Stages Of Lyme Disease Research Articles

Current and future burden from Lyme disease in Québec as a result of climate change.

Environmental changes will foster the spread of Ixodes scapularis ticks and increase the incidence of Lyme disease in Québec in the coming years. The objective of this study is to estimate the epidemiological and clinical burden and part of the current economic burden of Lyme disease in Québec and to estimate the number of cases expected by 2050. Cases of Lyme disease reported in Québec from 2015 to 2019 were used to describe their demographic, geographical and clinical characteristics and the cost of their initial care. Three incidence rate scenarios were then developed to estimate the number of cases expected by 2050, based on demographic and climate projections. From 2016 to 2019, 1,473 cases of Lyme disease were reported in Québec. Over 90% of those cases were acquired in two regions of southern Québec (Estrie and Montérégie), while the individuals infected were residents from all over Québec. The average age of cases is 44 years and 66% of infections were at the localized stage, the first stage of Lyme disease. The cost of initial care is estimated at an average of $182 CAN per patient ($47 CAN at the localized stage and $443 CAN at the disseminated stage). According to projections, over 95% of the Québec population will live in a climate zone conducive to the establishment of ticks by 2050, with a number of cases acquired in Québec being 1.3 to 14.5 times higher than in 2019, depending on the incidence rate scenario used. The epidemiological burden is concentrated primarily in southern Québec, but the clinical and economic burden is already distributed throughout the province. The projections for 2050 should help the regions of Québec adapt and optimize public health protection measures.

A Comparison of Lyme Serological Testing Platforms with a Panel of Clinically Characterized Samples from Various Stages of Lyme Disease

In 2019, the CDC updated serology testing guidelines for Lyme disease diagnosis to include alternative modified two-tiered testing that replaces the western blots of standard testing with an additional ELISA. Antibody-capture serological assays have also been used as an aid for Lyme diagnosis. A panel of clinically characterized samples from the CDC was tested to compare modified two-tiered testing to the standard two-tiered algorithm and an antibody capture immunoassay. A CDC panel of 92 samples comprised a range of samples including early Lyme, Lyme neuroborreliosis, Lyme arthritis, infections by other pathogens, and healthy controls. The panel was tested on a standard two-tiered platform by the CDC, the ZEUS Borrelia Test System for modified two-tiered testing, and a lab-developed antibody-capture serological assay. Sensitivity and specificity results from each assay were compared to determine significance. The antibody-capture assay demonstrated increased sensitivity but decreased specificity compared to the modified and standard two-tiered platforms. There was no statistical difference found between the modified and standard two-tiered platforms. Improved sensitivity of antibody-capture when testing early Lyme disease samples is offset by decreased specificity, especially with syphilis-positive samples. Modified two-tiered testing is similar to standard two-tiered methods while also being more scalable and simpler to interpret.

Risk factors for Lyme disease stage and manifestation using electronic health records

BackgroundLittle is known about risk factors for early (e.g., erythema migrans) and disseminated Lyme disease manifestations, such as arthritis, neurological complications, and carditis. No study has used both diagnoses and free text to classify Lyme disease by disease stage and manifestation.MethodsWe identified Lyme disease cases in 2012–2016 in the electronic health record (EHR) of a large, integrated health system in Pennsylvania. We developed a rule-based text-matching algorithm using regular expressions to extract clinical data from free text. Lyme disease cases were then classified by stage and manifestation using data from both diagnoses and free text. Among cases classified by stage, we evaluated individual, community, and health care variables as predictors of disseminated stage (vs. early) disease using Poisson regression models with robust errors. Final models adjusted for sociodemographic factors, receipt of Medical Assistance (i.e., Medicaid, a proxy for low socioeconomic status), primary care contact, setting of diagnosis, season of diagnosis, and urban/rural status.ResultsAmong 7310 cases of Lyme disease, we classified 62% by stage. Overall, 23% were classified using both diagnoses and text, 26% were classified using diagnoses only, and 13% were classified using text only. Among the staged diagnoses (n = 4530), 30% were disseminated stage (762 arthritis, 426 neurological manifestations, 76 carditis, 95 secondary erythema migrans, and 76 other manifestations). In adjusted models, we found that persons on Medical Assistance at least 50% of time under observation, compared to never users, had a higher risk (risk ratio [95% confidence interval]) of disseminated Lyme disease (1.20 [1.05, 1.37]). Primary care contact (0.59 [0.54, 0.64]) and diagnosis in the urgent care (0.22 [0.17, 0.29]), compared to the outpatient setting, were associated with lower risk of disseminated Lyme disease.ConclusionsThe associations between insurance payor, primary care status, and diagnostic setting with disseminated Lyme disease suggest that lower socioeconomic status and less health care access could be linked with disseminated stage Lyme disease. Intervening on these factors could reduce the individual and health care burden of disseminated Lyme disease. Our findings demonstrate the value of both diagnostic and narrative text data to identify Lyme disease manifestations in the EHR.

