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3 pages, 193 KiB

Open AccessEditorial

Editorial for the Special Issue: “Tick-Borne Encephalitis”

by Daniel Ruzek

Microorganisms 2023, 11(4), 934; https://doi.org/10.3390/microorganisms11040934 - 3 Apr 2023

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Abstract

Tick-borne encephalitis (TBE) is a disease caused by the tick-borne encephalitis virus (TBEV) [...] Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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15 pages, 509 KiB

Open AccessArticle

Clinical Characteristics of Patients with Tick-Borne Encephalitis (TBE): A European Multicentre Study from 2010 to 2017

by Benno Kohlmaier, Nina A. Schweintzger, Manfred G. Sagmeister, Vendula Švendová, Daniela S. Kohlfürst, Astrid Sonnleitner, Manuel Leitner, Andrea Berghold, Erich Schmiedberger, Franz Fazekas, Alexander Pichler, Jana Rejc-Marko, Daniel Růžek, Lucie Dufková, Darina Čejková, Petr Husa, Martina Pýchová, Lenka Krbková, Václav Chmelík, Věra Štruncová, Dace Zavadska, Guntis Karelis, Aukse Mickiene, Joanna Zajkowska, Petra Bogovič, Franc Strle, Werner Zenz and the EU-TICK-BO STUDY GROUP Show full author list Hide full author list

Microorganisms 2021, 9(7), 1420; https://doi.org/10.3390/microorganisms9071420 - 30 Jun 2021

Cited by 40 | Viewed by 4208

Abstract

Tick-borne encephalitis (TBE) virus is a major cause of central nervous system infections in endemic countries. Here, we present clinical and laboratory characteristics of a large international cohort of patients with confirmed TBE using a uniform clinical protocol. Patients were recruited in eight [...] Read more.

Tick-borne encephalitis (TBE) virus is a major cause of central nervous system infections in endemic countries. Here, we present clinical and laboratory characteristics of a large international cohort of patients with confirmed TBE using a uniform clinical protocol. Patients were recruited in eight centers from six European countries between 2010 and 2017. A detailed description of clinical signs and symptoms was recorded. The obtained information enabled a reliable classification in 553 of 555 patients: 207 (37.3%) had meningitis, 273 (49.2%) meningoencephalitis, 15 (2.7%) meningomyelitis, and 58 (10.5%) meningoencephalomyelitis; 41 (7.4%) patients had a peripheral paresis of extremities, 13 (2.3%) a central paresis of extremities, and 25 (4.5%) had single or multiple cranial nerve palsies. Five (0.9%) patients died during acute illness. Outcome at discharge was recorded in 298 patients. Of 176 (59.1%) patients with incomplete recovery, 80 (27%) displayed persisting symptoms or signs without recovery expectation. This study provides further evidence that TBE is a severe disease with a large proportion of patients with incomplete recovery. We suggest monitoring TBE in endemic European countries using a uniform protocol to record the full clinical spectrum of the disease. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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9 pages, 526 KiB

Open AccessArticle

Tick-Borne Encephalitis Vaccination Protects from Alimentary TBE Infection: Results from an Alimentary Outbreak

by Lidia Chitimia-Dobler, Alexander Lindau, Rainer Oehme, Malena Bestehorn-Willmann, Markus Antwerpen, Marco Drehmann, Thomas Hierl, Ute Mackenstedt and Gerhard Dobler

Microorganisms 2021, 9(5), 889; https://doi.org/10.3390/microorganisms9050889 - 21 Apr 2021

Cited by 13 | Viewed by 2602

Abstract

In May 2017, a hospitalized index case of tick-borne encephalitis (TBE) was confirmed by Serology. The case was linked to alimentary infection by raw milk from a goat farm in the region of Tübingen, Baden-Württemberg, Germany, where no previous TBE cases in the [...] Read more.

