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Lyme disease is the most common vector-borne disease in North America and Europe. The clinical manifestations of Lyme disease vary based on the genospecies of the infecting Borrelia burgdorferi spirochete, but the microbial genetic elements underlying these associations are not known. Here, we report the whole genome sequence (WGS) and analysis of 299 B. burgdorferi (Bb) isolates derived from patients in the Eastern and Midwestern US and Central Europe. We develop a WGS-based classification of Bb isolates, confirm and extend the findings of previous single- and multi-locus typing systems, define the plasmid profiles of human-infectious Bb isolates, annotate the core and strain-variable surface lipoproteome, and identify loci associated with disseminated infection. A core genome consisting of ~900 open reading frames and a core set of plasmids consisting of lp17, lp25, lp36, lp28-3, lp28-4, lp54, and cp26 are found in nearly all isolates. Strain-variable (accessory) plasmids and genes correlate strongly with phylogeny. Using genetic association study methods, we identify an accessory genome signature associated with dissemination in humans and define the individual plasmids and genes that make up this signature. Strains within the RST1/WGS A subgroup, particularly a subset marked by the OspC type A genotype, have increased rates of dissemination in humans. OspC type A strains possess a unique set of strongly linked genetic elements including the presence of lp56 and lp28-1 plasmids and a cluster of genes that may contribute to their enhanced virulence compared to other genotypes. These features of OspC type A strains reflect a broader paradigm across Bb isolates, in which near-clonal genotypes are defined by strain-specific clusters of linked genetic elements, particularly those encoding surface-exposed lipoproteins. These clusters of genes are maintained by strain-specific patterns of plasmid occupancy and are associated with the probability of invasive infection.
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Borrelia burgdorferi , Doença de Lyme , Humanos , Borrelia burgdorferi/genética , Genótipo , Sequenciamento Completo do Genoma , Plasmídeos/genéticaRESUMO
PURPOSE: Diagnosis of (European) Lyme neuroborreliosis has been based on clinical presentation, cerebrospinal fluid (CSF) pleocytosis and demonstration of intrathecal borrelial antibody synthesis (ITBAS) to document Borrelia burgdorferi s. l. INFECTION: It is not known if other criteria to document Borrelia infection may contribute to the diagnosis. METHODS: We compared the sensitivity of three individual criteria (ITBAS, CSF Borrelia culture, and the presence of erythema migrans [EM]) to confirm the diagnosis of early Lyme neuroborreliosis in 280 patients ≥ 15 years of age evaluated at a Lyme borreliosis outpatient clinic in Slovenia. The patients had either radicular pain of new onset or involvement of a cranial nerve but without radicular pain, each in conjunction with CSF pleocytosis. Evaluation was of patients who had each of the three confirmatory criteria assessed, and for whom at least one criterion was positive. RESULTS: Analysis of 280 patients, 120 women and 160 men, median age 57 (range 15-84) years, revealed that ITBAS was the most frequently observed positive criterion (85.4%), followed by EM (52.9%), and by a positive CSF Borrelia culture (9.6%). Of the 280 patients, 154 (55%) met only one criterion (43.2% ITBAS only, 10.7% EM only, and 1.1% positive CSF culture only), whereas 42.1% met two criteria. Only 2.9% of patients were positive by all three criteria. CONCLUSION: Although ITBAS was the most frequent criterion for confirmation for Borrelia infection, the presence of EM alone confirmed an additional 10.7% of patients and a positive CSF Borrelia culture alone added another 1.1%.
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Patients who have Lyme neuroborreliosis (LNB) might experience lingering symptoms that persist despite antibiotic drug therapy. We tested whether those symptoms are caused by maladaptive immune responses by measuring 20 immune mediators in serum and cerebrospinal fluid (CSF) in 79 LNB patients followed for 1 year. At study entry, most mediators were highly concentrated in CSF, the site of the infection. Those responses resolved with antibiotic therapy, and associations between CSF cytokines and signs and symptoms of LNB were no longer observed. In contrast, subjective symptoms that persisted after use of antibiotics were associated with increased levels of serum interferon-α (IFN-α), which were already observed at study entry, and remained increased at each subsequent timepoint. Highest IFN-α levels corresponded with severe disease. Although the infection serves as the initial trigger, sequelae after antibiotic therapy are associated with unremitting systemic IFN-α levels, consistent with the pathogenic role of this cytokine in interferonopathies in other conditions.