Presentation of Acrodermatitis Chronica Atrophicans Rashes on Lyme Disease Patients in Canada

Lyme disease (Lyme borreliosis) is a complex multisystem illness with varying clinical manifestations. This tick-borne zoonosis is caused by the spirochetal bacterium, Borrelia burgdorferi sensu lato (Bbsl) and, worldwide, presents with at least 20 different types of rashes. Certain cutaneous rashes are inherently interconnected to various stages of Lyme disease. In this study, five Canadian Lyme disease patients from a multi-age range presented various phases of the acrodermatitis chronica atrophicans (ACA) rash. In each case of ACA, the underlying etiological pathogen was the Lyme disease spirochete. Although ACA rashes are normally found on the lower extremities, this study illustrates that ACA rashes are not directly correlated with a tick bite, geographic area, age, Bbsl genospecies, exercise, or any given surface area of the body. Case 4 provides confirmation for an ACA rash and gestational Lyme disease. One patient (Case 5) puts forth a Bbsl and Bartonella sp. co-infection with a complex ACA rash. This study documents ACA rashes on Lyme disease patients for the first time in Canada.

Characterization of a Borrelia miyamotoi membrane antigen (BmaA) for serodiagnosis of Borrelia miyamotoi disease

Borrelia miyamotoi is a tick-borne pathogen that causes Borrelia miyamotoi disease (BMD), an emerging infectious disease of increasing public health significance. B. miyamotoi is transmitted by the same tick vector (Ixodes spp.) as B. burgdorferi sensu lato (s.l.), the causative agent of Lyme disease, therefore laboratory assays to differentiate BMD from Lyme disease are needed to avoid misdiagnoses and for disease confirmation. We previously performed a global immunoproteomic analysis of the murine host antibody response against B. miyamotoi infection to discover antigens that could serologically distinguish the two infections. An initial assessment identified a putative lipoprotein antigen, here termed BmaA, as a promising candidate to augment current research-based serological assays. In this study, we show that BmaA is an outer surface-associated protein by its susceptibility to protease digestion. Synthesis of BmaA in culture was independent of temperature at either 23 °C or 34 °C. The BmaA gene is present in two identical loci harbored on separate plasmids in North American strains LB-2001 and CT13-2396. bmaA-like sequences are present in other B. miyamotoi strains and relapsing fever borrelia as multicopy genes and as paralogous or orthologous gene families. IgM and IgG antibodies in pooled serum from BMD patients reacted with native BmaA fractionated by 2-dimensional gel electrophoresis and identified by mass spectrometry. IgG against recombinant BmaA was detected in 4 of 5 BMD patient serum samples as compared with 1 of 23 serum samples collected from patients with various stages of Lyme disease. Human anti-B. turicatae serum did not seroreact with recombinant BmaA suggesting a role as a species-specific diagnostic antigen. These results demonstrated that BmaA elicits a human host antibody response during B. miyamotoi infection but not in a tested group of B. burgdorferi-infected Lyme disease patients, thereby providing a potentially useful addition for developing BMD serodiagnostic tests.

