Magnitude and Functional Profile of the Human CD4+ T Cell Response throughout Primary Immunization with Tick-Borne Encephalitis Virus Vaccine.

Tick-borne encephalitis (TBE) is a viral infection of the CNS caused by TBE virus. With no specific treatment available, the only protection is a formalin-inactivated whole virus vaccine. Primary immunization with European TBE vaccines, as recommended by the manufacturers, consists of three vaccine doses administered within a 1-y period. Protection from vaccination is believed to be mediated by Abs, yet T cells may also have a protective role. We set out to characterize the human CD4+ T cell response throughout primary TBE immunization. The responses were evaluated before vaccination and 1 mo after each vaccine dose. A heterogeneous magnitude of CD4+ T cell-mediated memory responses was observed in regard to lymphoblast expansion and cytokine production (IFN-γ, IL-2, and TNF), with the highest median magnitude detected after the second dose of vaccine. Stimulation with an overlapping peptide library based on structural TBE virus proteins E and C revealed that CD4+ T cells concomitantly producing IL-2 and TNF dominated the responses from vaccinees after each vaccine dose, whereas a control cohort of TBE patients responded mainly with all three cytokines. CD107a expression was not upregulated upon peptide stimulation in the vaccinees. However, CD154 (CD40L) expression on cytokine-positive memory CD4+ T cells significantly increased after the second vaccine dose. Taken together, TBE vaccination induced CD4+ T cell responses dominated by IL-2 and TNF production together with CD154 upregulation and a lower IFN-γ response compared with TBE patients. This response pattern was consistent after all three doses of TBE vaccine.

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.

Selected Biomarkers of Tick-Borne Encephalitis: A Review.

Tick-borne encephalitis (TBE) is an acute disease caused by the tick-borne encephalitis virus. Due to the viral nature of the condition, there is no effective causal treatment for full-blown disease. Current and nonspecific TBE treatments only relieve symptoms. Unfortunately, the first phase of TBE is characterized by flu-like symptoms, making diagnosis difficult during this period. The second phase is referred to as the neurological phase as it involves structures in the central nervous system-most commonly the meninges and, in more severe cases, the brain and the spinal cord. Therefore, it is important that early markers of TBE that will guide clinical decision-making and the choice of treatment are established. In this review, we performed an extensive search of literature reports relevant to biomarkers associated with TBE using the MEDLINE/PubMed database. We observed that apart from routinely determined specific immunoglobulins, free light chains may also be useful in the evaluation of intrathecal synthesis in the central nervous system (CNS) during TBEV infection. Moreover, selected metalloproteinases, chemokines, or cytokines appear to play an important role in the pathogenesis of TBE as a consequence of inflammatory reactions and recruitment of white blood cells into the CNS. Furthermore, we reported promising findings on tau protein or Toll-like receptors. It was also observed that some people may be predisposed to TBE. Therefore, to understand the role of selected tick-borne encephalitis biomarkers, we categorized these factors and discussed their potential application in the diagnosis, prognosis, monitoring, or management of TBE.

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.

Suspected Neuro-invasive Powassan Virus Infection in a Pediatric Patient.

Powassan virus lineage II (POWV), also known as deer tick virus, is an emerging tick-borne pathogen transmitted by Ixodes scapularis, the natural vector for the organisms that causes Lyme disease, babesiosis, and anaplasmosis. POWV is the only tick-borne flavivirus in North America known to cause disease in humans. We present a suspected pediatric case of POWV infection in northern Wisconsin.

Analysis of Multiple Risk Factors for Seronegative Rate of Anti-Tick-Borne Encephalitis Virus Immunization in Human Serum.

Background and objectives: Tick-borne encephalitis virus (TBEV) infections have been the cause of threatening outbreaks for many years. Apart from several physical and chemical methods to prevent tick bites, active vaccination of people highly exposed to infection is still the most important strategy of prevention. However, in some subjects, the lack of or low response to TBEV antigens is observed. The aim of the current study was to assess the prevalence of seronegative rate for anti-TBEV antibodies and the risk factors for waning immunity. Materials and Methods: 2315 at least primary vaccinated subjects from the high risk group for TBEV infections participated in this study. A commercial enzyme-linked immunosorbent assay (ELISA) test was used for the assessment of anti-TBEV IgG serum level. Results: Data showed that 86.2% of subjects who underwent vaccination were positive for anti-TBEV antibodies within 5 years. As much as 13.8% of subjects that underwent primary or primary and booster vaccination were barely protected after vaccination. Women and subjects under 60 years underwent more effective protection but sex and older age was not a risk factor for being a subject of waning immunity. A logistic regression showed that both a longer time since the vaccination and a lower number of booster doses constantly increased the chance of lost anti-TBEV antibodies. Conclusions: This study demonstrates that the vaccination schedule should be reevaluated. The extension of the interval of booster immunization is risky and all subjects should be surrounded by care consisting of more frequent monitoring of serum antibodies by personalized schedule to adjust the frequency of subsequent doses of booster vaccination.