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Neuroborreliose de Lyme , Humanos , Neuroborreliose de Lyme/tratamento farmacológico , Neuroborreliose de Lyme/diagnóstico , Interferon-alfa/uso terapêutico , Citocinas , Fatores Imunológicos , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: There is a general assumption that after deposition into skin, Lyme borreliae disseminate hematogenously to other organs, resulting in extracutaneous manifestations of Lyme borreliosis, including Lyme neuroborreliosis. However, our experience over the past 40 years, along with several published case reports that observed colocalization of radicular pain and erythema migrans (EM) in patients with borrelial meningoradiculoneuritis (Bannwarth syndrome), argues against hematogenous dissemination in Lyme neuroborreliosis. METHODS: We compared the location of EM in 112 patients with Bannwarth syndrome to 12315 EM patients without neurological involvement. Moreover, we assessed the colocalization of EM and radicular pain in patients with Bannwarth syndrome. RESULTS: Compared to >12000 EM patients without neurological involvement, patients with Bannwarth syndrome had a significantly higher frequency of EM on head/neck (6% vs 1%; P=.0005) and trunk (47% vs 24%; P<.0001), similar frequency on arms (16% vs 16%; P=.91), but lower frequency on legs (30% vs 59%; P<.0001). Moreover, in 79% (89/112) of patients the site of EM matched the dermatomes of radicular pain. The odds for a congruent location of EM and radicular pain were highly significant with the highest odds ratios (OR) observed for head (OR=221), followed by neck (OR=159), legs (OR=69), arms (OR=48), and trunk (OR=33). CONCLUSIONS: The greater frequency of EM on head/neck and trunk and the colocalization of EM with radicular pain in patients with Bannwarth syndrome suggest that central nervous system involvement in Lyme neuroborreliosis is due to a retrograde spread of borrelia from skin to the spinal cord via peripheral nerves.
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Doenças Ósseas , Borrelia , Eritema Migrans Crônico , Glossite Migratória Benigna , Doença de Lyme , Neuroborreliose de Lyme , Sistema Nervoso Central , Humanos , Neuroborreliose de Lyme/complicações , Neuroborreliose de Lyme/epidemiologia , DorRESUMO
Information on febrile illness caused by tick-borne encephalitis virus (TBEV) without central nervous system involvement is limited. We characterized 98 patients who had TBEV RNA in their blood but no central nervous system involvement at the time of evaluation. Median duration of illness was 7 days; 37 (38%) patients were hospitalized. The most frequent findings were malaise or fatigue (98%), fever (97%), headache (86%), and myalgias (54%); common laboratory findings were leukopenia (88%), thrombocytopenia (59%), and abnormal liver test results (63%). During the illness, blood leukocyte counts tended to improve, whereas thrombocytopenia and liver enzymes tended to deteriorate. At the time of positive PCR findings, 0/98 patients had serum IgG TBEV and 7 serum IgM TBEV; all patients later seroconverted. Viral RNA load was higher in patients with more severe illness but did not differ substantially in relation to several other factors. Illness progressed to tick-borne encephalitis in 84% of patients within 18 days after defervescence.
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Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Anticorpos Antivirais , Sistema Nervoso Central , Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Humanos , RNA Viral/genética , Carga ViralRESUMO
Lyme neuroborreliosis (LNB) in Europe may manifest with painful meningoradiculoneuritis (also known as Bannwarth syndrome) or lymphocytic meningitis with or without cranial neuritis (peripheral facial palsy). We assessed host immune responses and the prevalence of TLR1 (toll-like receptor 1)-1805GG polymorphism to gain insights into the pathophysiology of these conditions. Regardless of LNB manifestation, most mediators associated with innate and adaptive immune responses were concentrated in cerebrospinal fluid; serum levels were unremarkable. When stratified by specific clinical manifestation, patients with meningoradiculoneuritis had higher levels of B-cell chemoattractants CXC motif chemokine ligand (CXCL) 12 and CXCL13 and T-cell-associated mediators CXCL9, CXCL10, and interleukin 17, compared with those without radicular pain. Moreover, these patients had a higher frequency of TLR1-1805GG polymorphism and more constitutional symptoms. These findings demonstrate that meningoradiculoneuritis is a distinct clinical entity with unique immune and genetic pathophysiology, providing new considerations for the study of LNB and borrelial meningoradiculitis.