Erken Evre Lyme Hastalığı Tanısı Konulan İki Olgu Sunumu

Lyme hastalığı, ixodes türü keneler tarafından taşınan bir spiroket olan Borrelia burgdorferi'nin neden olduğu multisistemik enfeksiyöz bir hastalıktır. Yaz aylarında sık görülmektedir. Kırsal ve ormanlık alanlarda yaşayanlarda risk daha fazladır. Klinik bulgular enfeksiyonun seyri boyunca evrelere göre değişmektedir. Lyme hastalığının erken tanısı deri bulgularının tanınmasına bağlıdır ki tüm hastaların yaklaşık %60-80'i deri bulguları göstermektedir. Başlıca kutanöz işareti de eritema migranstır. Serolojik testler klinik tanının desteklenmesi için kullanılabilmektedir. Erken dönemde teşhis edilebilirse tamamıyla tedavi edilebilen bir hastalıktır, tedavi edilmemiş hastalarda kronik artrit ve ciddi nörolojik bulgular ortaya çıkabilmektedir. Tedavide ilk seçenek, doksisiklin ve amoksisilindir. Bu çalışmada, eritema migrans tanısı konularak serolojik olarak doğrulanmış iki erken lokalize Lyme olgumuz, Batı Karadeniz Bölgesi'nin endemik olduğunu belirtmek ve sık görülmeyen hastalığı tekrar hatırlatmak amacıyla sunulmuştur.

Evaluation of in vivo expressed Borrelia burgdorferi antigens for improved IgM serodiagnosis of early Lyme disease

Improved serologic tests are needed for accurate diagnosis and proper treatment of early stage Lyme disease. We evaluated the 3 antigens currently used for 2-tiered IgM immunoblot testing (FlaB, OspC, and BmpA) in combination with 3 additional antigens (BBA65, BBA70, and BBA73) and measured the sensitivity and specificity against a serum repository of positive and negative controls. Using 3 statistical methods for positivity cutoff determinations and scoring criteria, we found increased sensitivities for early Lyme disease when 2 of 6 antigens were positive as compared with the 2 of 3 antigen IgM criteria currently used for second-tier immunoblot scoring. Specificities for negative controls were comparable or superior to using 2 of 3 antigens. These results indicate that IgM sensitivity and specificity of serological testing for Lyme disease in the early stages of illness can be improved by employing antigens that target the initial host antibody responses.

Correlation of Lyme Disease-Associated IgG4 Autoantibodies With Synovial Pathology in Antibiotic-Refractory Lyme Arthritis.

To determine whether IgG subclasses of Borrelia burgdorferi antibodies differ from those of 3 Lyme disease (LD)-associated autoantibodies. IgG antibody subclasses were determined by enzyme-linked immunosorbent assay in serum samples from 215 patients with features representative of each of the 3 stages of LD. Antibody and cytokine profiles were measured in matched serum and synovial fluid (SF) samples from patients with Lyme arthritis. Synovial tissue from patients with antibiotic-refractory arthritis was examined for histologic features, IgG subclasses of plasma cells, and messenger RNA (mRNA) subclass expression. B burgdorferi antibodies were primarily of the IgG1 and IgG3 subclasses, and the levels increased as the infection progressed. In contrast, LD-associated autoantibodies were mainly of the IgG2 and IgG4 subclasses, and these responses were found primarily in patients with either antibiotic-refractory or antibiotic-responsive arthritis, particularly in SF. However, compared with the responsive group, the inflammatory milieu in SF in the refractory group was enriched for cytokines representative of innate, Th1, Th2, and Th17 responses. Synovial tissue in a subgroup of patients with refractory arthritis showed marked expression of mRNA for IgG4 antibodies and large numbers of IgG4-staining plasma cells. IgG4 autoantibodies in SF to each of the 3 LD-associated autoantigens correlated with the magnitude of obliterative microvascular lesions and fibrosis in the tissue. Our findings indicate that the subclasses of IgG antibodies to B burgdorferi differ from those of LD-associated autoantibodies. Furthermore, the correlation of IgG4 autoantibodies with specific synovial pathology in the refractory group suggests a role for these autoantibodies, either protective or pathologic, in antibiotic-refractory Lyme arthritis.