In May 2017, a hospitalized index case of tick-borne encephalitis (TBE) was confirmed by Serology. The case was linked to alimentary infection by raw milk from a goat farm in the region of Tübingen, Baden-Württemberg, Germany, where no previous TBE cases in the area had been reported before. The TBE focus was confirmed by isolation of the TBE virus from ticks and Serological confirmation of past infection in one of the five flock goats. Additional investigations by the local public health office identified 27 consumers of goat milk at the putative period of exposure. For 20/27 exposed persons, anamnestic information was gained by the local public health office. Twelve/fourteen exposed and non-vaccinated people developed clinical illness and were confirmed as TBE cases by Serology. Five/six vaccinated and exposed people did not develop the disease. The one exposed and vaccinated person had their last TBE vaccination booster more than 15 years ago, and therefore a booster was more than 10 years overdue. None of the regularly vaccinated and exposed persons developed clinical overt TBE infection. We report the first known TBE outbreak, during which, protection by TBE vaccination against alimentary TBE infection was demonstrated. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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14 pages, 1379 KiB

Open AccessArticle

Enteric Ganglioneuritis, a Common Feature in a Subcutaneous TBEV Murine Infection Model

by Mathias Boelke, Christina Puff, Kathrin Becker, Fanny Hellhammer, Frederic Gusmag, Hannah Marks, Katrin Liebig, Karin Stiasny, Gerhard Dobler, Wolfgang Baumgärtner, Claudia Schulz and Stefanie C. Becker

Microorganisms 2021, 9(4), 875; https://doi.org/10.3390/microorganisms9040875 - 18 Apr 2021

Cited by 8 | Viewed by 3193

Abstract

Tick-borne encephalitis (TBE) is a severe neurologic disease in Europe and Asia. Disease expression ranges from asymptomatic to severe neurological clinical pictures, involving meningitis, encephalitis, meningoencephalitis and potentially fatal outcome. Humans mostly become infected with TBE virus (TBEV) by the bite of an [...] Read more.

Tick-borne encephalitis (TBE) is a severe neurologic disease in Europe and Asia. Disease expression ranges from asymptomatic to severe neurological clinical pictures, involving meningitis, encephalitis, meningoencephalitis and potentially fatal outcome. Humans mostly become infected with TBE virus (TBEV) by the bite of an infected tick. Gastrointestinal (GI) symptoms in humans are mainly attributed to the first viremic phase of TBEV infection with unspecific symptoms and/or resulting from severe neurological impairment of the central nervous system (CNS). We used the subcutaneous TBEV-infection of C57BL/6 mice as a model to analyze GI complications of TBE. We observed the acute distension and segmental dilation of the intestinal tract in 10 of 22 subcutaneously infected mice. Histological analysis revealed an intramural enteric ganglioneuritis in the myenteric and submucosal plexus of the small and large intestine. The numbers of infiltrating macrophages and CD3⁺ T lymphocytes correlated with the severity of ganglioneuritis, indicating an immune-mediated pathogenesis due to TBEV-infection of the enteric plexus. Our study demonstrates that the inflammation of enteric intramural ganglia presents to be a common feature in TBEV-infected mice. Accordingly, the results of this mouse model emphasize that GI disease manifestation and consequences for long-term sequelae should not be neglected for TBEV-infections in humans and require further investigation. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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12 pages, 439 KiB

Open AccessArticle

Comparison of Clinical, Laboratory and Immune Characteristics of the Monophasic and Biphasic Course of Tick-Borne Encephalitis

by Petra Bogovič, Stanka Lotrič-Furlan, Tatjana Avšič-Županc, Miša Korva, Andrej Kastrin, Lara Lusa, Klemen Strle and Franc Strle

Microorganisms 2021, 9(4), 796; https://doi.org/10.3390/microorganisms9040796 - 10 Apr 2021

Cited by 12 | Viewed by 2297

Abstract

The biphasic course of tick-borne encephalitis (TBE) is well described, but information on the monophasic course is limited. We assessed and compared the clinical presentation, laboratory findings, and immune responses in 705 adult TBE patients: 283 with monophasic and 422 with biphasic course. [...] Read more.