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Borrelia , Citocinas , Paralisia Facial , Neuroborreliose de Lyme , Quimiocinas/metabolismo , Citocinas/metabolismo , Europa (Continente) , Humanos , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Neuroborreliose de Lyme/genética , PrevalênciaRESUMO
BACKGROUND: Information on the course and outcome of early European Lyme neuroborreliosis is limited. METHODS: The study comprised 77 patients (38 males, 39 females; median age, 58 years) diagnosed with painful meningoradiculitis (Bannwarth syndrome) who were followed up for 1 year at a single center. RESULTS: Duration of neurological symptoms before diagnosis was 30 (interquartile range, 14-50) days. The most frequent symptoms/signs were radicular pain (100%), sleep disturbances (75.3%), erythema migrans (59.7%), headache (46.8%), fatigue (44.2%), malaise (39%), paresthesias (32.5%), peripheral facial palsy (PFP) (36.4%), meningeal signs (19.5%), and pareses (7.8%). Cerebrospinal fluid (CSF) analysis revealed lymphocytic/monocytic pleocytosis, elevated protein concentration, and intrathecal synthesis of borrelial immunoglobulin M and immunoglobulin G antibody in 100%, 81.1%, 63%, and 88.7% of patients, respectively. Borreliae (predominantly Borrelia garinii) were isolated from CSF, skin, and blood in 15.6%, 40.6%, and 2.7% of patients, respectively. The outcome after 14-day treatment with ceftriaxone was favorable in 87.8% of patients. Control CSF examination at 3 months showed decreased leukocyte counts in all patients; however, 23.3% still had pleocytosis (>10 × 10(6) cells/L). A model based on pretreatment data and the findings at the end of 14-day antibiotic treatment accurately predicted which patients would have an unfavorable outcome 6 or 12 months after treatment. CONCLUSIONS: Our patients had fewer pretreatment neurological complications (PFP, pareses) than reported for Bannwarth syndrome decades ago, probably as the result of earlier recognition and prompt antibiotic treatment. Unfavorable outcome was rare and was predicted by the continued presence of symptoms 14 days after commencement of treatment.
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Anticorpos Antibacterianos/sangue , Grupo Borrelia Burgdorferi/imunologia , Neuroborreliose de Lyme/diagnóstico , Idoso , Braço/microbiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Perna (Membro)/microbiologia , Neuroborreliose de Lyme/microbiologia , Masculino , Pessoa de Meia-Idade , Pescoço/microbiologia , Tronco/microbiologiaRESUMO
Detection of intrathecally produced specific antibodies (AI) is essential in the diagnosis of Lyme neuroborreliosis (LNB); however, the performance of various newer AI detection methods has not been systematically assessed. Here we assessed and compared advanced test systems for detecting borrelia IgG-AI and IgM-AI. Serum and cerebrospinal fluid (CSF) samples from well-defined LNB and tick-borne encephalitis (TBE) patients, 25 each, were tested with three antibody detection systems, one based on chemiluminescence (CLA) and two based on enzyme-linked immunosorbent assays (ELISA), employing different antigens for detection of IgG and IgM antibodies. In samples from patients with LNB, IgG-AI was detected in 20 samples by CLA, 19 by ELISA1, and 22 by ELISA2, and IgM-AI was detected in 16 samples by CLA, six by ELISA1, and 11 by ELISA2. In samples from TBE patients, IgG-AI was positive in one case by CLA and ELISA2, and in 7 cases by ELISA1, whereas IgM-AI was positive in one case by CLA and in none by ELISA. IgG-AI and IgM-AI were not detected within the first week of disease. Duration of disease correlated with IgG-AI while IgM-AI results were heterogeneous for each test assay. Moreover, the levels of IgG-AI, but not IgM-AI, correlated with protein concentration in CSF. IgG is the relevant immunoglobulin isotype for detecting intrathecal synthesis of borrelia antibodies. The highest sensitivity and specificity were achieved by the antibody detection assay using VlsE IR6 peptide. Detection of IgM-AI yielded heterogenous results and did not support the laboratory diagnosis of LNB.