Assessment of a diurnal blood pressure profile in patients with acute Lyme borreliosis

Aim. The purpose of the study was to investigate the character of changes in daily blood pressure profiles and to evaluate the influence of Borrelia burgdorferi infection on the course of essential hypertension in patients with acute stage of Lyme disease.Methods. 37 patients with an acute stage of Lyme disease were examined and broken down in two groups. The first group included 18 patients without essential hypertension. 19 patients with stage II of essential hypertension were included into group II. The group of comparison consisted of 32 patients with stage II of essential hypertension without Lyme disease. 26 healthy volunteers of the control group were comparable in gender and age.Results. A significant difference of the average diastolic blood pressure index during night time in patients with acute stage of Lyme disease and essential hypertension 90.0 (68.5–100.0) mm Hg versus the control group 77.0 (65.0–86.0) mm Hg at p = 0.03 was observed. When determining a type of daily blood pressure profile, some features of a blood pressure circadian rhythm were found in all groups of patients. There were ‘Dipper’ (77.7%) and ‘Non-Dipper’ (22.3%) profiles in the group of patients with acute stage of Lyme disease without essential hypertension. No ‘Over-Dipper’ and ‘Night-Peaker’ profiles were recorded in this group. 'Dipper’ (20.0%), ‘Non-Dipper’ (73.4%) and ‘Night-Peaker’ (6.6%) blood pressure profiles were typical for patients with acute stage of Lyme disease and essential hypertension. Conclusion. A 22.3% decrease in the number of patients with a ‘Dipper’ blood pressure daily profile and an equal increase in the number of ‘non-dipper’ patients are characteristic of an acute stage of Lyme disease. The number of ‘Non-Dipper’ patients with essential hypertension and acute stage of Lyme disease increases up to 73.4%. Thus, acute Lyme disease and essential hypertension tend to burden the each other’s course.Received 10 May 2017. Revised 7 September 2017. Accepted 25 September 2017.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributionsConception and study design: A.V. Sandugei, M.V. Ilyin, O.A. Khrustalev, N.S. Baranova. Data collection and analysis: A.V. Sandugei, O.A. Khrustalev, N.V. Emanuilova. Statistical data analysis: A.V. Sandugei, N.V. Emanuilova, O.Yu. Churakov.Drafting the article: A.V. Sandugei, N.V. Emanuilova, V.V. Neusypin. Critical revision of the article: A.V. Sandugei, N.V. Emanuilova, V.V. Neusypin.Final approval of the version to be published: A.V. Sandugei, M.V. Ilyin, O.A. Khrustalev, N.S. Baranova, N.V. Emanuilova, O.Yu. Churakov, V.V. Neusypin

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research.

There has been an increasing incidence of Lyme disease (LD) in Canada and the United States corresponding to the expanding range of the Ixodes tick vector and Lyme disease agent (Borrelia burgdorferi sensu stricto). There are many diagnostic tests for LD available in North America, all of which have some performance issues, and physicians are concerned about the appropriate use and interpretation of these tests. The objective of this systematic review is to summarize the North American evidence on the accuracy of diagnostic tests and test regimes at various stages of LD. Included in the review are 48 studies on diagnostic tests used in North America published since 1995. Thirteen studies examined a two-tier serological test protocol vs. clinical diagnosis, 24 studies examined single assays vs. clinical diagnosis, 9 studies examined single immunoblot vs. clinical diagnosis, 7 studies compared culture or PCR direct detection methods vs. clinical diagnosis, 22 studies compared two or more tests with each other and 8 studies compared a two-tiered serological test protocol to another test. Recent studies examining the sensitivity and specificity of various test protocols noted that the Immunetics® C6 B. burgdorferi ELISA™ and the two tier approach have superior specificity compared to proposed replacements, and the CDC recommended western blot algorithm has equivalent or superior specificity over other proposed test algorithms. There is a dramatic increase in test sensitivity with progression of B. burgdorferi infection from early to late LD. Direct detection methods, culture and PCR of tissue or blood samples were not as sensitive or timely compared to serological testing. It was also noted that there are a large number of both commercial (n = 42) and in-house developed tests used by private laboratories which have not been evaluated in the primary literature.