The biphasic course of tick-borne encephalitis (TBE) is well described, but information on the monophasic course is limited. We assessed and compared the clinical presentation, laboratory findings, and immune responses in 705 adult TBE patients: 283 with monophasic and 422 with biphasic course. Patients with the monophasic course were significantly (p ≤ 0.002) older (57 vs. 50 years), more often vaccinated against TBE (7.4% vs. 0.9%), more often had comorbidities (52% vs. 37%), and were more often treated in the intensive care unit (12.4% vs. 5.2%). Multivariate logistic regression found strong association between the monophasic TBE course and previous TBE vaccination (OR = 18.45), presence of underlying illness (OR = 1.85), duration of neurologic involvement before cerebrospinal fluid (CSF) examination (OR = 1.39), and patients’ age (OR = 1.02). Furthermore, patients with monophasic TBE had higher CSF levels of immune mediators associated with innate and adaptive (Th1 and B-cell) immune responses, and they had more pronounced disruption of the blood–brain barrier. However, the long-term outcome 2–7 years after TBE was comparable. In summary, the monophasic course is a frequent and distinct presentation of TBE that is associated with more difficult disease course and higher levels of inflammatory mediators in CSF than the biphasic course; however, the long-term outcome is similar. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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8 pages, 459 KiB

Open AccessCommunication

Comparison of Three Serological Methods for the Epidemiological Investigation of TBE in Dogs

by Philipp Girl, Maja Haut, Sandra Riederer, Martin Pfeffer and Gerhard Dobler

Microorganisms 2021, 9(2), 399; https://doi.org/10.3390/microorganisms9020399 - 15 Feb 2021

Cited by 11 | Viewed by 2235

Abstract

Tick-borne encephalitis (TBE) virus is an emerging pathogen that causes severe infections in humans. Infection risk areas are mostly defined based on the incidence of human cases, a method which does not work well in areas with sporadic TBE cases. Thus, sentinel animals [...] Read more.

Tick-borne encephalitis (TBE) virus is an emerging pathogen that causes severe infections in humans. Infection risk areas are mostly defined based on the incidence of human cases, a method which does not work well in areas with sporadic TBE cases. Thus, sentinel animals may help to better estimate the existing risk. Serological tests should be thoroughly evaluated for this purpose. Here, we tested three test formats to assess the use of dogs as sentinel animals. A total of 208 dog sera from a known endemic area in Southern Germany were tested in an All-Species-ELISA and indirect immunofluorescence assays (IIFA), according to the manufacturer’s instructions. Sensitivity and specificity for both were determined in comparison to the micro-neutralization test (NT) results. Of all 208 samples, 22.1% tested positive in the micro-NT. A total of 18.3% of the samples showed characteristic fluorescence in the IIFA and were, thus, judged positive. In comparison to the micro-NT, a sensitivity of 78.3% and a specificity of 98.8% was obtained. In the ELISA, 19.2% of samples tested positive, with a sensitivity of 84.8% and a specificity of 99.4%. The ELISA is a highly specific test for TBE-antibody detection in dogs and should be well suited for acute diagnostics. However, due to deficits in sensitivity, it cannot replace the NT, at least for epidemiological studies. With even lower specificity and sensitivity, the same applies to IIFA. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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12 pages, 1049 KiB

Open AccessArticle

Low Virus-Specific IgG Antibodies in Adverse Clinical Course and Outcome of Tick-Borne Encephalitis

by Petra Bogovič, Stanka Lotrič-Furlan, Tatjana Avšič-Županc, Miša Korva, Lara Lusa, Klemen Strle and Franc Strle

Microorganisms 2021, 9(2), 332; https://doi.org/10.3390/microorganisms9020332 - 7 Feb 2021

Cited by 9 | Viewed by 2455

Abstract

Tick-borne encephalitis (TBE) is associated with a range of disease severity. The reasons for this heterogeneity are not clear. Levels of serum IgG antibodies to TBE virus (TBEV) were determined in 691 adult patients during the meningoencephalitic phase of TBE and correlated with [...] Read more.