The prevalence and clinical characteristics of tick-borne diseases at One Sentinel Hospital in Northeastern China.

Northeastern China is a region of high tick abundance, multiple tick-borne pathogens and likely human infections. The spectrum of diseases caused by tick-borne pathogens has not been objectively evaluated in this region for clinical management and for comparison with other regions globally where tick-transmitted diseases are common. Based on clinical symptoms, PCR, indirect immunofluorescent assay and (or) blood smear, we identified and described tick-borne diseases from patients with recent tick bite seen at Mudanjiang Forestry Central Hospital. From May 2010 to September 2011, 42% (75/180) of patients were diagnosed with a specific tick-borne disease, including Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis, human babesiosis and spotted fever group rickettsiosis. When we compared clinical and laboratory features to identify factors that might discriminate tick-transmitted infections from those lacking that evidence, we revealed that erythema migrans and neurological manifestations were statistically significantly differently presented between those with and without documented aetiologies (P < 0.001, P = 0.003). Twelve patients (6.7%, 12/180) were co-infected with two tick-borne pathogens. We demonstrated the poor ability of clinicians to identify the specific tick-borne disease. In addition, it is necessary to develop specific laboratory assays for optimal diagnosis of tick-borne diseases.

Assessment of TLR-2 concentration in tick-borne encephalitis and neuroborreliosis.

The aim of the study was to check whether measurement of TLR-2 in serum or cerebrospinal fluid (CSF) can help differentiate between neuroborreliosis (NB) and tick-borne encephalitis (TBE). Eighty patients with meningitis and meningoencephalitis were divided into two groups: Group I - patients with NB (n = 40) and Group II - patients with TBE (n = 40). Diagnosis was based on the clinical picture, CSF examination and presence of specific antibodies in serum and CSF. The control group (CG) consisted of healthy blood donors (n = 25) and patients in whom inflammatory process in central nervous system was excluded (n = 25). Concentration of TLR-2 was measured using a commercial kit [TLR-2 Elisa Kit (EIAab, China)]. The serum and CSF TLR-2 concentration of NB patients was significantly higher than in CG. The serum and CSF TLR-2 concentration in TBE patients was significantly higher than in the CG. Receiver operating characteristic analysis of the serum TLR-2 concentration showed significant differences between the group of patients with NB and a group of patients with TBE. TLR-2 is involved in the development of inflammatory process in the CNS caused by both tick-borne pathogens: viral and bacterial as TLR-2 concentration in both CSF and serum differentiates these groups from healthy patients. Although TLR-2 cannot be used as a sole and reliable biomarker differentiating NB from TBE, results of our study are a step forward toward discovering such biomarker in the future.

Assessment of NS1 protein as an early diagnostic marker for Kyasanur forest disease virus.

BACKGROUND & OBJECTIVES: Due to the emergence of Kyasanur forest disease (KFD) virus to new regions in India, there is an urgent need to develop an early diagnostic system, which is cost-effective and can be efficiently used with minimum paraphernalia. The non-structural-1 (NS1) protein is known to be an early diagnostic marker for flaviviruses. Furthermore, NS1 antigen capture ELISA kits developed using bacterially expressed dengue NS1 protein are commercially available. METHODS: Based on the data available on dengue virus, West Nile virus and other flaviviruses, bacterially expressed Kyasanur forest disease virus (KFDV) NS1 protein and polyclonal serum raised against the NS1 protein in mice and rabbit were used to develop an antigen capture ELISA for early diagnosis of the virus. The feasibility of this ELISA was further tested using in silico predictions. RESULTS: KFDV NS1 gene was cloned, expressed and confirmed by SDS-PAGE and western blotting. An antigen detection ELISA was standardized and sensitivity and specificity was tested with other flaviviruses. KFDV acute phase 43 samples were tested and only two were found to be positive for KFDV NS1 antigen. Superimposition of KFDV NS1 and TBEV NS1 revealed a root mean square distance (RMSD) of ~0.79 Å covering 1220 backbone atoms. This implies that the structures are very similar in terms of 3D fold. The identity of amino acid composition between these proteins was 73.4% and similarity was 92.9%, as revealed from the pairwise comparison. INTERPRETATION & CONCLUSION: The study points out that the half-life, expression and secretion levels of KFDV NS1 protein are not sufficient enough for its use as early diagnostic marker. The protein may have to be expressed in eukaryotic host to counter the lack of glycosylation in bacterial plasmid based expression of proteins. Hence, bacterially expressed KFDV NS1 protein may not be an ideal early diagnostic marker for the virus.