Cimetidine as a novel adjunctive treatment for early stage Lyme disease

Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most common vector-borne illness in the United States. It is a complex disease which may affect the skin, joints, heart, eyes, and central nervous system. Prompt diagnosis and treatment is curative in most instances. However, a significant percentage of patients experience ongoing symptoms after treatment. Currently, there is much controversy regarding the diagnosis, pathophysiology, and treatment of Lyme disease. Pathogen persistence despite treatment lies at the heart of this debate.Many believe that the ongoing symptoms are due to factors such as autoimmunity or permanent damage that is incurred during the active infection. However, there is an emerging school of thought that states that ongoing symptoms are due to a persistent infection that is able to survive both the immune response and antibiotic therapy. Numerous studies have shown that Bb can indeed persist within the host despite treatment and several mechanisms have been proposed to explain Bb’s persistence capabilities. These include: polymorphism, antigenic variance, biofilm formation, persister cells, and immunomodulation.There is evidence that Bb is able to alter cytokine profiles within the host which may allow the organism to survive the immune response. This immunomodulation follows a pattern of T-helper 1 (TH1) suppression in favor of T-helper 2 (TH2) processes. In contrast, it has been shown that the optimal immune response to Bb infection involves an early, robust TH1 response and a later conversion to TH2 dominance once the infection is controlled or cleared. It has been proposed that a reconstitution of proper immune-competency in the infected host may improve clinical outcomes in Lyme disease.Cimetidine (CIM) is an over-the-counter histamine-2 (H2) antagonist that is primarily used to lower acid secretions in the stomach. T-regulatory (Treg) cells also possess the H2 receptor, which has spurred interest in CIM as a potential immunomodulator. CIM therapy has been shown to increase levels of the TH1 associated cytokines IL-12, TNF-α, and IFN-γ while decreasing levels of the TH2 associated cytokine IL-10. The author proposes a novel theory that CIM therapy during early Bb infection may promote a more appropriate immune response and increase the utility of antibiotic therapy during early stage Lyme disease, thus improving clinical outcomes of the disease.

Polymorphism of 41 kD Flagellin Gene and Its Human B-Cell Epitope in Borrelia burgdorferi Strains of China.

The 41 kD flagellin of Borrelia burgdorferi (B. burgdorferi) is a major component of periplasmic flagellar filament core and a good candidate for serodiagnosis in early stage of Lyme disease. Here, we chose 89 B. burgdorferi strains in China, amplified the gene encoding the 41 kD flagellin, and compared the sequences. The results showed that genetic diversity presented in the 41 kD flagellin genes of all 89 strains among the four genotypes of B. burgdorferi, especially in the genotype of B. garinii. Some specific mutation sites for each genotype of the 41 kD flagellin genes were found, which could be used for genotyping B. burgdorferi strains in China. Human B-cell epitope analysis showed that thirteen of 15 nonsynonymous mutations occurred in the epitope region of 41 kD flagellin and thirty of 42 B-cell epitopes were altered due to all 13 nonsynonymous mutations in the epitope region, which may affect the function of the antigen. Nonsynonymous mutations and changed human B-cell epitopes exist in 41 kD flagellin of B. burgdorferi sensu lato strains; these changes should be considered in serodiagnosis of Lyme disease.

Collection and characterization of samples for establishment of a serum repository for lyme disease diagnostic test development and evaluation.

