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 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.

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.

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.

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.

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.

The intrathecal expression and pathogenetic role of Th17 cytokines and CXCR2-binding chemokines in tick-borne encephalitis.

BACKGROUND: Tick-borne encephalitis (TBE) is a clinically variable but potentially severe Flavivirus infection, with the outcome strongly dependent on secondary immunopathology. Neutrophils are present in cerebrospinal fluid (CSF) of TBE patients, but their pathogenetic role remains unknown. In animal models, neutrophils contributed both to the Flavivirus entry into central nervous system (CNS) and to the control of the encephalitis, which we attempted to evaluate in human TBE. METHODS: We analyzed records of 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114) or meningoencephalomyelitis (n = 16) assessing CSF neutrophil count on admission and at follow-up 2 weeks later, and their associations with other laboratory and clinical parameters. We measured serum and CSF concentrations of Th17-type cytokines (interleukin-17A, IL-17F, IL-22) and chemokines attracting neutrophils (IL-8, CXCL1, CXCL2) in patients with TBE (n = 36 for IL-8, n = 15 for other), with non-TBE aseptic meningitis (n = 6) and in non-meningitis controls (n = 7), using commercial ELISA assays. The results were analyzed with non-parametric tests with p < 0.05 considered as significant. RESULTS: On admission, neutrophils were universally present in CSF constituting 25% (median) of total pleocytosis, but on follow-up, they were absent in most of patients (58%) and scarce (< 10%) in 36%. CSF neutrophil count did not correlate with lymphocyte count and blood-brain barrier integrity, did not differ between meningitis and meningoencephalitis, but was higher in meningoencephalomyelitis patients. Prolonged presence of neutrophils in follow-up CSF was associated with encephalitis and neurologic sequelae. All the studied cytokines were expressed intrathecally, with IL-8 having the highest CSF concentration index. Additionally, IL-17A concentration was significantly increased in serum. IL-17F and CXCL1 CSF concentrations correlated with neutrophil count and CXCL1 concentration was higher in patients with encephalitis. CONCLUSIONS: The neutrophil CNS infiltrate does not correlate directly with TBE severity, but is associated with clinical features like myelitis, possibly being involved in its pathogenesis. Th17 cytokine response is present in TBE, especially intrathecally, and contributes to the CNS neutrophilic inflammation. IL-8 and CXCL1 may be chemokines directly responsible for the neutrophil migration.

Sequelae of tick-borne encephalitis in retrospective analysis of 1072 patients.

Tick-borne encephalitis (TBE) is an emerging vector-borne disease in Europe. The aim of the study was to evaluate sequelae and to analyse the potential risk factors predisposing to sequelae development. We performed a retrospective analysis of medical records of 1072 patients who received a 1-month follow-up appointment after hospital discharge. Medical data, such as patients' age, gender, place of living, subjective complaints, neurological and psychiatric sequelae were evaluated twice: at the moment of discharge and at follow-up visits 1 month after discharge. We observed that sequelae may affect 20.6% of TBE patients. Subjective sequelae were more frequent than subjective complaints during the hospitalisation (P < 0.001), while objective neurological symptoms during the hospitalisation were more pronounced than neurological sequelae (P < 0.001). Patients with meningoencephalomyelitis were predisposed to neurological complications, while subjective symptoms were more common in meningoencephalitis. Independent risk factors for sequelae development were: age and cerebrospinal fluid (CSF) protein concentration. The risk of late neurological complications persisting was increased in patients with higher CSF protein concentration. Based on the results of our study we concluded that, there is a need for a better vaccination program, which would prevent the development of sequelae.

Acrodermatitis chronica atrophicans: various faces of the late form of Lyme borreliosis.

INTRODUCTION: Acrodermatitis chronica atrophicans (ACA) is probably the most common late and chronic manifestation of the Lyme borreliosis seen in European patients. AIM: To analyze epidemiological data, and to investigate the effects of treatment of patients with ACA. MATERIAL AND METHODS: Nine patients were included in the study. All patients had serological examinations (ELISA and Western blot) and histopathological examination of the skin lesions performed. Eight patients had PCR in the skin biopsy performed. RESULTS: The duration of symptoms ranged from 2 months to 2 years. In 7 patients, skin lesions were located on lower limbs, in 2 patients - in a non-typical body area - abdomen. In 1 patient, scleroderma and in 3 patients, diabetes mellitus was diagnosed. Borrelia burgdorferi DNA was detected in 25% of the skin biopsy specimens. IgG anti-B. burgdorferi specific antibodies were present in serum of all patients (confirmed by Western blot). In all cases, the diagnosis was confirmed by histopathological examination. The response to ceftriaxone therapy varied. In 5 cases, the lesions resolved completely, in others they faded. CONCLUSIONS: Despite raising awareness of Lyme borreliosis, late forms of the disease such as ACA are still observed. Acrodermatitis chronica atrophicans skin lesions may be located in non-characteristic areas, e.g. abdominal skin. Symptoms are not irritating or painful, therefore patients do not seek medical help. The effect of antibiotic treatment varies.

