Associations of the cerebrospinal fluid lymphocyte population with a clinical presentation of tick-borne encephalitis.

In tick-borne encephalitis (TBE), lymphocytes infiltrating central nervous system are indispensable for the infection control, but also potentially immunopathogenic. To clarify their roles, we have evaluated cerebrospinal fluid (CSF) count of the main lymphocyte populations (considered as a proxy of the brain parenchyma lymphocytic infiltrate) in TBE patients and analyzed if they associate with clinical presentation, blood-brain barrier disruption and intrathecal antibody synthesis. We have studied CSF from 96 adults with TBE (50 with meningitis, 40 with meningoencephalitis, 6 with meningoencephalomyelitis), 17 children and adolescents with TBE and 27 adults with non-TBE lymphocytic meningitis. Th CD3+CD4+, Tc CD3+CD8+, double positive T CD3+CD4+CD8+, B CD19+ and NK CD16+/56+ cells were counted cytometrically with a commercial fluorochrome-stained monoclonal antibody set. The associations between the counts and fractions of these cells and clinical parameters were analyzed with non-parametric tests, p<0.05 considered significant. The TBE patients had lower pleocytosis with similar proportions of the lymphocyte populations compared to non-TBE meningitis. The different lymphocyte populations correlated positively with one another, as well as with CSF albumin, IgG and IgM quotients. The higher pleocytosis and expansion of Th, Tc and B cells associated with a more severe disease and neurologic involvement: Th with encephalopathy, myelitis and weakly with cerebellar syndrome, Tc with myelitis and weakly with encephalopathy, B with myelitis and with at least moderately severe encephalopathy. The double-positive T lymphocytes associated with myelitis, but not with other forms of CNS involvement. The fraction of double positive T cells decreased in encephalopathy and the fraction of NK in patients with neurologic deficits. In children with TBE, Tc and B counts were increased at the expense of Th lymphocytes in comparison with adults. The concerted intrathecal immune response, involving the main lymphocyte populations, increases with the clinical severity of TBE, with no evidently protective or pathogenic elements distinguishable. However, the particular populations including B, Th and Tc cells associate with different, though overlapping, spectra of CNS manifestations, suggesting they may be specifically related to TBE manifesting as myelitis, encephalopathy and cerebellitis. The double-positive T and NK cells do not expand evidently with severity and may be most closely associated with the protective anti-TBEV response.

The Detectability of the Viral RNA in Blood and Cerebrospinal Fluid of Patients with Tick-Borne Encephalitis.

BACKGROUND: The detection rate of viral RNA in tick-borne encephalitis (TBE) is low and variable between studies, and its diagnostic/prognostic potential is not well defined. We attempted to detect RNA of TBE virus (TBEV) in body fluids of TBE patients. METHODS: We studied 98 adults and 12 children with TBEV infection, stratified by the disease phase and presentation. EDTA blood and cerebrospinal fluid (CSF) samples were obtained upon hospital admission. RNA was extracted from freshly obtained plasma, concentrated leukocyte-enriched CSF, and whole blood samples, and real time PCR was performed with a Rotor-Gene Q thermocycler. RESULTS: TBEV RNA was detected in (1) plasma of one (of the two studied) adult patients with an abortive infection, (2) plasma of two (of the two studied) adults in the peripheral phase of TBE, and (3) plasma and blood of an adult in the neurologic phase of TBE presenting as meningoencephalomyelitis. No CSF samples were TBEV RNA-positive. CONCLUSIONS: The detection of TBEV RNA in blood might be diagnostic in the peripheral phase of TBE. The lack of TBEV RNA in the CSF cellular fraction speaks against TBEV influx into the central nervous system with infiltrating leukocytes and is consistent with a relatively low intrathecal viral burden.

The Prevalence of Asymptomatic Infections with Tick-Borne Encephalitis Virus and Attitude towards Tick-Borne Encephalitis Vaccine in the Endemic Area of Northeastern Poland.