Serological assays and a two-tiered test algorithm are recommended for laboratory confirmation of Lyme disease. In the United States, the sensitivity of two-tiered testing using commercially available serology-based assays is dependent on the stage of infection and ranges from 30% in the early localized disease stage to near 100% in late-stage disease. Other variables, including subjectivity in reading Western blots, compliance with two-tiered recommendations, use of different first- and second-tier test combinations, and use of different test samples, all contribute to variation in two-tiered test performance. The availability and use of sample sets from well-characterized Lyme disease patients and controls are needed to better assess the performance of existing tests and for development of improved assays. To address this need, the Centers for Disease Control and Prevention and the National Institutes of Health prospectively collected sera from patients at all stages of Lyme disease, as well as healthy donors and patients with look-alike diseases. Patients and healthy controls were recruited using strict inclusion and exclusion criteria. Samples from all included patients were retrospectively characterized by two-tiered testing. The results from two-tiered testing corroborated the need for novel and improved diagnostics, particularly for laboratory diagnosis of earlier stages of infection. Furthermore, the two-tiered results provide a baseline with samples from well-characterized patients that can be used in comparing the sensitivity and specificity of novel diagnostics. Panels of sera and accompanying clinical and laboratory testing results are now available to Lyme disease serological test users and researchers developing novel tests.

Лаймская болезнь. Педиатрические аспекты (II часть)

До 25 % всех заболевших Лайм-боррелиозом — это дети в возрасте 5–9 лет. У детей также выделяют три клинико-патогенетические стадии лаймской болезни. Типичный признак боррелиоза — эритема ≥ 5 см в диаметре, возникающая в месте присасывания клеща через 1–32 дня. Диссеминация Borrelia burgdorferi s.l. обусловливает клинический полиморфизм. Клещевой боррелиоз не является акушерской инфекцией. Несмотря на адекватную антибиотикотерапию, возможно развитие постборрелиозного синдрома.

Early Lyme disease – current clinical and epidemiological aspects in Braşov

Background Lyme disease, endemic in Europe, North America and Asia, is caused by the Borrelia burgdorferi bacteria. In the absence of a correct diagnosis and an early and appropriate treatment, it evolves in 3 stages: early localized stage (erythema migrans – present in the majority but not in all the patients – fever, fatigue, myalgia, headache, neck stiffness); early disseminated stage (secondary skin lesions and extra cutaneous manifestations, like muscular/skeletal and hematologic symptoms, less common cardiac disturbance); chronic disseminated stage (rheumatological and neurological manifestations, acrodermatitis chronica atrophicans). The aim of this study was to analyze some epidemiological and clinical aspects in the early stage of Lyme disease in patients admitted into the Infectious Diseases Hospital of Brasov.

The HtrA protease of Borrelia burgdorferi degrades outer membrane protein BmpD and chemotaxis phosphatase CheX

Borrelia burgdorferi, the spirochaetal agent of Lyme disease, codes for a single HtrA protein, HtrABb (BB0104) that is homologous to DegP of Escherichia coli (41% amino acid identity). HtrABb shows physical and biochemical similarities to DegP in that it has the trimer as its fundamental unit and can degrade casein via its catalytic serine. Recombinant HtrABb exhibits proteolytic activity in vitro, while a mutant (HtrABbS198A) does not. However, HtrABb and DegP have some important differences as well. Native HtrABb occurs in both membrane-bound and soluble forms. Despite its homology to DegP, HtrABb could not complement an E. coli DegP deletion mutant. Late stage Lyme disease patients, as well as infected mice and rabbits developed a robust antibody response to HtrABb, indicating that it is a B-cell antigen. In co-immunoprecipitation studies, a number of potential binding partners for HtrABb were identified, as well as two specific proteolytic substrates, basic membrane protein D (BmpD/BB0385) and chemotaxis signal transduction phosphatase CheX (BB0671). HtrABb may function in regulating outer membrane lipoproteins and in modulating the chemotactic response of B. burgdorferi.

Unclassified cardiomyopathy or Lyme carditis? A three year follow-up

Lyme carditis can be a clinical manifestation of the early disseminated stage of Lyme disease caused by the tick-transmitted pathogen Borrelia burgdorferi. We present the case of a 41 year-old Caucasian woman referred to our hospital with symptoms of fatigue, progressive exertional dyspnoea, supraventricular cardiac arrhythmia, and an enlarged heart revealed on chest radiography. Following an untypical result of transthoracic echocardiography, cardiac magnetic resonance was performed. This showed structural cardiac changes and focus of late gadolinium enhancement in the midwall of the apex region. Further diagnostic processes, including endomyocardial biopsy and serology tests, made it possible to diagnose Lyme carditis. Clinical observation was followed-up for three years.