The increased concentration of macrophage migration inhibitory factor in serum and cerebrospinal fluid of patients with tick-borne encephalitis.

BACKGROUND: Host factors determining the clinical presentation of tick-borne encephalitis (TBE) are not fully elucidated. The peripheral inflammatory response to TBE virus is hypothesized to facilitate its entry into central nervous system by disrupting the blood-brain barrier with the involvement of a signaling route including Toll-like receptor 3 (TLR3) and pro-inflammatory cytokines macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNFα), and interleukin-1 beta (IL-1ß). METHODS: Concentrations of MIF, TNFα, and IL-1ß were measured with commercial ELISA in serum and cerebrospinal fluid (CSF) from 36 hospitalized TBE patients, 7 patients with non-TBE meningitis, and 6 controls. The CSF albumin quotient (AQ) was used as a marker of blood-brain barrier permeability. Single nucleotide polymorphisms rs3775291, rs5743305 (associated with TLR3 expression), and rs755622 (associated with MIF expression) were assessed in blood samples from 108 TBE patients and 72 non-TBE controls. The data were analyzed with non-parametric tests, and p < 0.05 was considered significant. RESULTS: The median serum and CSF concentrations of MIF and IL-1ß were significantly increased in TBE group compared to controls. MIF concentration in serum tended to correlate with AQ in TBE, but not in non-TBE meningitis. The serum concentration of TNFα was increased in TBE patients bearing a high-expression TLR3 rs5743305 TT genotype, which also associated with the increased risk of TBE. The low-expression rs3775291 TLR3 genotype TT associated with a prolonged increase of CSF protein concentration. The high-expression MIF rs755622 genotype CC tended to correlate with an increased risk of TBE, and within TBE group, it was associated with a mild presentation. CONCLUSIONS: The results point to the signaling route involving TLR3, MIF, and TNFα being active in TBE virus infection and contributing to the risk of an overt neuroinvasive disease. The same factors may play a protective role intrathecally contributing to the milder course of neuroinfection. This suggests that the individual variability of the risk and clinical presentation of TBE might be traced to the variable peripheral and intrathecal expression of the mediators of the inflammatory response, which in turn associates with the host genetic background.

Evaluation of NF-κB concentration in patients with tick-borne encephalitis, neuroborreliosis, anaplasmosis and Anaplasma phagocythophilum with tick-borne encephalitis virus co-infection.

OBJECTIVES: The aim of the study was the evaluation of NF-κB concentration in serum and cerebrospinal fluid (CSF) of patients with diagnosis of tick-borne diseases: tick-borne encephalitis (TBE), neuroborreliosis (NB), anaplasmosis (ANA) and patients co-infected with tick-borne encephalitis virus and Anaplasma phagocythophilum (TBE+ANA). Additionally NF-κB concentration during acute and convalescent period was compared. METHODS: Sixty-seven patients with diagnosis of tick-borne diseases were included in the study. The control group (CG) consisted of 18 patients hospitalized because of headaches and had lumbar puncture performed. The NF-κB was measured by human inhibitory subunit of NF-κB ELISA Kit during acute and convalescent period. RESULTS: In serum the significant differences were observed only in patients with TBE+ANA co-infection. In CSF the concentration of NF-κB was significantly higher in patients with TBE, TBE+ANA co-infection, and patients with NB than in CG. Receiver operating characteristic (ROC) curves analysis showed that NF-κB concentration in CSF differentiated patients with NB with CG; patients co-infected with TBE and ANA with CG and patients with TBE with CG. NF-κB concentration in serum differentiated patients co-infected with TBE and ANA with NB and with ANA, with TBE and with CG. In TBE group the serum NF-κB concentration significantly decreased in convalescent period, while in NB and TBE groups significant CSF decrease of NF-κB concentration was observed.

Usefulness of copeptin as a potential biomarker in TBE.

OBJECTIVE: The aim of the study was to evaluate the usefulness of copeptin for differentiation of hyponatremia in the course of tick-borne encephalitis (TBE) and for being a prognostic marker of the severity of TBE. MATERIALS AND METHODS: One hundred and fourteen patients with TBE were included in the study. The control group consisted of 62 patients diagnosed with viral meningitis. RESULTS: Copeptin concentration did not differ in patients with hyponatremia and normonatremia. Urinary sodium excretion to plasma copeptin (copeptin/UNa Secretion) ratio was significantly lower in Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion patients than in patients with hyponatremia of other origin. Mean copeptin concentration in TBE patients was higher than in control group (VM) patients. There were no differences between patients with severe and mild course of TBE. CONCLUSIONS: Copeptin/UNa ratio may be used as a potential biomarker of SIADH in patients with TBE. Copeptin concentration is significantly higher in patients with TBE than in viral meningitis of other origin, especially in patients aged 18-34 and >49 years old. Copeptin does not differentiate TBE of mild and severe course.

