scholarly journals Two Cases of Severe Tick-Borne Encephalitis in Rituximab-Treated Patients in Germany: Implications for Diagnosis and Prevention

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Philipp A Steininger ◽  
Tobias Bobinger ◽  
Wenke Dietrich ◽  
De-Hyung Lee ◽  
Michael Knott ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
B Cell ◽  
Standard Therapy ◽  
Laboratory Diagnosis ◽  
Antibody Responses ◽  
B Cell Malignancies ◽  
Tick Borne Encephalitis ◽  
Preventive Vaccination ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

Abstract Rituximab (RTX) has become a standard therapy for certain B cell malignancies and autoimmune diseases. We report 2 RTX-treated patients who developed severe tick-borne encephalitis virus (TBEV) infection. The inability to generate new antibody responses renders RTX-treated patients susceptible to TBEV, impedes laboratory diagnosis, and necessitates preventive vaccination in endemic areas.

TBE in Austria

2021 ◽  
Author(s):  
Karin Stiasny ◽  
Heidemarie Holzmann ◽  
Isabel Santonja ◽  
Franz X. Heinz
Keyword(s):  
Laboratory Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Reference Laboratory ◽  
Chain Reaction ◽  
National Reference ◽  
Tick Borne Encephalitis ◽  
Polymerase Chain ◽  
Tick Borne Encephalitis Virus ◽  
Medical University ◽  
Tbev Infection

Since 1972, the documentation of human cases of tick-borne encephalitis (TBE) in Austria has been performed by the Center for Virology, Medical University of Vienna, which acts as the National Reference Laboratory for TBE and other flavivirus infections. Only hospitalized patients with a recent tick-borne encephalitis virus (TBEV) infection confirmed by laboratory diagnosis are counted as cases. Confirmation is usually based on immunoglobulin (Ig) serology (namely enzyme-linked immunosorbent assay [ELISA] for IgM and IgG). However, this confirmation may be supplemented by virus neutralization and polymerase chain reaction (PCR) analyses if needed.

TBE in Austria

2020 ◽  
Keyword(s):  
Laboratory Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Reference Laboratory ◽  
Chain Reaction ◽  
National Reference ◽  
Tick Borne Encephalitis ◽  
Polymerase Chain ◽  
Tick Borne Encephalitis Virus ◽  
Medical University ◽  
Tbev Infection

Since 1972, the documentation of human cases of tick-borne encephalitis (TBE) in Austria has been performed by the Center for Virology, Medical University of Vienna, which acts as the National Reference Laboratory for TBE and other flavivirus infections. Only hospitalized patients with a recent tick-borne encephalitis virus (TBEV) infection confirmed by laboratory diagnosis are counted as cases. Confirmation is usually based on immunoglobulin (Ig) serology (namely enzyme-linked immunosorbent assay [ELISA] for IgM and IgG). However, this confirmation may be supplemented by virus neutralization and polymerase chain reaction (PCR) analyses if needed.

scholarly journals Infection and injury of human astrocytes by tick-borne encephalitis virus

2014 ◽  
Vol 95 (11) ◽  
pp. 2411-2426 ◽  
Author(s):  
Martin Palus ◽  
Tomáš Bílý ◽  
Jana Elsterová ◽  
Helena Langhansová ◽  
Jiří Salát ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Encephalitis Virus ◽  
Ultrastructural Changes ◽  
Interferon Α ◽  
Human Astrocytes ◽  
Tick Borne Encephalitis ◽  
Infected Cells ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection ◽  
Pro Inflammatory Cytokines