Lyme Disease in Northern Slovakia (1989-2010): Clinical and Epidemiological Characteristics

In recent years, the incidence of Lyme borreliosis has been on an upward trend also as a result of global warming, not only in our region. In the prospective and also retrospective study we have monitored the representation of individual forms of borreliosis in the set of 476 patients treated for this disease for the period of 22 years (1989-2010). From the total set of 476 patients, the treatment was initiated in the early localized stage in 50.84 % (n = 242), and the disease was diagnosed in the early disseminated stage of Lyme disease in 48.32 % (n = 230). The late disseminated stage of the disease has developed only in 4 cases (0.84 %). We focused on the epidemiological history- information about the tick acquisition was confirmed in 47.68 % (n = 227), the vector of the disease transmission, which is a tick in most cases, the seasonality- the highest number of cases of the disease development was in July and August: 39.92 % of the cases (n = 190), and the locality of the disease development with creating the map of sources of Lyme borreliosis in the northern region of Slovakia. We divided the set of patients also according to the risk of exposure to the vectors: the infection was transmitted to humans during recreational activities in 94.11 % (n = 448).

Microarray Analyses of Inflammation Response of Human Dermal Fibroblasts to Different Strains of Borrelia burgdorferi Sensu Stricto

In Lyme borreliosis, the skin is the key site of bacterial inoculation by the infected tick, and of cutaneous manifestations, erythema migrans and acrodermatitis chronica atrophicans. We explored the role of fibroblasts, the resident cells of the dermis, in the development of the disease. Using microarray experiments, we compared the inflammation of fibroblasts induced by three strains of Borrelia burgdorferi sensu stricto isolated from different environments and stages of Lyme disease: N40 (tick), Pbre (erythema migrans) and 1408 (acrodermatitis chronica atrophicans). The three strains exhibited a similar profile of inflammation with strong induction of chemokines (CXCL1 and IL-8) and IL-6 cytokine mainly involved in the chemoattraction of immune cells. Molecules such as TNF-alpha and NF-κB factors, metalloproteinases (MMP-1, -3 and -12) and superoxide dismutase (SOD2), also described in inflammatory and cellular events, were up-regulated. In addition, we showed that tick salivary gland extracts induce a cytotoxic effect on fibroblasts and that OspC, essential in the transmission of Borrelia to the vertebrate host, was not responsible for the secretion of inflammatory molecules by fibroblasts. Tick saliva components could facilitate the early transmission of the disease to the site of injury creating a feeding pit. Later in the development of the disease, Borrelia would intensively multiply in the skin and further disseminate to distant organs.

Acylated cholesteryl galactosides are ubiquitous glycolipid antigens amongBorrelia burgdorferi sensu lato: Figure 1

Lyme disease (LD) is the most common tick-borne disease in the Northern hemisphere. It is caused by Borrelia burgdorferi sensu lato, in particular, B. burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. However, other genospecies have been implicated as causative factors of LD as well. Borrelia burgdorferi exhibits numerous immunogenic lipoproteins, but due to strong heterogeneity, the use of these proteins for serodiagnosis and vaccination is hampered. We and others have identified acylated cholesteryl galactosides (ACGal) as a novel glycolipid present in B. burgdorferi sensu stricto, B. afzelii, and B. garinii. ACGal is a strong antigen and the majority of patients display anti-ACGal antibodies in the chronic stages of LD. However, it is unknown whether ACGal is present in other presumably pathogenic B. burgdorferi genospecies. Therefore, we performed an analysis of the total lipid extracts of a wide spectrum of genospecies of B. burgdorferi sensu lato using thin-layer chromatography as well as Western blot and dot-blot assays. We show that ACGal is present in substantial quantities in all B. burgdorferi genospecies tested. Therefore, this molecule might improve the serological detection of rarely pathogenic genospecies, and may be used as a protective vaccine regardless of the prevailing genospecies.