Analysis of the relationship between single nucleotide polymorphism of the CD209, IL-10, IL-28 and CCR5 D32 genes with the human predisposition to developing tick-borne encephalitis.

<b>Introduction: </b>It is known that in the pathogenesis of tick-borne encephalitis (TBE) various molecules play a significant role. The most prominent factors include IL-10, IL-28B, CD-209 and CCR5. It is reasonable to search for genetic predispositions to the development of various clinical forms of TBE related to the genetic variation of IL-10, IL-28B, CD-209 and CCR5. In this study we aimed to search for the relationship between single nucleotide polymorphism in the promoter region of the CD209, IL-10, IL-28 and 32 base pair deletion in CCR5 coding region (Δ 32) with the human predisposition to development of various clinical presentations of TBE. We tried to assess the relation between the presence of particular alleles and genotypes with laboratory and clinical parameters. <b>Material/Methods </b>59 patients with TBE and 57 people, bitten by a tick who never developed TBE (Polish cohort), were included in the study. To assess the distribution of single nucleotide polymorphisms, TaqMan SNP genotyping assays were used for IL10: rs1800872 and rs1800896, for CD 209 rs4804803 and rs2287886, rs12979860 for IL 28B SNPs according to the manufacturer's protocol using real-time PCR technology on the StepOne thermal cycler. <b>Results </b>Comparison between TBE patients and CG showed that in SNP rs2287886 CD 209 AG heterozygotes were more frequent in the TBE group, while homozygotes GG were more frequent in the CG group. <b>Conclusions </b> SNP rs2287886 CD 209 AG heterozygotes predispose humans to develop TBE. Single nucleotide polymorphism in the promoter region of the CD209, IL-10, IL-28 and CCR5 D32 genes does not correlate with the severity of TBE.

The expression of the chemokine receptor CCR5 in tick-borne encephalitis.

BACKGROUND: Chemokine receptor 5 (CCR5) is hypothesized to drive the lymphocyte migration to central nervous system in flavivirus encephalitis, and the non-functional CCR5Δ32 genetic variant was identified as a risk factor of a West Nile virus infection and of tick-borne encephalitis (TBE). We have attempted to investigate how CCR5 expression corresponds to the clinical course and severity of TBE. METHODS: We have repeatedly studied CCR5 expression in 76 patients during encephalitic and convalescent TBE phase, analyzing its association with clinical features, cerebrospinal fluid (csf) pleocytosis, and concentrations of CCR5 ligands (chemokines CCL3, CCL4, and CCL5) and CCR5 genotype. Fifteen patients with neuroborreliosis, 7 with aseptic meningitis, 17 in whom meningitis/encephalitis had been excluded, and 18 healthy blood donors were studied as controls. Expression of CCR5 was measured cytometrically in blood and csf-activated Th lymphocytes (CD3+CD4+CD45RO+). Concentrations of chemokines in serum and csf were measured immunoenzymatically, and CCR5Δ32 was detected with sequence-specific primers. Data were analyzed with non-parametric tests, and p < 0.05 was considered significant. RESULTS: The blood expression of CCR5 did neither differ between the groups nor change in the course of TBE. The CCR5 expression in the inflammatory csf was several-fold increased in comparison with blood but lower in TBE than in neuroborreliosis. The csf concentration of CCL5 was increased in TBE, the highest in the most severe presentation (meningoencephalomyelitis) and correlated with pleocytosis. The CCR5Δ32/wt genotype present in 7 TBE patients was associated with a decreased CCR5 expression, but enrichment of csf Th population in CCR5-positive cells and the intrathecal inflammatory response were preserved, without a compensatory increase of CCL5 expression. CONCLUSIONS: We infer CCR5 and CCL5 participate in the response to TBE virus, as well as to other neurotropic pathogens. The intrathecal response to TBE is not hampered in the bearers of a single copy of CCR5Δ32 allele, suggesting that the association of CCR5Δ32 with TBE may be mediated in the periphery at the earlier stage of the infection. Otherwise, a variability of the CCR5 expression in the peripheral blood lymphocytes seems not to be associated with a variable susceptibility to TBE.

Influence of climatic, demographic and socioeconomic factors on tick-borne encephalitis incidence in 6 counties of Podlaskie region in 1994-2014.