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Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Bactérias/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Lipoproteínas/imunologia , Neuroborreliose de Lyme/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/líquido cefalorraquidiano , Anticorpos Antibacterianos/imunologia , Extratos Celulares/imunologia , Encefalite Transmitida por Carrapatos/sangue , Encefalite Transmitida por Carrapatos/líquido cefalorraquidiano , Encefalite Transmitida por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/microbiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina M/sangue , Imunoglobulina M/líquido cefalorraquidiano , Neuroborreliose de Lyme/microbiologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/imunologia , Adulto JovemRESUMO
Although two-tier testing is standard practice in both the United States and Europe for the serologic diagnosis of Lyme borreliosis (LB), the test kits generally differ. The purpose of this study was to determine if the testing used in the United States will detect LB acquired in Europe and vice versa. Testing was performed on a convenience sample of archived sera from 40 LB patients from Austria and 39 from the United States, using first- and second-tier test kits from both the United States and Europe. The sensitivity of four first-tier tests from Europe and two first-tier tests from the United States was similar. Thus, two-tier testing was compared to the C6 ELISA as the first-tier test, since it is licensed in both the United States and Europe. The sensitivity of C6 two-tier testing with US assays was 9/40 (22.5 % [95 % CI 10.8-38.5 %]) for detection of LB acquired in Europe, and just 20.0 % (95 % CI 2.5-55.6 %) in the ten European patients with neurologic involvement. These results differed significantly from the sensitivity of European C6 two-tier testing that was 70.0 % (95 % CI 53.5-83.4 %) overall (p < 0.001) and 90.0 % (95 % CI 55.5-99.7 %) for the European patients with neurologic manifestations specifically (p = 0.016). In contrast, the sensitivity of European and US C6 two-tier testing was similar for detection of LB acquired in the United States. Two-tier serologic testing with the US test kits may be unsatisfactory for detection of LB acquired in Europe. First-tier testing with an assay such as the C6 ELISA should be considered as a stand-alone diagnostic strategy in such cases.
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Doença de Lyme/diagnóstico , Testes Sorológicos , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Borrelia burgdorferi/imunologia , Ensaio de Imunoadsorção Enzimática , Europa (Continente) , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Doença de Lyme/imunologia , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Testes Sorológicos/normas , Estados UnidosRESUMO
Information on asplenic Lyme borreliosis (LB) patients with erythema migrans (EM) is lacking. We compared the course and outcome of 26 EM episodes in 24 post-trauma splenectomized patients (median age 51 years) diagnosed at a single clinical center in Slovenia during 1994-2023 with those of 52 age- and sex-matched patients with EM but with no history of splenectomy. All patients were followed for one year. A comparison of pre-treatment characteristics revealed that EM in splenectomized patients was of shorter duration before diagnosis (4 vs. 8 days, p = 0.034) with a smaller EM diameter (10.5 vs. 14 cm, p = 0.046), and more frequently fulfilled criteria for disseminated LB (3/26, 11.5% vs. 0%, p = 0.034). Treatment failure occurred in 5/26 (19.2%) EM episodes in splenectomized patients versus 0/52 in non-splenectomized patients (p = 0.003). The five treatment failure cases were retreated with antibiotic regimens used to treat EM and had complete resolution of all symptoms/signs. In conclusion, our study showed that splenectomized adult patients with EM differ somewhat in presentation and more often have treatment failure compared with non-splenectomized patients with EM.
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Erythema migrans (EM) is the initial and the most frequent clinical manifestation of Lyme borreliosis (LB). Herein, we report on the capacity of culture and serology for the demonstration of Borrelia infection in a cohort of 292 patients diagnosed with typical EM at a single medical center. The median duration of EM at diagnosis was 12 days, and the largest diameter was 16 cm; 252 (86.3%) patients presented with solitary EM, whereas 40 (13.7%) had multiple EM. A total of 95/292 (32.5%) patients had positive IgM, and 169 (57.9%) had positive IgG serum antibodies; the Borrelia isolation rate was 182/292 (62.3%). The most frequent species by far was B. afzelii (142/148, 95.9%) while B. garinii (2.7%) and B. burgdorferi s.s. (1.4%) were rare. IgM seropositivity was associated with a younger age, multiple EM and the absence of underlying chronic illness; IgG seropositivity was associated with the duration of EM at diagnosis, the diameter of the EM, having had a previous episode of LB and the absence of symptoms at the site of the EM. Furthermore, the Borrelia isolation rate was statistically significantly lower in patients with positive Borrelia IgM antibodies. Although microbiologic analyses are not needed for the diagnosis of typical EM, they enable insights into the etiology and dynamics of the immune response in the course of early LB.