Tick-borne encephalitis (TBE) is associated with a range of disease severity. The reasons for this heterogeneity are not clear. Levels of serum IgG antibodies to TBE virus (TBEV) were determined in 691 adult patients during the meningoencephalitic phase of TBE and correlated with detailed clinical and laboratory parameters during acute illness and with the presence of post-encephalitic syndrome (PES) 2–7 years after TBE. Specific IgG antibody levels ranged from below cut-off value (in 32/691 patients, 4.6%), to 896 U/mL (median = 37.3 U/mL). Patients with meningoencephalomyelitis were more often seronegative (24.3%; 9/37) than those with meningoencephalitis (4.7%; 20/428) or meningitis (1.3%; 3/226). Moreover, patients with antibody levels below cut-off had longer hospitalization (13 versus 8 days); more often required intensive care unit treatment (22% versus 8%) and artificial ventilation (71% versus 21%); and had a higher fatality rate (3/32; 9.4% versus 1/659; 0.2%) than seropositive patients. These results were confirmed when antibody levels, rather than cut-off values, were correlated with clinical parameters including the likelihood to develop PES. Low serum IgG antibody responses against TBEV at the onset of neurologic involvement are associated with a more difficult clinical course and unfavorable long-term outcome of TBE, providing a diagnostic and clinical challenge for physicians. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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10 pages, 559 KiB

Open AccessCommunication

The Stable Matching Problem in TBEV Enzootic Circulation: How Important Is the Perfect Tick-Virus Match?

by Katrin Liebig, Mathias Boelke, Domenic Grund, Sabine Schicht, Malena Bestehorn-Willmann, Lidia Chitimia-Dobler, Gerhard Dobler, Klaus Jung and Stefanie C. Becker

Microorganisms 2021, 9(1), 196; https://doi.org/10.3390/microorganisms9010196 - 19 Jan 2021

Cited by 6 | Viewed by 2530

Abstract

Tick-borne encephalitis virus (TBEV), like other arthropod-transmitted viruses, depends on specific vectors to complete its enzootic cycle. It has been long known that Ixodes ricinus ticks constitute the main vector for TBEV in Europe. In contrast to the wide distribution of the TBEV [...] Read more.

Tick-borne encephalitis virus (TBEV), like other arthropod-transmitted viruses, depends on specific vectors to complete its enzootic cycle. It has been long known that Ixodes ricinus ticks constitute the main vector for TBEV in Europe. In contrast to the wide distribution of the TBEV vector, the occurrence of TBEV transmission is focal and often restricted to a small parcel of land, whereas surrounding areas with seemingly similar habitat parameters are free of TBEV. Thus, the question arises which factors shape this focal distribution of TBEV in the natural habitat. To shed light on factors driving TBEV-focus formation, we used tick populations from two TBEV-foci in Lower Saxony and two TBEV-foci from Bavaria with their respective virus isolates as a showcase to analyze the impact of specific virus isolate-tick population relationships. Using artificial blood feeding and field-collected nymphal ticks as experimental means, our investigation showed that the probability of getting infected with the synonymous TBEV isolate as compared to the nonsynonymous TBEV isolate was elevated but significantly higher only in one of the four TBEV foci. More obviously, median viral RNA copy numbers were significantly higher in the synonymous virus–tick population pairings. These findings may present a hint for a coevolutionary adaptation of virus and tick populations. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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13 pages, 1075 KiB

Open AccessArticle

The Red Fox (Vulpes vulpes) as Sentinel for Tick-Borne Encephalitis Virus in Endemic and Non-Endemic Areas

by Maja Haut, Philipp Girl, Beate Oswald, Thomas Romig, Anna Obiegala, Gerhard Dobler and Martin Pfeffer

Microorganisms 2020, 8(11), 1817; https://doi.org/10.3390/microorganisms8111817 - 18 Nov 2020

Cited by 13 | Viewed by 3242

Abstract

Tick-borne encephalitis (TBE) is one of the most important viral zoonosis caused by a neurotropic arbovirus (TBEV). In Germany, TBE is classified as a notifiable disease with an average of 350 autochthonous human cases annually. The incidence-based risk assessment in Germany came under [...] Read more.