OBJECTIVES: The aim of the study was the analysis of possible influence of meteorologic, socioeconomic factors and land cover changes on tick borne encephalitis (TBE) incidence in Podlaskie region. We analyzed data from 6 counties in Podlaskie region (bialostocki, suwalski, hajnowski, grajewski, kolnenski, siemiatycki) from years 1994-2014. MATERIALS AND METHODS: The analyzed data included: mean, minimal, maximal air temperatures (measured at 2 m above ground level), temperature amplitudes, rainfall, number of days with snowfall and duration of snow cover presence, population of each county, number of people employed as foresters, hunters, farmers and unemployed, area of each county, forests and agricultural area. RESULTS: The statistical analysis showed correlations between TBE incidence and mean air temperatures in April and July. Moreover we stated correlation between TBE incidence and precipitation in April. TBE incidence was significantly higher in counties with high percentage of forested area. No significant correlations between TBE incidence and socioeconomic factors and land cover changes were observed.

Increased concentration of interferon lambda-3, interferon beta and interleukin-10 in the cerebrospinal fluid of patients with tick-borne encephalitis.

Tick-borne encephalitis (TBE) has a wide clinical spectrum, from asymptomatic to severe encephalitis, and host-dependent factors determining the outcome remain elusive. We have measured concentrations of pro-inflammatory/Th1 interferon-γ (IFNγ), immunomodulatory/Th2 interleukin-10 (IL-10), anti-viral type I (IFNß) and type III (IFNλ3) interferons in cerebrospinal fluid (csf) and serum of 18 TBE patients, simultaneously genotyped for polymorphisms associated with the expression of genes IFNL3 (coding IFNλ3), IL10, CD209 and CCR5. IL-10, IFNß and IFNλ3 were up-regulated in csf, with IFNλ3 level higher in patients with the milder clinical presentation (meningitis) than in meningoencephalitis. There was an increased serum IFNß and a tendency for increased serum IL-10 in meningitis patients. Genotype in rs12979860 locus upstream of IFNL3 was associated with IFNλ3 expression and in rs287886 (CD209) - IL-10 expression. IL-10, IFNß and IFNλ3 are expressed and play a protective role in TBE and their expression in TBE patients is associated with genetic polymorphisms.

Tuberculous meningitis--a case report.

In this paper we present a case of a 58 years old male with a rare form of extrapulmonary tuberculosis--tuberculous meningitis (TBM). Tuberculous meningitis is usually caused by hematogenous spread of Mycobacterium from lungs. The TBM is a severe disease with high mortality. The symptoms usually increase gradually and in the course of the disease 3 clinical stages (prodromal phase, phase of neurological symptoms and phase of paresis) may be differentiated. Cerebrospinal fluid examination, chest x-ray and sputum culture are crucial for diagnosis of TBM. The proper diagnosis and early causative treatment significantly improve the outcome of the disease.

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.

ssICAM-1, IL-21 and IL-23 in patients with tick borne encephalitis and neuroborreliosis.

OBJECTIVE: There have been few reports on the role of Intercellular Adhesion Molecule 1 (ICAM-1), but not interleukin-21 (IL-21) and interleukin-23 (IL-23) in tick-borne encephalitis (TBE) and neuroborreliosis (NB). We postulate that these two interleukins may participate in the early phase of TBE and NB. The aim of the study was to measure serum and cerebrospinal fluid (CSF) concentration of ICAM-1, IL-21 and IL-23 in patients with TBE and NB before treatment and to assess their usefulness in the diagnosis and monitoring of inflammatory process in TBE and NB. METHODS: Forty-three patients hospitalized in The Department of Infectious Diseases and Neuroinfections of Medical University in Bialystok, Poland, were included in the study. Patients were divided into three groups: TBE, NB and CG. Pre-treatment blood and CSF samples were obtained from all patients. ELISA kits (DRG Instruments, Germany) were used to measure the concentration of IL-21, IL-23 and sICAM-1. RESULTS: Significant differences between TBE/CG and NB/CG concentration of sICAM-1 were found only in the CSF. CSF IL-21 levels in NB were lower than in TBE. In TBE, a strong negative correlation between CSF concentration of IL-21 and IL-23 and monocyte count in CSF was observed. Negative correlation between IL-21 in CSF and neutrophil count was also noted. Serum IL-23 correlated positively with leukocytes and platelet count in serum. In NB, a strong positive correlation between serum IL-21 and platelet count and negative correlation between IL-21 in serum and CSF with pleocytosis was observed. CONCLUSIONS: Increased sICAM-1 concentration in TBE and NB may be a proof of brain-blood barrier disturbances in the early phase of these diseases. IL-21 and IL-23 do not appear to play an important role in the pathogenesis of the early stages of TBE and NB.