehrlichia species. To address how the simultaneous inoculation of a distinct pathogen impacted the course of Bb-induced disease, we used C57BL/6 (B6) mice which are susceptible to Bb infection but develop only mild joint pathology. While infection of B6 mice with Bb alone resulted in minimal inflammatory responses, mice co-infected with both Bb and the obligate intracellular pathogen Ehrlichia muris (Em) displayed hematologic changes, inflammatory cytokine production, and emergency myelopoiesis similar to what was observed in mice infected only with Em. Moreover, infection of B6 mice with Bb alone resulted in no detectable joint inflammation, whereas mice co-infected with both Em and Bb exhibited significant inflammation of the ankle joint. Our findings support the concept that co-infection with Ehrlichia can exacerbate inflammation, resulting in more severe Bb-induced disease.

Identification of Anaplasma marginale adhesins for bovine erythrocytes using phage display

Bovine anaplasmosis, caused by Anaplasma marginale, is one of the most common tick-borne diseases of cattle and has a worldwide distribution. The high costs of bovine anaplasmosis are due to treatment, decreased production, and outbreaks resulting in high mortality. The impact of bovine anaplasmosis is greatest in tropical and subtropical regions where tick vectors are abundant year around. Prevention generally relies on the use of tetracyclines to prevent disease and acaricides to reduce tick burdens. Thus, additional methods to prevent disease while reducing the use of antibiotics are needed. Protection can be reliably achieved with immunization using outer membrane proteins, thus allowing for the possibility for development of a recombinant vaccine. However, prioritizing the selection and testing of antigens from the protective outer membrane extract remains a challenge. Because A. marginale is an obligate intracellular pathogen, surface proteins that mediate adhesion to host cells, primarily red blood cells (RBCs), are functionally relevant vaccine candidates. With some exceptions, the proteins that bind RBCs remain unknown. To address this gap, a phage display library expressing 66 A. marginale proteins was screened to identify adhesins for bovine RBCs. Of the screened proteins, 73% were eliminated due to poor binding to RBCs. Several potential adhesins were identified, including Msp1b and OmpA, which are known adhesions for bovine RBCs and tick cells, respectively. Additionally, Mlp3, Am779, Msp3, and Omp13 met the criteria as RBCs adhesins and may serve as high priority vaccine candidates for future testing.

Molecular detection of piroplasms in domestic donkeys in Xinjiang, China.

Piroplasmosis is a common and prevalent tick-borne disease that affects equids. To determine the infection and molecular characteristics of the piroplasms in donkeys from Xinjiang, northwestern China, we undertook a cross sectional study by collecting representative samples across several counties within the region. A total of 344 blood samples were collected from adult domestic donkeys from 13 counties in Xinjiang. PCR was conducted to test for T. equi and B. caballi in the blood samples based on the equine merozoite antigen-1 (Ema-1) gene and the 48kDa rhoptry protein (BC48) gene, respectively. Sixteen blood samples tested positive for piroplasms and the overall infection rate was 4.7% (16/344). Seven of the 13 counties were positive for piroplasms. Among the 16 piroplasm-positive samples, 15 were singly infected with T. equi with an infection rate of 4.4% (15/344), and coinfection with T. equi and B. caballi was detected in one sample (0.3%, 1/344) from Wushi. Four T. equi sequence genotypes were identified and grouped into different branches of the evolutionary trees. These findings suggest that the infection rate of piroplasms is low in domestic donkeys in southern Xinjiang and that T. equi genotypes have a regional distribution.

RPA-CRISPR/Cas12a assay for the diagnosis of bovine Anaplasma marginale infection

Anaplasma marginale infection is one of the most common tick-borne diseases, causing a substantial loss in the beef and dairy production industries. Once infected, the pathogen remains in the cattle for life, allowing the parasites to spread to healthy animals. Since clinical manifestations of anaplasmosis occur late in the disease, a sensitive, accurate, and affordable pathogen identification is crucial in preventing and controlling the infection. To this end, we developed an RPA-CRISPR/Cas12a assay specific to A. marginale infection in bovines targeting the msp4 gene. Our assay is performed at one moderately high temperature, producing fluorescent signals or positive readout of a lateral flow dipstick, which is as sensitive as conventional PCR-based DNA amplification. This RPA-CRISPR/Cas12a assay can detect as few as 4 copies/μl of Anaplasma using msp4 marker without cross-reactivity to other common bovine pathogens. Lyophilized components of the assay can be stored at room temperature for an extended period, indicating its potential for field diagnosis and low-resource settings of anaplasmosis in bovines.