Tick-borne encephalitis (TBE), a disease caused by tick-borne encephalitis virus (TBEV), represents the most important flaviviral neural infection in Europe and north-eastern Asia. In the central nervous system (CNS), neurons are the primary target for TBEV infection; however, infection of non-neuronal CNS cells, such as astrocytes, is not well understood. In this study, we investigated the interaction between TBEV and primary human astrocytes. We report for the first time, to the best of our knowledge, that primary human astrocytes are sensitive to TBEV infection, although the infection did not affect their viability. The infection induced a marked increase in the expression of glial fibrillary acidic protein, a marker of astrocyte activation. In addition, expression of matrix metalloproteinase 9 and several key pro-inflammatory cytokines/chemokines (e.g. tumour necrosis factor α, interferon α, interleukin (IL)-1β, IL-6, IL-8, interferon γ-induced protein 10, macrophage inflammatory protein, but not monocyte chemotactic protein 1) was upregulated. Moreover, we present a detailed description of morphological changes in TBEV-infected cells, as investigated using three-dimensional electron tomography. Several novel ultrastructural changes were observed, including the formation of unique tubule-like structures of 17.9 ±0.15 nm diameter with associated viral particles and/or virus-induced vesicles and located in the rough endoplasmic reticulum of the TBEV-infected cells. This is the first demonstration that TBEV infection activates primary human astrocytes. The infected astrocytes might be a potential source of pro-inflammatory cytokines in the TBEV-infected brain, and might contribute to the TBEV-induced neurotoxicity and blood–brain barrier breakdown that occurs during TBE. The neuropathological significance of our observations is also discussed.

scholarly journals Tick populations from endemic and non-endemic areas in Germany show differential susceptibility to TBEV

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Katrin Liebig ◽  
Mathias Boelke ◽  
Domenic Grund ◽  
Sabine Schicht ◽  
Andrea Springer ◽  
...  
Keyword(s):  
Differential Susceptibility ◽  
Feeding Rates ◽  
Infection Rates ◽  
Lower Saxony ◽  
Tick Borne Encephalitis ◽  
The Central Nervous System ◽  
Tick Borne Encephalitis Virus ◽  
In Vitro Feeding ◽  
Tbev Infection

Abstract Tick-borne encephalitis virus (TBEV) is endemic in twenty-seven European countries, transmitted via the bite of an infected tick. TBEV is the causative agent of one of the most important viral diseases of the central nervous system (CNS). In Germany, 890 human cases were registered between the years 2018–2019. The castor bean tick, Ixodes ricinus, is the TBEV vector with the highest importance in Central Europe, including Germany. Despite the nationwide distribution of this tick species, risk areas of TBEV are largely located in Southern Germany. To increase our understanding of TBEV-tick interactions, we collected ticks from different areas within Germany (Haselmühl/Bavaria, Hanover/Lower Saxony) and infected them via an in vitro feeding system. A TBEV isolate was obtained from an endemic focus in Haselmühl. In two experimental series conducted in 2018 and 2019, ticks sampled in Haselmühl (TBEV focus) showed higher artificial feeding rates, as well as higher TBEV infections rates than ticks from the non-endemic area (Hanover). Other than the tick origin, year and month of the infection experiment as well as co-infection with Borrelia spp., had a significant impact on TBEV Haselmühl infection rates. Taken together, these findings suggest that a specific adaptation of the tick populations to their respective TBEV virus isolates or vice versa, leads to higher TBEV infection rates in those ticks. Furthermore, co-infection with other tick-borne pathogens such as Borrelia spp. can lower TBEV infection rates in specific populations.

scholarly journals A Functional Toll-Like Receptor 3 Gene (TLR3) May Be a Risk Factor for Tick-borne Encephalitis Virus (TBEV) Infection

2011 ◽  
Vol 203 (4) ◽  
pp. 523-528 ◽  
Author(s):  
Elin Kindberg ◽  
Sirkka Vene ◽  
Aukse Mickiene ◽  
Åke Lundkvist ◽  
Lars Lindquist ◽  
...  
Keyword(s):  
Risk Factor ◽  
Encephalitis Virus ◽  
Toll Like Receptor ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

scholarly journals Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

2015 ◽  
Vol 59 (9) ◽  
pp. 5483-5493 ◽  
Author(s):  
Luděk Eyer ◽  
James J. Valdés ◽  
Victor A. Gil ◽  
Radim Nencka ◽  
Hubert Hřebabecký ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Antiviral Effect ◽  
Encephalitis Virus ◽  
Nucleoside Analogues ◽  
Kidney Cells ◽  
Porcine Kidney ◽  
Human Neuroblastoma ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