Outbreak of alimentary tick-borne encephalitis in Podlaskie voivodeship, Poland

INTRODUCTION: Tick-borne encephalitis (TBE) virus remains one of the main etiological agents of central nervous system infections in Europe. The disease occurs endemically in Central and Eastern Europe, Southern part of Russia and Scandinavia. Between 2000 and 2015 there were 3 662 registered TBE cases in Poland and approximately 45% of them were reported in Podlaskie voivodeship. TBE typically develops as a result of being bitten by infected tick, however, it can also be a consequence of ingestion of unpasteurized milk from viremic animal. OBJECTIVES: The aim of the article was to underline to the importance of TBE virus transmission via alimentary route and clinical description of four patients who developed TBE as a result of raw goat milk consumption. MATERIAL AND METHODS: A retrospective analysis of documentation of four patients hospitalized in Observational-Infectious Department of Independent Public Healthcare Centre in Hajnówka and Department of Infectious Diseases and Neuroinfections at the Medical University of Bialystok from June 10th 2017 to July 11th 2017 due to alimentary TBE. RESULTS: Patients were between 24 and 36 years of age. They have consumed goat milk from the same source. None of the patients have been vaccinated against TBE virus. In all patients typical biphasic disease course with the presence of prodromal and neurological phase was observed. TBE was confirmed by demonstration of anti-TBE antibodies in serum and/or cerebrospinal fluid of patients. CONCLUSIONS: Diagnosis of TBE should be considered in every case of encephalitis in endemic areas. Due to the risk of TBE infection after consumption of unpasteurized milk from livestock, it is crucial to raise awareness of general population and farm owners about the possibility of TBE infection via alimentary route.

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.

Distinction between serological responses following tick-borne encephalitis virus (TBEV) infection vs vaccination, Sweden 2017.

Tick-borne encephalitis virus (TBEV) is an important European vaccine-preventable pathogen. Discrimination of vaccine-induced antibodies from those elicited by infection is important. We studied anti-TBEV IgM/IgG responses, including avidity and neutralisation, by multiplex serology in 50 TBEV patients and 50 TBEV vaccinees. Infection induced antibodies reactive to both whole virus (WV) and non-structural protein 1 (NS1) in 48 clinical cases, whereas 47 TBEV vaccinees had WV, but not NS1 antibodies, enabling efficient discrimination of infection/vaccination.

Effectiveness of primary vaccination against tick-borne encephalitis in employees of the armed forces.

OBJECTIVE: The aim of our study is to evaluate immune response after receiving the primary vaccination against tick-borne encephalitis (TBE), and to establish a link between seropositivity and selected factors in soldiers. METHODS: Blood samples, questionnaires and vaccination records were obtained. TBE antibodies were detected using both ELISA and a neutralization test (NT). We used logistic regression for statistical analysis. RESULTS: Overall, seropositivity (presence of IgG) was detected in 88% of participants. The proportion of seropositive subjects in relation to the number of doses of vaccine was 69% (2 doses) and 91% (3 doses). A statistically significant relationship was found between seropositivity and the number of vaccine doses. No statistical significance was identified in relation to age and sex. There was no statistical significance of seropositivity, depending on the time of the last dose of the vaccine. CONCLUSIONS: TBE immunisation should be targeted at individuals in the most affected locations and those at highest risk of exposure according to lifestyle and occupation.

Tick-Borne Encephalitis Virus in Ticks and Roe Deer, the Netherlands.