Tick-borne encephalitis (TBE) is one of the most important viral zoonosis caused by a neurotropic arbovirus (TBEV). In Germany, TBE is classified as a notifiable disease with an average of 350 autochthonous human cases annually. The incidence-based risk assessment in Germany came under criticism because every year, a number of autochthonous human TBE cases have been detected outside of the official risk areas. Therefore, it is necessary to find additional parameters to strengthen TBEV surveillance. The aim of this study was to examine red foxes as sentinels for TBE. Thus far, there are no published data about the sensitivity and specificity for serological methods testing fox samples. Hence, we aimed to define a system for the screening of TBEV-specific antibodies in red foxes. A total of 1233 fox sera were collected and examined by ELISA and IIFA and confirmed by micro-NT. The overall seroprevalence of antibodies against TBEV in red foxes from Germany confirmed by micro-NT was 21.1%. The seroprevalence differed significantly between risk (30.5%) and non-risk areas (13.1%), with good correlations to local TBE incidence in humans. In conclusion, serological monitoring of red foxes represents a promising surrogate marker system and may even determine unexpected TBEV foci in regions currently regarded as non-risk areas. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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8 pages, 215 KiB

Open AccessArticle

A Retrospective Epidemiological Study of Tick-Borne Encephalitis Virus in Patients with Neurological Disorders in Hokkaido, Japan

by Kentaro Yoshii, Ikuko Takahashi-Iwata, Shinichi Shirai, Shintaro Kobayashi, Ichiro Yabe and Hidenao Sasaki

Microorganisms 2020, 8(11), 1672; https://doi.org/10.3390/microorganisms8111672 - 28 Oct 2020

Cited by 9 | Viewed by 2953

Abstract

Tick-borne encephalitis (TBE) is a zoonotic disease that usually presents as a moderate febrile illness followed by severe encephalitis, and various neurological symptoms are observed depending on the distinct central nervous system (CNS) regions affected by the TBE virus (TBEV) infection. In Japan, [...] Read more.

Tick-borne encephalitis (TBE) is a zoonotic disease that usually presents as a moderate febrile illness followed by severe encephalitis, and various neurological symptoms are observed depending on the distinct central nervous system (CNS) regions affected by the TBE virus (TBEV) infection. In Japan, TBE incidence is increasing and TBEV distributions are reported in wide areas, specifically in Hokkaido. However, an extensive epidemiological survey regarding TBEV has not been conducted yet. In this study, we conducted a retrospective study of the prevalence of antibodies against TBEV in patients with neurological disorders and healthy populations in a TBEV-endemic area in Hokkaido. Among 2000 patients, three patients with inflammatory diseases in the CNS had TBEV-specific IgM antibodies and neutralizing antibodies. The other four patients diagnosed clinically with other neurological diseases were positive for TBEV-specific IgG and neutralizing antibodies, indicating previous TBEV infection. In a total of 246 healthy residents in a TBEV-endemic region, one resident had TBEV-specific antibodies. These results demonstrated undiagnosed TBEV infections in Japan. Further surveys are required to reveal the actual epidemiological risk of TBE and to consider preventive measures, such as a vaccine program, for the control of TBE in Japan. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

12 pages, 2979 KiB

Open AccessArticle

Baltic Group Tick-Borne Encephalitis Virus Phylogeography: Systemic Inconsistency Pattern between Genetic and Geographic Distances

by Andrei A. Deviatkin, Ivan S. Kholodilov, Oxana A. Belova, Sergey V. Bugmyrin, Lubov A. Bespyatova, Anna Y. Ivannikova, Yulia A. Vakulenko, Alexander N. Lukashev and Galina G. Karganova

Microorganisms 2020, 8(10), 1589; https://doi.org/10.3390/microorganisms8101589 - 15 Oct 2020

Cited by 5 | Viewed by 3186

Abstract

Tick-Borne Encephalitis Virus (TBEV) is a dangerous arbovirus widely distributed in Northern Eurasia. The area of this pathogen changes over time. At the beginning of the 2000s, the Ixodes tick populations in Karelia increased. At the same time, the area of I. persulcatus [...] Read more.