Effects of rodent abundance on ticks and Borrelia: results from an experimental and observational study in an island system

BackgroundLyme borreliosis is the most common tick-borne disease in Europe and is often caused by Borrelia afzelii, which is transmitted by Ixodes ricinus ticks. The prevalence and abundance of infected ticks fluctuate in time and space, influencing human infection risk. Rodents are reservoir hosts for B. afzelii and important feeding hosts for larval ticks. In the study reported here, we examined how variation in rodent abundance is associated with B. afzelii infection prevalence in ticks, the density of nymphs (DON) and the density of infected nymphs (DIN) in the following year. We further analysed the relationships between the abundance of infected rodents and nymphal infection prevalence (NIP) and DIN.MethodsWe conducted a study that combined experimental and observational approaches on 15 islands (10 small islands and 5 large islands) in Finland. On all of the islands, ticks and rodents were monitored and sampled during the summer of 2019, with the monitoring of tick abundance and sampling continuing into the spring of 2020. On five of the 10 small islands, captured rodents were removed from the island (“removal” islands), and on the other five small islands, captured rodents were released back to the trapping site after marking and sampling (“control” islands). On the five large islands, captured rodents were released back to the trapping site after marking and sampling. The presence of B. afzelii from nymph and rodent samples was examined.ResultsThe results of the experimental study showed that neither treatment (removal), rodent abundance index nor abundance index of infected rodents in 2019 was associated with DON, NIP or DIN in 2020. Based on data from the observational study, the NIP in 2020 decreased with increasing rodent abundance index and abundance index of infected rodents in 2019. However, the DIN in 2020 was not associated with the rodent abundance index or the abundance index of infected rodents in 2019. In addition, in the observational study, DON in 2020 increased with increasing rodent abundance index.ConclusionsOur results suggest that low rodent abundance during the tick activity period is not sufficient for reducing the disease hazard and, hence, rodent removal may not be a feasible control measure in natural ecosystems.Graphical abstract

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

BackgroundGenetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms.MethodsWe 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.ResultsWe 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.ConclusionsSusceptibility 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 registrationThe LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015–02-13).

Cascading impacts of overstory structure in managed forests on understory structure, microclimate conditions, and Ixodes scapularis (Acari: Ixodidae) densities.

Forest management practices designed to meet varied landowner objectives affect wildlife habitat and may interrupt the life-cycle stages of disease vectors, including the black-legged tick, Ixodes scapularis Say (Acari: Ixodidae). Ixodes scapularis transmits multiple pathogens including Borrelia burgdorferi, the causative agent of Lyme disease, which is the most common tick-borne disease in the United States. There is evidence that a range of active forest management practices (e.g., invasive plant removal, prescribed burning) can alter tick densities and pathogen transmission. However, few studies have investigated relationships between forest stand structural variables commonly manipulated by timber harvesting and tick ecology. Foresters may harvest timber to create certain forest structural conditions like the mean number of trees, or basal area, per hectare. This study used a spatially replicated experiment in a blocked design to compare forest stands with a range of overstory structures and document variations in the midstory, understory, and forest floor, as well as microclimate conditions within tick off-host habitat. Greater numbers of trees or basal area per hectare correlated with greater canopy closure but less understory cover, stabilized microclimate temperature, higher microclimate humidity, and greater I. scapularis nymph densities. A random forest model identified understory forest structure as the strongest predictor of nymph densities. There was no relationship between the number of trees or basal area per hectare and daily deer (Odocoileus virginianus Zimmermann) activity or nymphal infection prevalence. These findings provide a deeper understanding of tick-habitat associations within a forest stand and have the potential to inform forest management decisions.

