What we know and still do not know about tick-borne encephalitis?

Tick-borne encephalitis (TBE) is a febrile illness caused by tick-borne encephalitis virus (TBEV), frequently manifesting as inflammation of the central nervous system. TBEV is a typical arbovirus, i.e., belongs to a group of viruses transmitted by blood-sucking arthropods. Taxonomically, TBEV is a member of the genus Flavivirus, family Flaviviridae. The disease is endemic in North Eurasia, from western Europe to East Asia. The virus occurs in natural foci of the disease all over Czechia, where it is transmitted predominantly by the castor bean tick (Ixodes ricinus). This infection has a potential to cause significant long-term disability affecting the quality of the patients life. Vaccine is available; however, vaccination coverage in Czechia is still low (around 30% of the total population). Lately, attention has been focused on new possibilities for early diagnosis and specific treatment, which so far has only been symptomatic or empirical.

Tick-borne encephalitis in domestic animals.

Tick-borne encephalitis (TBE), a disease caused by tick-borne encephalitis virus (TBEV), represents a serious neural infection of humans in Europe and Asia. The main reservoir hosts of TBEV are ticks, rodents and insectivores, but domestic animals may also be infected with the virus. This review summarizes what is known about TBE in domestic species (e.g., dogs, horses), in which infection may manifest with clinical signs similar to those seen in severe human cases. We also focus on TBE in ruminants where TBE infections are typically asymptomatic and do not cause health problems in the infected hosts. However, the risk to human health is the main problem of asymptomatic infection, because the presence of TBEV in the milk of infected ruminants can serve as a source of TBE infection via the alimentary route. An experimental veterinary vaccine was developed recently, and future vaccination of selected domestic animals is proposed to avoid the development of severe TBE symptoms in sensitive animals (e.g., dogs, horses) or to decrease the risk of alimentary infection in humans (e.g., goats and sheep). Keywords: tick-borne encephalitis; dog; goat; sheep; cow; horse.

A comparative analysis on the physicochemical properties of tick-borne encephalitis virus envelope protein residues that affect its antigenic properties.

This work is dedicated to the study of the variability of the main antigenic envelope protein E among different strains of tick-borne encephalitis virus at the level of physical and chemical properties of the amino acid residues. E protein variants were extracted from then NCBI database. Four amino acid residues properties in the polypeptide sequences were investigated: the average volume of the amino acid residue in the protein tertiary structure, the number of amino acid residue hydrogen bond donors, the charge of amino acid residue lateral radical and the dipole moment of the amino acid residue. These physico-chemical properties are involved in antigen-antibody interactions. As a result, 103 different variants of the antigenic determinants of the tick-borne encephalitis virus E protein were found, significantly different by physical and chemical properties of the amino acid residues in their structure. This means that some strains among the natural variants of tick-borne encephalitis virus can potentially escape the immune response induced by the standard vaccine.

Comparative analysis of complete genome sequences of European subtype tick-borne encephalitis virus strains isolated from Ixodes persulcatus ticks, long-tailed ground squirrel (Spermophilus undulatus), and human blood in the Asian part of Russia.

Tick-borne encephalitis virus (TBEV) is divided into three subtypes: European (TBEV-Eu), Siberian (TBEV-Sib), and Far Eastern (TBEV-FE) subtypes. The geographical range of TBEV-Eu dominates in Europe, but this subtype is present focally across the whole non-tropical forested Eurasian belt, through Russia to South Korea. However, the TBEV-Eu strains isolated outside Europe remain poorly characterized. In this study, full-genome sequences of eight TBEV-Eu isolates were determined. These strains were isolated from Ixodes persulcatus ticks, long-tailed ground squirrel (Spermophilus undulatus), and human blood in the natural foci of Western and Eastern Siberia, Russia. A phylogenetic analysis of all available TBEV-Eu genomic sequences revealed that strains from Siberia were closely related to other strains from Europe and South Korea. The closest relation was identified between the Siberian strains and strains from Zmeinogorsk (Western Siberia, Russia) and strain Absettarov (Karelia, Russia), and were most divergent from strains from the Czech Republic and Norway. TBEV-Eu strains isolated in Eastern Siberia were more closely related phylogenetically to strains from South Korea, but strains from Western Siberia grouped together with the strains from Europe, suggesting two genetic TBEV-Eu lineages present in Siberia.

The occurrence of Ixodes ricinus ticks and important tick-borne pathogens in areas with high tick-borne encephalitis prevalence in different altitudinal levels of the Czech Republic Part I. Ixodes ricinus ticks and tick-borne encephalitis virus.

STUDY OBJECTIVE: The aim of the three-year study (2011-2013) was to monitor population density of Ixodes ricinus ticks and its infection rate with the tick-borne encephalitis virus in areas with a high incidence of tick-borne encephalitis as reported in the previous decade 2001-2010. Such a comprehensive and long-term study based on existing epidemiolo-gical findings has not previously been conducted in Europe. MATERIAL AND METHODS: In the areas of the Ústí nad Labem Region, Olomouc Region, South Bohemian Region, and Highlands Region, 600 m2 plots were selected in the local optimal I. ricinus habitats where tick flagging was performed every year in the spring-summer and autumn seasons of the questing activity. In total, 18,721 I. ricinus ticks (1448 females, 1425 males, and 15,848 nymphs) were collected and investigated. RESULTS AND CONCLUSION: The results have shown that the differences in the infection rate of I. ricinus observed between regions are driven by variation in the density of the local I. ricinus populations which is influenced by the characteris-tics of the whole local biocenosis. The overall prevalence estimate of TBE virus in Ixodes ricinus ticks at the altitudes below 600 m a.s.l. was 0.096 % (95% CI 0.055-0.156) for nymphs, and 0.477 % (95% CI 0.272-0.773) for adults. The dynamics of the seasonal variation in I. ricinus populations, depending primarily on the climatic factors, are behind the interyear differences in the infection rate of ticks and, consequently, in the epidemiological situation of tick-borne encephalitis. The nymph to adult ratio was 5.5 on average but showed great interregional variability (from 10.3 in the Ústí nad Labem Region to 1.8 in the Highlands Region). It might be used in the future as one of the indicators of the composition of the local I. ricinus population and of the level of the circulation of tick-borne pathogens in zoonotic sphere and also for use in the health risk assessment in a given area. Despite the permanent expansion of ticks and tick-borne pathogens in higher altitudes the high risk limit for human infection with tick-borne encephalitis is 600 m a.s.l. in the Czech Republic.