We report the presence of tick-borne encephalitis virus (TBEV) in the Netherlands. Serologic screening of roe deer found TBEV-neutralizing antibodies with a seroprevalence of 2%, and TBEV RNA was detected in 2 ticks from the same location. Enhanced surveillance and awareness among medical professionals has led to the identification of autochthonous cases.

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.

Goats as sentinel hosts for the detection of tick-borne encephalitis risk areas in the Canton of Valais, Switzerland.

BACKGROUND: Tick-borne encephalitis (TBE) is an important tick-borne disease in Europe. Detection of the TBE virus (TBEV) in local populations of Ixodes ricinus ticks is the most reliable proof that a given area is at risk for TBE, but this approach is time-consuming and expensive. A cheaper and simpler approach is to use immunology-based methods to screen vertebrate hosts for TBEV-specific antibodies and subsequently test the tick populations at locations with seropositive animals. RESULTS: The purpose of the present study was to use goats as sentinel animals to identify new risk areas for TBE in the canton of Valais in Switzerland. A total of 4114 individual goat sera were screened for TBEV-specific antibodies using immunological methods. According to our ELISA assay, 175 goat sera reacted strongly with TBEV antigen, resulting in a seroprevalence rate of 4.3%. The serum neutralization test confirmed that 70 of the 173 ELISA-positive sera had neutralizing antibodies against TBEV. Most of the 26 seropositive goat flocks were detected in the known risk areas in the canton of Valais, with some spread into the connecting valley of Saas and to the east of the town of Brig. One seropositive site was 60 km to the west of the known TBEV-endemic area. At two of the three locations where goats were seropositive, the local tick populations also tested positive for TBEV. CONCLUSION: The combined approach of screening vertebrate hosts for TBEV-specific antibodies followed by testing the local tick population for TBEV allowed us to detect two new TBEV foci in the canton of Valais. The present study showed that goats are useful sentinel animals for the detection of new TBEV risk areas.

Comparison of hyponatremia and SIADH frequency in patients with tick borne encephalitis and meningitis of other origin.

AIM: The aim of the study was the evaluation of frequency and origin of hyponatremia in tick borne encephalitis (TBE) in comparison to non-TBE viral meningitis and bacterial meningitis. METHODS: A total of 124 patients aged 18-80 years, with TBE were included to the study. The mild form of TBE was diagnosed in 59 patients, while the severe form was diagnosed in 65 patients. The first control group (VMG) consisted of 72 patients with viral meningitis, but excluded TBE. The second control group (BMG) consisted of 16 patients diagnosed with bacterial meningitis. RESULTS: Hyponatremia was diagnosed in 55 (44.4%) patients with TBE. In 12 (9.7%) patients (mean age 56.6 ± 19.9 years; 9 men, 3 women) syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was diagnosed. In VMG hyponatremia was diagnosed in 7 (9.7%) patients. In the age group <35 years and in the age group of 50-64 years the frequency of hyponatremia and SIADH was higher in TBE than in VMG (p < 0.05). In BMG hyponatremia was diagnosed in 6 (37.5%) patients. No statistically significant differences in frequency of hyponatremia between BMG and TBE groups were observed. CONCLUSIONS: (1) Hyponatremia is a common disorder in TBE and is more frequent than in other viral types of meningitis, especially in young patients (< 35 years). (2) The most common cause of hyponatremia in TBE patients is dehydration and fluid supplementation should be a treatment of choice. (3) Overall, 16.9% of the patients with the severe form of TBE develop SIADH syndrome and they required treatment based on fluid restriction and hypertonic saline infusion.

IgG Avidity: an Important Serologic Marker for the Diagnosis of Tick-Borne Encephalitis Virus Infection.

A total of 52 serum samples from patients with symptoms suggestive of tick-borne encephalitis virus (TBEV) infection and positive IgM and/or IgG antibodies were tested for IgG avidity. Acute/recent TBEV infection was confirmed by low/borderline avidity index (AI) in 94.8% IgM positive/IgG positive samples, while in 5.2% high AI was found indicating persisting IgM antibodies. Majority of IgM negative/IgG positive samples (78.6%) showed high AI consistent with past TBEV infection. However, in 21.3% patients without measurable IgM antibodies current/recent infection was confirmed by AI. IgG avidity represents an additional serologic marker that improves diagnosis of TBEV, especially in cases of atypical antibody response.