Incidence of Lyme Borreliosis in Germany: A retrospective observational healthcare claims study

Lyme borreliosis (LB) is the most common tick–borne disease in Germany. Although the incidence of LB in Germany has been assessed in several studies, those studies either used data from statutory surveillance, which frequently underreport cases, or data from health claims databases, which may overestimate cases due to non–specific LB case definitions. Here, using a more specific case definition, we describe the incidence of medically–attended LB by disease manifestation, age group, and federal state for the period 2015–2019. Both inpatient and outpatient cases were analyzed from a claims database. To be eligible for inclusion, patients were required to have an LB specific ICD–10 GM diagnosis code plus an antibiotic prescription, and for disseminated manifestations, a laboratory test order additionally. LB cases were classified as erythema migrans (EM), or disseminated disease including Lyme arthritis (LA), Lyme neuroborreliosis (LNB), and all other disease manifestations (OTH). Between 2015 and 2019, the incidence of medically–attended LB cases ranged from 195.7/100,000 population per year (95% confidence interval [CI], 191.0 – 200.5) to 254.5/100,000 population per year (95% CI, 249.0 – 260.0) per year. The majority of cases (92.2%) were EM, while 2.8% presented as LA, 3.8% as LNB, and 1.2% as OTH. For both EM and disseminated disease, the incidence peaked in children aged 5–9 years and in older adults. By federal state, the incidence of medically–attended EM ranged from 74.4/100,000 population per year (95% CI, 71.9 – 77.0) per year in Hamburg, to 394.1/100,000 population per year (95% CI, 370.7 – 417.6) per year in Saxony, whereas for medically–attended disseminated disease, the highest incidence was in Thuringia, Saxony, and Bavaria (range: 22.0 [95% CI, 19.9 – 24.0] to 35.7 [95% CI, 34.7 – 36.7] per 100,000 population per year). This study comprehensively estimated the incidence of all manifestations of medically–attended LB and showed a high incidence of LB throughout Germany. Results from the study support performing epidemiological studies in all federal states to measure the burden of LB and to invest in public health interventions for prevention.

Antibody responses to immunoevasion proteins BBK32 and OspE constitute part of the serological footprint in neuroborreliosis but are insufficient to prevent the disease.

Lyme borreliosis, caused by Borrelia burgdorferi sensu lato, is the most common tickborne disease. Its neuronal form, neuroborreliosis, comprises 3 to 38% of borreliosis cases in Europe. Borrelia outer surface proteins and virulence factors, OspE and BBK32, have been previously reported to help cause infection by promoting attachment to human host epithelial cells and evading complement attack. We assessed the serological responses to BBK32 and OspE in 19 individuals diagnosed with neuroborreliosis to see whether antibodies that could both target the bacteria and neutralize the virulence mechanisms on the microbial surface emerge. Results evaluate levels of total protein, IgG and the chemokine CXCL13, a determinant for B-cell recruitment during neuroinflammation, in patients' cerebrospinal fluid samples. Antibody levels against BBK32 and OspE correlated with those against VlsE, a well-characterized diagnostic serological marker of the disease. A dual serological profile of the patients was observed. K-means clustering split the cohort into two discrete groups presenting distinct serological and CNS responses. One group contained young patients with low levels of anti-BBK32 and OspE antibodies. The other group showed stronger responses, possibly following prolonged infections or reinfections. Additionally, we assessed anti-ganglioside antibodies that could cause autoimmunity or complement dysregulation but observed that they did not correlate with neuroborreliosis in our patient cohort. The dual nature of antibody responses against the virulence factors BBK32 and OspE in neuroborreliosis patients may suggest the necessity of repeated exposures for efficient immune responses. Better protection could be achieved if the virulence factors were formulated into vaccines.

Assessing the Influence of Climate Change and Environmental Factors on the Top Tick-Borne Diseases in the United States: A Systematic Review.

In the United States (US), tick-borne diseases (TBDs) have more than doubled in the past fifteen years and are a major contributor to the overall burden of vector-borne diseases. The most common TBDs in the US-Lyme disease, rickettsioses (including Rocky Mountain spotted fever), and anaplasmosis-have gradually shifted in recent years, resulting in increased morbidity and mortality. In this systematic review, we examined climate change and other environmental factors that have influenced the epidemiology of these TBDs in the US while highlighting the opportunities for a One Health approach to mitigating their impact. We searched Medline Plus, PUBMED, and Google Scholar for studies focused on these three TBDs in the US from January 2018 to August 2023. Data selection and extraction were completed using Covidence, and the risk of bias was assessed with the ROBINS-I tool. The review included 84 papers covering multiple states across the US. We found that climate, seasonality and temporality, and land use are important environmental factors that impact the epidemiology and patterns of TBDs. The emerging trends, influenced by environmental factors, emphasize the need for region-specific research to aid in the prediction and prevention of TBDs.