In Poland, tick-borne encephalitis (TBE) vaccination rate is low despite high incidence of severe infections with TBE virus (TBEV). However, infection with TBEV can be asymptomatic or mild, which makes the total number of cases difficult to assess. We aimed at assessing asymptomatic TBEV infections and describing attitudes towards the TBE vaccine. We studied 298 healthy adult blood donors and 180 children from the TBE endemic area of northeastern Poland for the presence of anti-TBEV IgG antibodies. We also surveyed a separate cohort of 444 adults. Thirty-eight blood donors (13%) and 38 survey respondents (9%) reported a history of a prior anti-TBEV vaccination. Forty respondents (9%) reported vaccinating their child in the past. Fourteen unvaccinated blood donors (5%) and four children (2%) were seropositive for specific anti-TBEV antibodies, suggesting a history of an undiagnosed TBEV infection. In the surveyed cohort, 130 (32%) expressed their intention to be vaccinated and 144 (36%) expressed their intention to vaccinate their child. This intention was significantly higher in respondents with a recent tick-bite, a diagnosis of tick-borne disease in a close relative, and in males. Our study shows that asymptomatic TBEV infections are common. The acceptance of TBE vaccine is low, but might be increased by communicating risks associated with tick bites.

Analysis of Clinical Course and Vaccination Influence on Serological Response in COVID-19 Convalescents.

Our goal was to assess the anti-SARS-CoV-2 antibodies presence in COVID-19 convalescents and assess the differences in anti-SARS-CoV-2 antibodies production regarding the disease severity, sex, vaccination, and assess the correlation between anti-SARS-CoV-2 antibodies production and inflammatory parameters. Three hundred twenty-two COVID-19 patients (282 hospitalized and 40 patients with oligosymptomatic COVID-19 isolated at homes) were included in the study. Blood was taken at 4 time points: during hospitalization, 1 month, 3 months, and 6 months. Detection of SARS-CoV-2 antibodies was performed with LIAISON SARS-CoV-2 S1/S2 IgG tests (DiaSorin, Italy). Clinical and laboratory parameters were compared. Significant differences between higher anti-SARS-CoV-2 antibodies titer in symptomatic patients 3 months after infection (III sample) and significantly higher ratio II/I in symptomatic patients were observed. Subgroup analysis based on sex showed differences only in laboratory tests, not in serological. Analysis of the results of serological tests showed significant differences in ratio IV/I and a significant increase in antibodies level after vaccination. The most significant rise was observed between the 3rd and 6th month when the patients received a vaccination. Immunological response after COVID-19 infection lasted over 6 months in all patients, although antibodies titers were significantly higher in patients with a history of severe COVID-19 and vaccinated patients. Immunological response after COVID-19 infection did not depend on sex. There was a significant correlation between anti-SARS-CoV-2 antibodies production and the degree of inflammation in the acute phase of the disease (inflammatory parameters in blood and severity of lung affection in CT). IMPORTANCE The results of our study confirm the knowledge on immune response in the Polish population and add new information regarding correlations with the severity of the disease. The data in the literature concerning the correlation between antibodies response and sex are ambiguous, and we did not observe differences between antibodies production and gender, which also adds new information.

Anti-TBE Intrathecal Synthesis as a Prediction Marker in TBE Patients.

Tick-borne encephalitis (TBE) is an emerging vector-borne disease in Europe caused by tick-borne encephalitis virus (TBEV), which belongs to Flaviviridae. Although most of the patients quickly recover from TBE, some require further neurological and psychiatric treatment due to persistent symptoms. The aim of the study was to evaluate the usefulness of an antibodies index for predicting the course of the disease and potential persistent sequalae. Sixty-six patients (49 males and 17 females, mean age 45.97 ± 13.69 years) with TBE hospitalized in the Department of Infectious Diseases and Neuroinfections, Medical University of Bialystok, Poland, in years 2016-2019 were included to the study. TBE antibodies titer in serum and CSF samples were measured with an Anti-TBEV ELISA (IgM, IgG) EUROIMMUN test. Patients who developed persistent sequelae after TBE had significantly lower IgG intrathecal index at admission. Additionally, IgG2/IgG1was significantly higher in patients who developed sequelae. IgG intrathecal index might be a useful tool for the prediction of TBE sequelae development.

The Lack of the Association of the CCR5 Genotype with the Clinical Presentation and Frequency of Tick-Borne Encephalitis in the Polish Population.