ABSTRACTTick-borne encephalitis virus (TBEV) is a leading cause of human neuroinfections in Europe and Northeast Asia. There are no antiviral therapies for treating TBEV infection. A series of nucleoside analogues was tested for the ability to inhibit the replication of TBEV in porcine kidney cells and human neuroblastoma cells. The interactions of three nucleoside analogues with viral polymerase were simulated using advanced computational methods. The nucleoside analogues 7-deaza-2′-C-methyladenosine (7-deaza-2′-CMA), 2′-C-methyladenosine (2′-CMA), and 2′-C-methylcytidine (2′-CMC) inhibited TBEV replication. These compounds showed dose-dependent inhibition of TBEV-induced cytopathic effects, TBEV replication (50% effective concentrations [EC50]of 5.1 ± 0.4 μM for 7-deaza-2′-CMA, 7.1 ± 1.2 μM for 2′-CMA, and 14.2 ± 1.9 μM for 2′-CMC) and viral antigen production. Notably, 2′-CMC was relatively cytotoxic to porcine kidney cells (50% cytotoxic concentration [CC50] of ∼50 μM). The anti-TBEV effect of 2′-CMA in cell culture diminished gradually after day 3 posttreatment. 7-Deaza-2′-CMA showed no detectable cellular toxicity (CC50> 50 μM), and the antiviral effect in culture was stable for >6 days posttreatment. Computational molecular analyses revealed that compared to the other two compounds, 7-deaza-2′-CMA formed a large cluster near the active site of the TBEV polymerase. High antiviral activity and low cytotoxicity suggest that 7-deaza-2′-CMA is a promising candidate for further investigation as a potential therapeutic agent in treating TBEV infection.

scholarly journals Experience of application of IgY-technology for laboratory diagnostics of viral infections

2020 ◽  
Vol 65 (1) ◽  
pp. 21-26 ◽  
Author(s):  
A. P. Ivanov ◽  
T. D. Klebleeva ◽  
O. E. Ivanova
Keyword(s):  
Yellow Fever ◽  
Viral Infections ◽  
Yellow Fever Virus ◽  
Laboratory Diagnosis ◽  
Encephalitis Virus ◽  
Fever Virus ◽  
Laboratory Animals ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Introduction. The well-known advantages of class Y antibodies (IgY) from egg yolks of immunized hens in comparison with class G antibodies (IgG) of laboratory animals traditionally used in laboratory diagnosis of infectious diseases determine the stable interest of researchers in using IgY for these purposes (IgY technology) . Over the past 20 years, the obvious benefits of IgY technology have been demonstrated for a number of viral and bacterial infections. Goals and objectives. Construction of ELISA systems based on specific IgY for laboratory diagnosis of infections caused by tick-borne encephalitis virus, yellow fever virus, poliovirus.Material and methods. Obtaining yolk preparations of immunized chickens, obtaining highly purified IgY preparations (salting out, affinity chromatography), constructing ELISA systems for determining virus-specific antigens, testing the parameters of ELISA systems.Results and discussion. For the first time in laboratory practice, ELISA systems based on the use of specific polyclonal IgY were designed for laboratory diagnosis of topical human viral infections caused by flaviviruses and enteroviruses: determination of antigens of tick-borne encephalitis virus, yellow fever virus, 3 types of poliovirus. It was experimentally shown that these ELISA systems have high sensitivity and specificity, which allows them to be used for the semiquantitative and quantitative determination of antigens of these viruses in various materials (infected cell cultures, vaccines, etc.).Conclusion. The ELISA systems developed on the basis of specific IgY for determination of viral antigens can be effectively used for laboratory diagnosis of a number of viral infections, for the validation and control of vaccine preparations.