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In prior studies, the skin lesion erythema migrans (EM) was present for a longer time period before diagnosis of concomitant borrelial meningoradiculoneuritis (Bannwarth's syndrome) compared to EM patients without neurologic symptoms. To determine if this observation pertains to other manifestations of Lyme neuroborreliosis (LNB), we compared EM characteristics in patients with borrelial meningoradiculoneuritis (n = 122) to those with aseptic meningitis without radicular pain (n = 72 patients), and to patients with EM but without neurologic involvement (n = 12,384). We also assessed factors that might impact duration. We found that the duration of EM at diagnosis in patients with borrelial meningoradiculoneuritis was not significantly different compared with those with LNB without radicular pain (34 vs. 26 days; p = 0.227). The duration of EM for each of these clinical presentations of LNB, however, was significantly longer than in patients with EM without LNB (10 days; p < 0.001). Contributing factors to this difference might have been that patients with LNB failed to recognize that they had EM or were unaware of the importance of not delaying antibiotic treatment for EM. In conclusion, the duration of the EM skin lesion in EM patients with LNB is longer than in patients with just EM, irrespective of the type of LNB.
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PURPOSE: Since some patients with tick-borne encephalitis (TBE) have pronounced myalgias, and since myositis is reported in Flavivirus diseases such as dengue, we performed systematic search for abnormalities of muscle enzymes in a group of patients in whom the presence of tick-borne encephalitis virus (TBEV) RNA in the first phase of the disease was demonstrated and who developed second phase of TBE. METHODS: Total leukocyte and platelet blood counts were determined routinely at the initial examination during the first and the second phase of TBE. Activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), myoglobin and troponin was determined from the available stored serum specimens; the first and second phase disease specimens were tested simultaneously. RESULTS: Of 24 patients with biphasic course of TBE, 83% had leukopenia, 65% thrombocytopenia, 83% elevated AST and 4% elevated ALT level. Furthermore, 33% had elevated serum CK, 26% myoglobin and 22% troponin activity; at least one of the muscle enzymes was elevated in 42% of patients. Leukopenia, thrombocytopenia, elevated liver enzymes and elevations of CK and myoglobin were present in the initial phase but resolve later, while troponin abnormalities were also found in the second phase of TBE. CONCLUSIONS: The present study exposes that in addition to previously known leukopenia, thrombocytopenia and increased liver enzymes activity, the initial phase of TBE is relatively often associated also with elevated muscle enzymes. Clinical relevance of these findings remains to be determined.
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BACKGROUND: Our objective was to obtain data on patients with erythema migrans (EM) who have symptoms/signs suggesting nervous system involvement and to compare epidemiologic, clinical, and microbiologic findings in patients with and without cerebrospinal fluid (CSF) pleocytosis. METHODS: Adult patients with EM and suspected early Lyme neuroborreliosis were included in this study. RESULTS: Of 161 patients, 31 (19%) had elevated and 130 (81%) had normal CSF cell counts. In contrast to patients with normal CSF cell counts, those with pleocytosis (1) more often reported radicular pain and more often presented with meningeal signs but less frequently complained of malaise; (2) had larger EM skin lesions despite similar duration; (3) more commonly had Borrelia garinii isolated from EM skin lesions (odds ratio for pleocytosis was 31 times higher in patients with established B. garinii skin infection compared to patients with other Borrelia species isolated from their EM skin lesion) and from CSF; and (4) more frequently fulfilled microbiologic criteria for established borrelial infection of the central nervous system. The positive predictive value of pleocytosis for microbiologically proven borrelial infection of the central nervous system (defined by isolation of Borrelia from CSF and/or demonstration of intrathecal synthesis of borrelial antibodies) was 67.9%, whereas normal CSF white cell counts ruled out Lyme neuroborreliosis with a predictive value of 91.9%. CONCLUSIONS: Comparison of European patients with EM who had symptoms/signs suggesting early Lyme neuroborreliosis revealed several differences in the clinical presentation and in microbiologic test results according to CSF findings.