BACKGROUND: The host factors influencing the susceptibility to and the severity of tick-borne encephalitis (TBE) are poorly defined. The loss-of-function Δ32 mutation in the chemokine receptor gene CCR5 was identified as a risk factor for West Nile encephalitis and possibly for TBE, suggesting a protective role of CCR5 in Flavivirus encephalitis. METHODS: We studied the CCR5 genotype in 205 TBE patients stratified by a clinical presentation and 257 controls from the same endemic area (Podlasie, Poland). The genotype distribution between the groups and differences between TBE patients with different genotypes were analyzed. RESULTS: There were 36 (17.6%) CCR5Δ32 heterozygotes and 3 (1.5%) homozygotes in the TBE group, with no statistically significant difference in comparison with the controls. The CCR5Δ32 allele did not associate with the clinical presentation or the severity of TBE. The cerebrospinal fluid (CSF) inflammatory parameters did not differ between the wild-type (wt/wt) and wt/Δ32 genotype patients. The TBE clinical presentation and CSF parameters in three Δ32/Δ32 homozygotes were unremarkable. CONCLUSIONS: The lack of association of CCR5Δ32 with the risk and clinical presentation of TBE challenges the suspected CCR5 protective role. CCR5 is not indispensable for the effective immune response against the TBE virus.

Assessment of the YKL-40 concentration in patients with tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a viral infection of the central nervous system (CNS) caused by tick-borne encephalitis virus (TBEV). It might take several clinical courses such as: meningitis, meningoencephalitis or meningoencephalomyelitis. The aim this study was to compare the YKL-40 concentration in cerebrospinal fluid (CSF) of patients with different clinical presentations of TBE and patients with excluded meningitis (control group). The concentration of YKL-40 in CSF was determined using Fujirebio tests (Ghent, Belgium) in 32 patients with TBE: Group I-patients with meningoencephalitis (n = 16); Group II-patients with meningitis (n = 16). The control group (CG) consisted of 17 patients in whom any inflammatory process in central nervous system was excluded. The concentration of YKL-40 was significantly higher in encephalitis group than in the CG after 7 days from the last dose of treatment. The concentration in patients with neuroinflammation had a significantly different concentration of YKL-40 compared to patients from the neuroinflammation control group. The ROC curve analysis indicates that CSF YKL-40 concentration at cut-off 783.87 differentiated TBE patients from CG with 100% specificity and 70% sensitivity and CSF YKL-40 concentration at cut-off 980.11 differentiated meningitis from meningoencephalitis with 87.5% specificity and 62.5% sensitivity. YKL-40 takes part in TBE pathogenesis, its concentration is the highest at the early stage of CNS involvement and decreases in the convalescent period. As YKL-40 was significantly higher in the meningitis than in the meningoencephalitis group, it might be used as biomarker in differentiation of these clinical forms of TBE.

Epidemiology of tick-borne encephalitis in Poland (2010-2019) and the impact of the COVID-19 pandemic on the notified incidence of the disease.

INTRODUCTION: Tick-borne encephalitis (TBE) is endemic in many parts of Eurasia including countries previously considered to be free from the disease. The incidence of TBE is changing owing to various ecological and climatic factors. The factors influencing the variability of the number of TBE cases are still under investigation. In 2020 the new coronavirus SARS-CoV-2 emerged causing COVID-19 pandemic. Governments have reorganized health care systems to contain a surge of COVID-19 cases and avoid hospital overload. Moreover, new measures have modified several aspects of social habits leading to a change in the incidence of numerous diseases. We aimed to evaluate the epidemiology of TBE in the last decade (2010-2019) and to demonstrate the impact of the surge of SARS-CoV-2 infections on the TBE incidence as reported to a national surveillance database. MATERIAL AND METHODS: We performed the analysis of the TBE notification from the epidemiologic reports in the years 2010-2019 and in the pandemic year 2020 at a national and regional level in Poland. We included data from two infectious disease departments located in the most TBE-prevalent province of Poland. RESULTS: Most cases of TBE occur in two provinces of Northeastern Poland from May to December. The increasing temporal trend occurred in Poland in 2016-2017. The increased number of cases of COVID-19 coincided with a reduction of the number of the reported TBE cases in 2020. CONCLUSIONS: Tick-borne encephalitis virus activity in Poland is invariably concentrated in endemic regions of Northeastern Poland fluctuating considerably from year to year. The decrease of TBE incidence with surge of COVID-19 patients conceivably resulted from underreporting due to limited access to specialized diagnostics. In endemic areas, TBE should be included in the differential diagnostics in all the cases when the central nervous system infection in suspected.