TBE in France

2019 ◽  
Author(s):  
Yves Hansmann ◽  
Aurélie Velay
Keyword(s):  
Human Case ◽  
Encephalitis Virus ◽  
Eastern Region ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

The first human case of tick-borne encephalitis virus (TBEV) infection in France was reported in 1968 in Alsace, an eastern region next to the German border: a gamekeeper working in a forest near Strasbourg.

scholarly journals Identification of linear human B-cell epitopes of tick-borne encephalitis virus

2014 ◽  
Vol 11 (1) ◽  
Author(s):  
Suvi Kuivanen ◽  
Jussi Hepojoki ◽  
Sirkka Vene ◽  
Antti Vaheri ◽  
Olli Vapalahti
Keyword(s):  
B Cell ◽  
Encephalitis Virus ◽  
B Cell Epitopes ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Human B Cell

scholarly journals Changes in cytokine and chemokine profiles in mouse serum and brain, and in human neural cells, upon tick-borne encephalitis virus infection

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Petra Pokorna Formanova ◽  
Martin Palus ◽  
Jiri Salat ◽  
Vaclav Hönig ◽  
Michal Stefanik ◽  
...  
Keyword(s):  
Immune Response ◽  
Brain Tissue ◽  
Inflammatory Cytokines ◽  
Mouse Serum ◽  
Neural Cells ◽  
Tick Borne Encephalitis ◽  
Human Neural Cells ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection ◽  
Pro Inflammatory Cytokines

Abstract Background Tick-borne encephalitis (TBE) is a severe neuropathological disorder caused by tick-borne encephalitis virus (TBEV). Brain TBEV infection is characterized by extensive pathological neuroinflammation. The mechanism by which TBEV causes CNS destruction remains unclear, but growing evidence suggests that it involves both direct neuronal damage by the virus infection and indirect damage caused by the immune response. Here, we aimed to examine the TBEV-infection-induced innate immune response in mice and in human neural cells. We also compared cytokine/chemokine communication between naïve and infected neuronal cells and astrocytes. Methods We used a multiplexed Luminex system to measure multiple cytokines/chemokines and growth factors in mouse serum samples and brain tissue, and in human neuroblastoma cells (SK-N-SH) and primary cortical astrocytes (HBCA), which were infected with the highly pathogenic TBEV strain Hypr. We also investigated changes in cytokine/chemokine production in naïve HBCA cells treated with virus-free supernatants from TBEV-infected SK-N-SH cells and in naïve SK-N-SH cells treated with virus-free supernatants from TBEV-infected HBCA cells. Additionally, a plaque assay was performed to assess how cytokine/chemokine treatment influenced viral growth following TBEV infection. Results TBEV-infected mice exhibited time-dependent increases in serum and brain tissue concentrations of multiple cytokines/chemokines (mainly CXCL10/IP-10, and also CXCL1, G-CSF, IL-6, and others). TBEV-infected SK-N-SH cells exhibited increased production of IL-8 and RANTES and downregulated MCP-1 and HGF. TBEV infection of HBCA cells activated production of a broad spectrum of pro-inflammatory cytokines, chemokines, and growth factors (mainly IL-6, IL-8, CXCL10, RANTES, and G-CSF) and downregulated the expression of VEGF. Treatment of SK-N-SH with supernatants from infected HBCA induced expression of a variety of chemokines and pro-inflammatory cytokines, reduced SK-N-SH mortality after TBEV infection, and decreased virus growth in these cells. Treatment of HBCA with supernatants from infected SK-N-SH had little effect on cytokine/chemokine/growth factor expression but reduced TBEV growth in these cells after infection. Conclusions Our results indicated that both neurons and astrocytes are potential sources of pro-inflammatory cytokines in TBEV-infected brain tissue. Infected/activated astrocytes produce cytokines/chemokines that stimulate the innate neuronal immune response, limiting virus replication, and increasing survival of infected neurons.

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