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Borrelia/isolamento & purificação , Glossite Migratória Benigna/diagnóstico , Glossite Migratória Benigna/patologia , Neuroborreliose de Lyme/diagnóstico , Neuroborreliose de Lyme/patologia , Adulto , Idoso , Borrelia/classificação , Líquido Cefalorraquidiano/citologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Lyme disease is the most common vector-borne disease in North America and Europe. The clinical manifestations of Lyme disease vary based on the genospecies of the infecting Borrelia burgdorferi spirochete, but the microbial genetic elements underlying these associations are not known. Here, we report the whole genome sequence (WGS) and analysis of 299 patient-derived B. burgdorferi sensu stricto ( Bbss ) isolates from patients in the Eastern and Midwestern US and Central Europe. We develop a WGS-based classification of Bbss isolates, confirm and extend the findings of previous single- and multi-locus typing systems, define the plasmid profiles of human-infectious Bbss isolates, annotate the core and strain-variable surface lipoproteome, and identify loci associated with disseminated infection. A core genome consisting of âË»800 open reading frames and a core set of plasmids consisting of lp17, lp25, lp36, lp28-3, lp28-4, lp54, and cp26 are found in nearly all isolates. Strain-variable (accessory) plasmids and genes correlate strongly with phylogeny. Using genetic association study methods, we identify an accessory genome signature associated with dissemination and define the individual plasmids and genes that make up this signature. Strains within the RST1/WGS A subgroup, particularly a subset marked by the OspC type A genotype, are associated with increased rates of dissemination. OspC type A strains possess a unique constellation of strongly linked genetic changes including the presence of lp56 and lp28-1 plasmids and a cluster of genes that may contribute to their enhanced virulence compared to other genotypes. The patterns of OspC type A strains typify a broader paradigm across Bbss isolates, in which genetic structure is defined by correlated groups of strain-variable genes located predominantly on plasmids, particularly for expression of surface-exposed lipoproteins. These clusters of genes are inherited in blocks through strain-specific patterns of plasmid occupancy and are associated with the probability of invasive infection.
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Tick-borne encephalitis (TBE) usually has a biphasic course which begins with unspecific febrile illness, followed by central nervous system involvement. Because TBE is not yet suspected during the initial phase, knowledge of early TBE pathogenesis is incomplete. Herein we evaluated laboratory and immune findings in the initial and second (meningoencephalitic) phase of TBE in 88 well-defined adult patients. Comparison of nine laboratory blood parameters in both phases of TBE revealed that laboratory abnormalities, consisting of low leukocyte and platelet counts and increased liver enzymes levels, were predominately associated with the initial phase of TBE and resolved thereafter. Assessment of 29 immune mediators in serum during the initial phase, and in serum and cerebrospinal fluid (CSF) during the second phase of TBE revealed highly distinct clustering patterns among the three groups. In the initial phase of TBE, the primary finding in serum was a rather heterogeneous immune response involving innate (CXCL11), B cell (CXCL13, BAFF), and T cell mediators (IL-27 and IL-4). During the second phase of TBE, growth factors associated with angiogenesis (GRO-α and VEGF-A) were the predominant characteristic in serum, whereas innate and Th1 mediators were the defining feature of immune responses in CSF. These findings imply that distinct immune processes play a role in the pathophysiology of different phases of TBE and in different compartments.
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Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Meningoencefalite , Adulto , Linfócitos B , HumanosRESUMO
To assess whether differences in presentation between US and European patients with early Lyme borreliosis are due to the lower rate of spirochetemia in Europe, we compared multiple variables for patients with erythema migrans (EM), restricting the analysis to subjects with a positive blood culture at the time of presentation: 93 US patients infected with Borrelia burgdorferi versus 183 European patients infected with Borrelia afzelii (No = 144) or Borrelia garinii (No = 39). Compared to spirochetemic Slovenian EM patients infected with B. afzelii, US patients with a positive blood culture significantly less often recalled a preceding tick bite at the site of the EM skin lesion, had a shorter duration of EM prior to diagnosis and more often had multiple EM lesions, regional lymphadenopathy, constitutional symptoms, an increased ESR value, a low blood lymphocyte count and detectable borrelia antibodies in acute and convalescent phase blood samples. Similar differences were observed when US patients were compared to Slovenian patients with B. garinii infection, but not all reached statistical significance. The findings are comparable to those previously reported for the corresponding skin culture positive patients and do not support the hypothesis that a higher frequency of spirochetemia at the time of presentation in US patients with EM, compared with European EM patients, is the reason for the observed differences.