Anaplasmosis in Poland - analysis of 120 patients.

The aim of our study was to clarify the clinical picture of anaplasmosis through analysis of the symptoms and clinical signs presented by infected patients in a cohort of tick-bitten individuals. The study included 1375 patients with suspicion of tick-borne disease. Finally, 120 patients (8.7%) were diagnosed with anaplasmosis (HGA). Blood samples were examined by PCR for Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis, Borrelia burgdorferi sensu lato, Babesia spp., and Bartonella spp.. Based on analysis of 120 patients with HGA we concluded that anaplasmosis is not as rare in Europe, as it is thought to be and often appears as a co-infection with other tick-borne pathogens. The co-infection rate of patients with A. phagocytophilum infection in tick endemic areas is high. Co-infection of A. phagocytophilum with B. burgdorferi s.l. or tick-borne encephalitis virus may influence symptom frequency. PCR together with medical history, clinical picture and basic laboratory tests is a sufficient method for the diagnosis of anaplasmosis. Doxycycline is an effective drug leading to complete recovery.

The increased intrathecal expression of the monocyte-attracting chemokines CCL7 and CXCL12 in tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a relatively severe and clinically variable central nervous system (CNS) disease with a significant contribution of a secondary immunopathology. Monocytes/macrophages play an important role in the CNS inflammation, but their pathogenetic role and migration mechanisms in flavivirus encephalitis in humans are not well known. We have retrospectively analyzed blood and cerebrospinal fluid (CSF) monocyte counts in 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114), or meningoencephalomyelitis (n = 16), searching for associations with other laboratory parameters, clinical presentation, and severity. We have measured concentrations of selected monocytes-attracting chemokines (CCL7, CXCL12, CCL20) in serum and CSF of the prospectively recruited patients with TBE (n = 15), with non-TBE aseptic meningitis (n = 6) and in non-infected controls (n = 8). The data were analyzed with non-parametric tests, p < 0.05 considered significant. Monocyte CSF count correlated with other CSF inflammatory parameters, but not with the peripheral monocytosis, consistent with an active recruitment into CNS. The monocyte count did not correlate with a clinical presentation. The median CSF concentration of CCL7 and CXCL12 was increased in TBE, and that of CCL7 was higher in TBE than in non-TBE meningitis. The comparison of serum and CSF concentrations pointed to the intrathecal synthesis of CCL7 and CXCL12, but with no evident concentration gradients toward CSF. In conclusion, the monocytes are recruited into the intrathecal compartment in concert with other leukocyte populations in TBE. CCL7 and CXCL12 have been found upregulated intrathecally but are not likely to be the main monocyte chemoattractants.

The chemotactic cytokines in the cerebrospinal fluid of patients with neuroborreliosis.

BACKGROUND: The outcome of neuroborreliosis (NB) is variable and may partially depend on host-related immune factors. In NB, the cerebrospinal fluid (CSF) contains a large population of T lymphocytes, but the mechanisms and consequences of their recruitment have not been fully elucidated. We have studied expression of T lymphocyte chemoattractant cytokines in association with CSF cytometric parameters and clinical data in NB patients. METHODS: The blood and CSF of 17 patients with NB and blood of 12 patients with erythema migrans (EM) were obtained before the antibiotic administration, and in fraction of NB patients during and/or after antibiotic treatment. The control samples came from blood donors (blood) and patients in whom neuroinfection was excluded by a lumbar puncture (CSF). Concentrations of IL-16, CXCL9, CXCL10, CXCL11, CCL2 and CCL5 in serum and CSF were measured with commercial ELISA. Data were analyzed with non-parametric tests, p < 0.05 considered significant. RESULTS: The serum concentrations of IL-16, CXCL9, CXCL10 and CCL5 were increased, higher in NB than in EM. In CSF all the cytokines were upregulated, CXCL10, CXCL9 and IL-16 over ten-fold. The CSF concentration index favored the intrathecal synthesis of all the cytokines except CCL5, for which it could not be reliably estimated. CCL2, CXCL10 and CXCL9 created concentration gradients towards CSF. The intrathecal expression of IL-16, CCL5 and CXCL9 correlated with CSF lymphocyte counts, of IL-16, CXCL9 and CXCL10 - with a blood-brain barrier disruption, and of CXCL9 and CXCL10 with intrathecal specific IgG synthesis. The expression of CCL2, CXCL10 and CXCL11 peaked early after NB onset and decreased naturally afterwards. High initial CSF CXCL9, CXCL10 and CXCL11 levels associated with a persistent CSF pleocytosis and BBB disruption after treatment, but no cytokine was predictive of clinical outcome. In follow up (post-treatment) examinations, CSF CXCL10 and CCL5 associated positively and CCL2 negatively with a protracted lymphocytic pleocytosis. CONCLUSIONS: Several cytokines chemotactic for T lymphocytes are upregulated intrathecally in NB, with different dynamics and relation to other inflammatory parameters, suggesting their distinct pathogenetic roles. CXCL10 and CXCL9 are vividly upregulated and seem deeply involved in the pathogenesis of the intrathecal inflammation. IL-16 and CCL5 may directly drive T lymphocyte migration from periphery, but their ability to create an adequate chemotactic gradient remains to be confirmed. A delayed normalization of pleocytosis is accompanied by higher intrathecal expression of Th1-related and lower of Th2-related chemokines, in agreement with the protective role of Th1 to Th2 transition in the course of NB.