Tick-Borne Encephalitis Virus (TBEV) is a dangerous arbovirus widely distributed in Northern Eurasia. The area of this pathogen changes over time. At the beginning of the 2000s, the Ixodes tick populations in Karelia increased. At the same time, the area of I. persulcatus, the main vector of the Siberian TBEV subtype, also expanded. Herein, we sequenced 10 viruses isolated from ticks collected in three locations from the Karelia region in 2008–2018. PCR positive samples were passaged in suckling mice or pig embryo kidney cells (PEK). After the second passage in suckling, mice viral RNA was isolated and E-gene fragment was sequenced. Viral sequences were expected to be similar or nearly identical. Instead, there was up to a 4.8% difference in nucleotide sequence, comparable with the most diverse viruses belonging to the Baltic subgroup in Siberian TBEV subtype (Baltic TBEV-Sib). To reveal whether this was systemic or incidental, a comprehensive phylogeographical analysis was conducted. Interestingly, viruses within each geographic region demonstrated comparable diversity to the whole Baltic TBEV-Sib. Moreover, Baltic TBEV-Sib has a distribution area limited by three ecological regions. This means that active virus mixing occurs in the vast geographic area forming one common virus pool. The most plausible explanation is the involvement of flying animals in the TBEV spread. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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12 pages, 6602 KiB

Open AccessArticle

Tick-Borne Encephalitis Virus and Its European Distribution in Ticks and Endothermic Mammals

by Melanie Walter, Janna R. Vogelgesang, Franz Rubel and Katharina Brugger

Microorganisms 2020, 8(7), 1065; https://doi.org/10.3390/microorganisms8071065 - 17 Jul 2020

Cited by 19 | Viewed by 4393

Abstract

Tick-borne encephalitis (TBE) is the most common viral tick-borne disease in Europe causing thousands of human infections every year. Available risk maps in Europe are solely based on human incidences, but often underestimate areas with TBE virus circulation as shown by several autochthonous [...] Read more.

Tick-borne encephalitis (TBE) is the most common viral tick-borne disease in Europe causing thousands of human infections every year. Available risk maps in Europe are solely based on human incidences, but often underestimate areas with TBE virus circulation as shown by several autochthonous cases detected outside known risk areas. A dataset of more than 1300 georeferenced TBE virus detections in ticks and mammals except for humans was compiled and used to estimate the probability of TBE virus presence in Europe. For this, a random forests model was implemented using temperature- and precipitation-dependent bioclimatic variables of the WorldClim dataset, altitude, as well as land cover of the ESA GlobCover dataset. The highest probabilities of TBE virus presence were identified in Central Europe, in the south of the Nordic countries, and in the Baltic countries. The model performance was evaluated by an out-of-bag error (OOB) of 0.174 and a high area under the curve value (AUC) of 0.905. The TBE virus presence maps may subsequently be used to estimate the risk of TBE virus infections in humans and can support decision-makers to identify TBE risk areas and to encourage people to take appropriate actions against tick bites and TBE virus infections. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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4 pages, 215 KiB

Open AccessCase Report

Tick-Borne Encephalitis in an 8.5-Month-Old Boy Suspected of Febrile Seizures

by Lenka Krbková, Iva Čapovová, Lukáš Homola, Jana Lindušková, Jiří Salát and Daniel Růžek

Microorganisms 2021, 9(7), 1425; https://doi.org/10.3390/microorganisms9071425 - 1 Jul 2021

Cited by 4 | Viewed by 2350

Abstract

Tick-borne encephalitis (TBE) is a serious viral neuroinfection affecting humans in large areas of Europe and Asia. TBE can occur at any age, but only a few reports of TBE in infants younger than 1 year have been published. Here, we report a [...] Read more.

Tick-borne encephalitis (TBE) is a serious viral neuroinfection affecting humans in large areas of Europe and Asia. TBE can occur at any age, but only a few reports of TBE in infants younger than 1 year have been published. Here, we report a case of severe TBE in an 8.5-month-old boy presenting with seizures at the beginning of the neurological phase. Full article

(This article belongs to the Special Issue Tick-Borne Encephalitis)

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