Paretic complications of tick-borne encephalitis and Lyme neuroborreliosis in the Czech Republic: Characteristics and clinical outcome

Tick-borne encephalitis (TBE) and Lyme neuroborreliosis (LNB), the most common tick-borne diseases of the central nervous system in Central Europe, are frequently associated with pareses. The aim of this study was to characterise paretic complications in patients with TBE and LNB, including their severity, persistence and impact on the patients' quality of life. Our retrospective observational study included patients with aseptic CNS infection due to TBE virus or Borrelia burgdorferi sensu lato. Paretic complications were evaluated in the acute phase and the patients were followed up until complete regression or long-term stabilisation of any neurological deficit. The severity of the neurological deficit was graded according to the modified Rankin Scale (mRS).A total of 823 patients (582 with TBE, 241 with LNB) was included. Paretic complications were diagnosed in 63 TBE patients (10.8 %) and in 147 LNB patients (61.0 %). In TBE, the most common neurological deficit was brachial plexus paresis in 21 patients (33 %) and bulbar symptoms in 18 patients (29 %). In LNB patients, facial nerve palsy was the most frequent neurological deficit (117patients; 79.6 %), followed by lower limb paresis in 23 patients (15.6 %). Forty-nine TBE patients and 134 LNB paretic patients completed follow-up. Paresis resolved within 3 weeks in 16 TBE patients (33 %) and 53 LNB patients (39.5 %), but the proportion of patients with paresis persisting for more than 12 months was significantly higher in TBE (34.7 vs. 3.7 %, p < 0.001). The mean mRS was significantly higher in TBE paretic patients compared to LNB (p < 0.001).Paretic complications are significantly more common in LNB than in TBE but pareses associated with TBE last longer than in LNB and considerably reduce the quality of life of patients. Prevention remains the only way to influence the long-term motor deficits of TBE.

Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi.

Lyme disease, the most common tick-borne infectious disease in the US, is caused by a spirochetal pathogen Borrelia burgdorferi (Bb). Distinct host responses are observed in susceptible and resistant strains of inbred of mice following infection with Bb reflecting a subset of inflammatory responses observed in human Lyme disease. The advent of post-genomic methodologies and genomic data sets enables dissecting the host responses to advance therapeutic options for limiting the pathogen transmission and/or treatment of Lyme disease. In this study, we used single-cell RNA-Seq analysis in conjunction with mouse genomics exploiting GFP-expressing Bb to sort GFP+ splenocytes and GFP- bystander cells to uncover novel molecular and cellular signatures that contribute to early stages of immune responses against Bb. These data decoded the heterogeneity of splenic neutrophils, macrophages, NK cells, B cells, and T cells in C3H/HeN mice in response to Bb infection. Increased mRNA abundance of apoptosis-related genes was observed in neutrophils and macrophages clustered from GFP+ splenocytes. Moreover, complement-mediated phagocytosis-related genes such as C1q and Ficolin were elevated in an inflammatory macrophage subset, suggesting upregulation of these genes during the interaction of macrophages with Bb-infected neutrophils. In addition, the role of DUSP1 in regulating the expression of Casp3 and pro-inflammatory cytokines Cxcl1, Cxcl2, Il1b, and Ccl5 in Bb-infected neutrophils were identified. These findings serve as a growing catalog of cell phenotypes/biomarkers among murine splenocytes that can be exploited for limiting spirochetal burden to limit the transmission of the agent of Lyme disease to humans via reservoir hosts.

Bacterial Vector-Borne Zoonotic Diseases and One Health Approach. A Review

Abstract One Health is a collaborative, multisectoral, and transdisciplinary approach with the goal of achieving optimal health outcomes recognizing the interconnection between people, animals, plants, and their shared environments. The main goal of this paper is to highlight the significance of the One Health concept in relation to the large group of diseases that transmits through arthropods and their worldwide distribution, with a closer look at the zoonoses. The importance of knowledge increases as the globalization and climate changes increases the likelihood of transmission, as both cause favourable conditions for transmission of bacteria and viruses. The increase in reservoir abundance, climate change, changing habitat structure, socio-political changes, and import of animals for welfare reasons, trade and traveling are considered to be potential factors for the pathogen and vector introductions to new areas. This article highlights the selected agents of bacterial zoonoses as sources of human and animal diseases and shows the number of cases of Lyme disease, which is the most common bacterial tick-borne disease in humans in Slovakia and Norway, and the trend in incidence over the past twelve years.