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Neither pre-treatment characteristics, nor the outcome after antibiotic therapy, have been reported for spirochetemic European patients with Lyme borreliosis. In the present study, patients with a solitary erythema migrans (EM) who had a positive blood culture for either Borrelia afzelii (n = 116) or Borrelia garinii (n = 37) were compared with age- and sex-matched patients who had a negative blood culture, but were culture positive for the corresponding Borrelia species from skin. Collectively, spirochetemic patients significantly more often recalled a tick bite at the site of the EM skin lesion, had a shorter time interval from the bite to the onset of EM, had a shorter duration of the skin lesion prior to diagnosis, and had a smaller EM skin lesion that was more often homogeneous in appearance. Similar results were found for the subset of spirochetemic patients infected with B. afzelii but not for those infected with B. garinii. However, patients with B. garinii bacteremia had faster-spreading and larger EM skin lesions, and more often reported itching at the site of the lesion than patients with B. afzelii bacteremia. Treatment failures were rare (7/306 patients, 2.3%) and were not associated with having spirochetemia or with which Borrelia species was causing the infection.
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Antibacterianos/uso terapêutico , Eritema Migrans Crônico/diagnóstico , Doença de Lyme/diagnóstico , Pele/patologia , Adulto , Eritema Migrans Crônico/tratamento farmacológico , Eritema Migrans Crônico/patologia , Europa (Continente) , Feminino , Humanos , Doença de Lyme/tratamento farmacológico , Doença de Lyme/patologia , Masculino , Pessoa de Meia-Idade , Picadas de Carrapatos , Resultado do TratamentoRESUMO
Statins have anti-inflammatory and potentially antimicrobial activity, but whether they have a beneficial effect on the course of infectious diseases is controversial. In this study, we assessed the impact of pre-existing statin use on the course and outcome of Lyme neuroborreliosis manifested as meningoradiculitis (Bannwarth's syndrome). One hundred and twenty three consecutive patients with Bannwarth's syndrome, of whom 18 (14.6%) were being treated with statins, were included in the study. To assess the influence of statin use on the course and outcome of the disease, univariate and multivariable analyses were performed. No statistically significant association was found between statin pre-treatment and the clinical manifestations, laboratory test results, and outcome of Bannwarth's syndrome. In conclusion, pre-existing use of statins did not significantly impact either the clinical presentation or the outcome of Bannwarth's syndrome.
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The study evaluated the course and outcome of erythema migrans in patients receiving tumour necrosis factor-alpha (TNF-α) inhibitors. Among 4157 adults diagnosed with erythema migrans in the period 2009-2018, 16 (2.6%) patients were receiving TNF-α inhibitors (adalimumab, infliximab, etarnecept, golimumab), often in combination with other immunosuppressants, for rheumatic (13 patients) or inflammatory bowel (three patients) disease. Findings in this group were compared with those in 32 sex- and age-matched immunocompetent patients diagnosed with erythema migrans in the same years. In comparison with the control group, the immunocompromised patients had a shorter incubation period (7 vs. 14 days; p = 0.0153), smaller diameter of erythema migrans (10.5 vs. 15.5 cm; p = 0.0014), and more frequent comorbidities other than immune-mediated diseases (62.5% vs. 25%, p = 0.0269), symptoms/signs of disseminated Lyme borreliosis (18.8% vs. 0%, p = 0.0324), and treatment failure (25% vs. 0%, p = 0.0094). After retreatment with an antibiotic, the clinical course of Lyme borreliosis resolved. Continuing TNF inhibitor treatment during concomitant borrelial infection while using identical approaches for antibiotic treatment as in immunocompetent patients resulted in more frequent failure of erythema migrans treatment in patients receiving TNF inhibitors. However, the majority of treatment failures were mild, and the course and outcome of Lyme borreliosis after retreatment with antibiotics was favourable.