The lymphocyte populations and their migration into the central nervous system in tick-borne encephalitis.

In tick-borne encephalitis (TBE) the cerebrospinal fluid (CSF) cytosis is dominated by T CD3+CD4+ and T CD3+CD8+ lymphocytes, but their pathogenetic roles and mechanisms of migration into central nervous system (CNS) are unclear. Currently, we have studied CSF lymphocyte subsets and chemotactic axes in TBE patients stratified according to the clinical presentation. Blood and CSF were obtained from 51 patients with TBE (presenting as meningitis in 30, meningoencephalitis in 18 and meningoencephalomyelitis in 3), 20 with non-TBE meningitis and 11 healthy controls. We have studied: (1) abundances of the main lymphocyte subsets and (2) CXCR3 and CCR5 expression on CD3+CD4+ and CD3+CD8+ lymphocytes cytometrically with fluorochrome-stained monoclonal antibodies; (3) concentrations of chemotactic cytokines: CCL5 (CCR5 ligand), CXCL10 (CXCR3 ligand), IL-16, CCL2, CCL20 and CXCL5 with ELISA. Cytokine concentrations were additionally studied in 8 pediatric TBE patients. Data were analyzed with non-parametric tests, p < 0.05 considered significant. The higher CSF lymphocyte counts were associated with symptoms of CNS involvement, especially with altered consciousness (B, Th and Tc cells) and focal neurologic deficits (B cells). The minor fraction of double-positive T CD4+CD8+ cells was unique in associating negatively with encephalitis and altered consciousness. CSF CD3+CD4+ and CD3+CD8+ lymphocyte population was enriched in CCR5-positive cells and CCL5 concentration in CSF was increased and associated with a milder presentation. Although CXCL10 was vividly up-regulated intrathecally and correlated with CSF T lymphocyte counts, the CXCR3 expression in CSF T lymphocytes was low. Serum and CSF concentrations of CCL2, CXCL5 and IL-16 were increased in adult TBE patients, CCL2 created a chemotactic gradient towards CSF and both CCL2 and IL-16 concentrations correlated positively with CSF lymphocyte counts. The particular lymphoid cell populations in CSF associate differently with the clinical presentation of TBE, suggesting their distinct roles in pathogenesis. CCR5/CCL5 axis probably contributes to T lymphocyte migration into CNS. CXCL10 mediates the intrathecal immune response, but is probably not directly responsible for T cell migration. Additional chemotactic factors must be involved, probably including CCL2 and IL-16.

Comparison of tick-borne pathogen prevalence in Ixodes ricinus ticks collected in urban areas of Europe.