[Tick-borne encefalitis - pathogenesis and -therapeutic approaches]. / Patogeneze klístové encefalitidy a moznosti antivirové terapie.

Tick-borne encephalitis (TBE) is a major public health threat in large areas of Central and Eastern Europe and in Russia. This review summarizes the current data on the interactions between the TBE virus and the host, with a particular focus on the mechanisms of neuronal injury, immune response and immunopathology in the central nervous system (CNS), and factors that determine the course and outcome of TBE. Novel trends of experimental therapy of TBE are discussed. Combining small molecule inhibitors targeting viral replication with immunomodulatury agents might be a way to maximize viral clearance and minimize immunopathology in the CNS during TBE.

Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells.

Type I interferon (IFN), mainly produced by dendritic cells (DCs), is critical in the host defence against tick-transmitted pathogens. Here, we report that salivary cysteine protease inhibitor from the hard tick Ixodes scapularis, sialostatin L2, affects IFN-ß mediated immune reactions in mouse dendritic cells. Following IFN receptor ligation, the Janus activated kinases/signal transducer and activator of transcription (JAK/STAT) pathway is activated. We show that sialostatin L2 attenuates phosphorylation of STATs in spleen dendritic cells upon addition of recombinant IFN-ß. LPS-stimulated dendritic cells release IFN-ß which in turn leads to the induction of IFN-stimulated genes (ISG) through JAK/STAT pathway activation. The induction of two ISG, interferon regulatory factor 7 (IRF-7) and IP-10, was suppressed by sialostatin L2 in LPS-stimulated dendritic cells. Finally, the interference of sialostatin L2 with IFN action led to the enhanced replication of tick-borne encephalitis virus in DC. In summary, we present here that tick salivary cystatin negatively affects IFN-ß responses which may consequently increase the pathogen load after transmission via tick saliva.

Detection panel for identification of twelve hemorrhagic viruses using real-time RT-PCR.

BACKGROUND: Viral hemorrhagic fevers are caused by viruses from four viral families and develop diseases with high fatality rates. However, no commercial diagnostic assay for these pathogens is available. FINDINGS: We developed real-time RT-PCR assays for viruses Ebola, Marburg, Lassa, Guanarito, Machupo, Junin, Sabiá, Seoul, Puumala, Hantaan, Crimean-Congo hemorrhagic fever virus and Rift Valley fever virus. The assays were optimized for identical reaction conditions and can be performed using several types of real-time PCR instruments, both capillary and plate, including a portable Ruggedized Advanced Pathogen Identification Device (R.A.P.I.D.) (Idaho Technology, Inc.). CONCLUSIONS: In combination with primers and probes from previously published studies, we present a simple system for rapid identification of hemorrhagic filoviruses, arenaviruses and bunyaviruses with sufficient sensitivity for first contact laboratory and diagnosis under field conditions.

First documented case of imported tick-borne encephalitis in Australia.

We report a case of tick-borne encephalitis that has not been described before in Australia. The patient was a returned traveller from Russia who had typical manifestations of this infection. Clinical diagnosis was elusive because of the peculiar biphasic nature of the illness and its rarity in Australia. Laboratory diagnosis was also challenging and required testing at a reference laboratory in the Czech Republic because of the unavailability of specific assays in Australia. This report aims to make physicians from non-endemic regions aware that tick-borne encephalitis can be imported and to familiarise them with its clinical course.

Relation of genetic phylogeny and geographical distance of tick-borne encephalitis virus in central Europe.

Tick-borne encephalitis virus (TBEV) is the most important arboviral agent causing disease of the central nervous system in central Europe. In this study, 61 TBEV E gene sequences derived from 48 isolates from the Czech Republic, and four isolates and nine TBEV strains detected in ticks from Germany, covering more than half a century from 1954 to 2009, were sequenced and subjected to phylogenetic and Bayesian phylodynamic analysis to determine the phylogeography of TBEV in central Europe. The general Eurasian continental east-to-west pattern of the spread of TBEV was confirmed at the regional level but is interlaced with spreading that arises because of local geography and anthropogenic influence. This spread is reflected by the disease pattern in the Czech Republic that has been observed since 1991. The overall evolutionary rate was estimated to be approximately 8×10(-4) substitutions per nucleotide per year. The analysis of the TBEV E genes of 11 strains isolated at one natural focus in zdár Kaplice proved for the first time that TBEV is indeed subject to local evolution.

High variability in viral load in cerebrospinal fluid from patients with herpes simplex and varicella-zoster infections of the central nervous system.

Infections of the central nervous system (CNS) caused by herpes viruses can result in severe diseases, often with a fatal outcome. In this study, the viral load in the cerebrospinal fluid (CSF) of patients with herpes simplex or varicella-zoster infections of the CNS was measured using a quantitative real-time PCR. The results suggest a high variability in viral load, with relatively mild disease associated with a high viral load in CSF and vice versa. Determination of the viral load in CSF does not therefore seem to be useful in assessing the prognosis of disease caused by these viruses.