Tick-borne diseases are a major threat to human and animal health. An increasing number of natural habitats have been transformed into urban areas by human activity; hence, the number of reported tick bites in urban and suburban areas has risen. This retrospective analysis evaluated 53 scientific reports concerning infections of Ixodes ricinus ticks collected from urban and suburban areas of Europe between 1991 and 2017. The results indicate significant differences in many variables, including a higher number of Anaplasma phagocytophilum infections in Eastern Europe than in Western Europe. The opposite result was observed for Candidatus Neoehrlichia mikurensis infections. A comparison of climate zones revealed that Borrelia burgdorferi s.l. infections have the greatest median incidence rate in subtropical climate zones. No statistical significance was found when comparing other tick-borne pathogens (TBPs), such as Borrelia miyamotoi, Rickettsia spp., Babesia spp., Bartonella spp., Ehrlichia spp., Coxiella burnetii and Francisella tularensis. The analysis also showed significant differences in the overall prevalence of TBPs according to average temperatures and rainfall across Europe. This retrospective study contributes to the knowledge on the occurrence and prevalence of TBPs in urbanized areas of Europe and their dependence on the habitats and geographical distributions of ticks. Due to the increased risk of tick bites, it is of great importance to investigate infections in ticks from urban and suburban areas.

Assessment of Anaplasma phagocytophilum presence in early Lyme borreliosis manifested by erythema migrans skin lesions.

BACKGROUND: To investigate to what extent early Lyme borreliosis patients with erythema migrans are infected with Anaplasma phagocytophilum. METHODS: Three hundred ten patients from Poland with erythema migrans were included in the study. One hundred and eighty-three patients (59%) agreed to have both skin biopsy and blood samples analysed for Borrelia burgdorferi, A. phagocytophilum and 'Candidatus Neoehrlichia mikurensis', with PCR. Positive samples were confirmed with sequencing. RESULTS: B. burgdorferi DNA was detected in 49.7% of the skin samples and in 1.1% of the blood samples. A. phagocytophilum DNA was found in 7.1% blood samples, and in 8.2% of the skin biopsies. In four patients, A. phagocytophilum DNA was detected only in blood; in one case A. phagocytophilum DNA was found simultaneously in blood and skin, and additionally in this patients' blood Borrelia DNA was detected. In four skin samples B. burgdorferi DNA was detected simultaneously with A. phagocytophilum DNA, indicative of a co-infection. CONCLUSIONS: A. phagocytophilum may be present in early Lyme borreliosis characterized by erythema migrans and should always be considered as a differential diagnostic following a tick bite and considered in treatment schemes, as these differs (in early stage of Lyme borreliosis doxycycline, amoxicillin, cefuroxime axetil and azithromycin are recommended, while in anaplasmosis the most effective courses of treatment are doxycycline, rifampin and levofloxacin). Consequently, the role of A. phagocytophilum in erythema migrans should be further studied.

Evaluation of cerebrospinal fluid CXCL13 concentrations and lymphocyte subsets in tick-borne encephalitis.

OBJECTIVES: Recent studies suggest that the clinical presentation of tick-borne encephalitis (TBE) is determined by the host immune responses to the tick-borne encephalitis virus (TBEV). The aim of the study was to characterize immune responses in TBE to give a better insight into the immunopathogenesis of this disease. METHODS: Anti-TBEV antibody levels, cerebrospinal fluid (CSF) and blood lymphoid populations, and concentrations of CXCL13 (a potent B-cell and T-cell chemoattractant), were analyzed in 35 patients with TBE (20 adults and 15 children). RESULTS: When compared with the blood, the CSF lymphoid population was significantly enriched in CD4+ T-cells and relatively depleted in natural killer (NK) cells and B lymphocytes. In comparison with TBE meningitis, patients suffering from TBE meningoencephalitis (n = 11, 31%) had a 3.5-fold higher median CSF CXCL13 concentration, 1.8-fold higher CSF/serum ratio of anti-TBEV IgG antibodies, and 1.8-fold higher median CSF cell count. CSF CXCL13 levels did not change significantly in children with TBE meningitis receiving supportive treatment, but decreased in children with TBE meningoencephalitis who received intravenous steroids. CONCLUSIONS: CD4+ cells are abundant in the CSF of patients with TBE. CXCL13 may be involved in the neuropathology of TBE by attracting different subsets of lymphocytes to the CSF.

Nocardia farcinica as a cause of chronic meningitis - case report.

BACKGROUND: Nocardiosis is an uncommon disease caused by aerobic gram-positive bacteria Nocardia spp. Although it is usually an opportunistic infection affecting immunocompromised patients, even one third of cases occur in immunocompetent persons. The aim of the study was to describe the course of chronic meningitis due to Nocardia infection. CASE PRESENTATION: A 52-year-old patient, chalk miner, suffered from a chronic meningitis caused by an extremely rare pathogen. The patient's history was complicated and diagnostic process covered multiple examinations and consultations. Initially Kocuria rosea was cultured, yet after molecular examination the result was verified to Nocardia farcinica. Targeted antibiotic treatment was implemented, which resulted in gradual improvement of patients condition. A full recovery was achieved after one year antibiotic therapy. CONCLUSIONS: 1.Nocardia farcinica is an uncommon but possible cause of chronic meningitis.2.In the case of a chronic meningitis of unknown origin multiple cerebrospinal fluid cultures should be performed as the identification of pathogen may be crucial for patient's recovery.3.In case of unusual culture, such as Kocuria spp. PCR should be performed.

Analysis of CCL-4, CCL-17, CCL-20 and IL-8 concentrations in the serum of patients with tick-borne encephalitis and anaplasmosis.

PURPOSE: Tick-borne co-infections are a serious epidemiological and clinical problem. Only a few studies aimed to investigate the effect of tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA) co-infection in the course of the inflammatory process and the participation of chemokines in the pathomechanism of these diseases. The aim of the study was to evaluate CCL-4, CCL-17, CCL-20, and IL-8 serum concentrations in patients with HGA, TBE and HGA + TBE co-infection. METHODS: Eighty-seven patients with HGA (n = 20), TBE (n = 49) and HGA + TBE (n = 18) were included to the study. The control group (CG) consisted of 20 healthy people. Concentrations of cytokines were measured in serum using commercial ELISA assays. In patients with TBE and HGA + TBE inflammatory markers were assessed during the acute and convalescent period. The results were analyzed using non-parametric tests with p < 0.05 considered as significant. RESULTS: Before treatment, significantly higher concentrations of IL-8, CCL-4 and CCL-20 were observed in HGA patients. CCL-4 and CCL-20 concentrations were significantly higher in TBE patients compared to CG. Concentrations of IL-8, CCL-4, and CCL-20 were significantly higher in HGA + TBE than in CG. After treatment, a significant reduction of IL-8, CCL-4, and CCL-20 concentrations in TBE patients and IL-8 in HGA + TBE co-infection was observed. CCL-4 concentration was higher in HGA + TBE co-infection in comparison to patients with TBE after treatment. CONCLUSIONS: Our study confirms that concentrations of IL-8, CCL-4, and CCL-20 are increased in the course of HGA and TBE. Their concentrations in serum may be used to monitor the course of TBE and HGA, as well as possibly detect co-infections with the diseases.

Assessment of the tau protein concentration in patients with tick-borne encephalitis.

There have been suggestions that tick-borne encephalitis (TBE) may cause neurodenenerative changes in the brain. The aim of this study was the assessment of the tau protein concentration in cerebrospinal fluid (CSF) of patients with different clinical forms of TBE. The concentration of tau protein in CSF was determined using Fujirebio tests (Ghent, Belgium) in 35 patients with TBE: group I-patients with meningitis (n = 16); group II-patients with meningoencephalitis (n = 19). None of the patients reported any neurodegenerative disorder that could affect the results of the study. The control group (CG) consisted of 10 patients in whom inflammatory process in central nervous system was excluded. Tau protein concentration in CSF before treatment did not differ significantly between the examined groups, while its concentration was significantly higher in encephalitis group than in CG after 14 days of treatment. Significant increase in tau protein concentration after treatment was observed in both examined groups. The comparison between the group of patients who fully recovered and patients who presented with persistent symptoms on discharge showed significant differences in tau protein concentration before and after treatment. ROC curve analysis indicates that CSF tau protein concentration before treatment may predict complicated course of the disease with 90.9% specificity and 80% sensitivity, while after treatment, specificity became 72.7% and 71.4% for sensitivity. Correlation analysis showed that in TBE patients (both meningoencephalitis and meningitis groups), CSF pleocytosis before treatment correlated negatively with tau protein concentration in CSF. (1) Neurodegeneration process is present in TBE encephalitis. (2) Tau protein concentration may be used as a predictor of complicated course of TBE.