Comparison of whole genomes of tick-borne encephalitis virus from mountainous alpine regions and regions with a lower altitude.

Tick-borne encephalitis (TBE) has been a notifiable disease in Germany since 2001. Its causative agent, the TBE virus (TBEV), is the most important arbovirus in Europe and Northern Asia. The illness, caused by the European Subtype usually displays flu-like symptoms, but can result in sequelae and, in 2 % of all cases, in death. Over the last few decades, the virus has spread into new habitats, such as higher altitudes in the Alpine region. For this study, it was hypothesized that the environmental challenges that the virus might be exposed to at such altitudes could lead to the selection of viral strains with a higher resilience to such environmental factors. To determine whether strains identified at higher altitudes possessed different genetic traits compared to viruses from lower altitudes, an analysis of viral genomes from higher Alpine altitudes (> 500 m above sea level) (n = 5) and lower altitudes (< 500 m above sea level) (n = 4) was performed. No common phylogenetic ancestry or shared amino acid substitutions could be identified that differentiated the alpine from the lowland viral strains. These findings support the idea of many individual introductions of TBEV into the alpine region and the establishment of foci due to non-viral specific factors such as favorable conditions for vector species and host animals due to climate change.

Tick-Borne Encephalitis Virus Nonstructural Protein 1 IgG Enzyme-Linked Immunosorbent Assay for Differentiating Infection versus Vaccination Antibody Responses.

Tick-borne encephalitis virus (TBEV) is an important central nervous system (CNS) infection in Europe and Asia. It is a flavivirus in the tick-borne group. Effective vaccines against TBE are available in the affected countries. However, diagnosing TBE is challenging due to cross-reactive antibodies between different viruses of the genus Flavivirus, family Flaviviridae. Differentiation between infection-induced and vaccine-induced antibodies can be difficult and in many cases impossible, due to the increasing vaccination rate against TBEV. We present a new approach to detect antibodies against the TBEV nonstructural protein 1 (NS1) as a diagnostic marker, which is exclusively indicative for virus replication in natural infection, on the basis of an enzyme-linked immunosorbent assay (ELISA). A total of 188 anonymous serum samples from the National Consultant Laboratory for TBEV were included in our study. The assay was validated according to the European Laboratory Norm DIN EN ISO 15189 for diagnostic use. The ELISA for the detection of TBEV NS1 specific IgG class antibodies has demonstrated a sensitivity of >94% and a specificity of >93% in broadly cross-reacting sera from patients with vaccinations against flaviviral diseases and single or multiple flavivirus infections, respectively. The detection of anti-NS1 antibodies is feasible and facilitates reliable differentiation between different flavivirus infections, TBEV infection, and TBE vaccination.

Tick-borne encephalitis virus vaccination breakthrough infections in Germany: a retrospective analysis from 2001 to 2018.

OBJECTIVES: There are few data available regarding the clinical course of tick-borne encephalitis virus (TBEV) vaccination breakthrough infections. The published studies suggest that vaccination breakthrough infections may have a more severe course than native TBEV infection in unvaccinated individuals-potentially due to antibody-dependent enhancement. Here we report a large analysis of vaccination breakthrough infections. METHODS: This retrospective analysis was based on a national surveillance dataset spanning the years 2001-2018. Variables reflecting disease severity, such as 'CNS symptoms', 'myelitis', 'fatal outcome' and 'hospitalization' were analysed as well as general epidemiological variables. Cases were categorized as 'unvaccinated' or 'ever vaccinated', the latter category including cases with at least one dose of a TBEV vaccine. RESULTS: A total of 6073 notified TBEV infection cases were included in our analysis. Sufficient data on vaccination status were available for 95.1% of patients (5777/6073); of these, 5298 presented with a native infection. A total of (334/5777) cases developed an infection despite having been vaccinated at least once. Comparing unvaccinated patients with those with at least one vaccination, we find an odds ratio (OR) 2.73, (95% confidence interval (CI) 0.79-9.50) regarding the variable fatal outcome that did not reach statistical significance. Analysing the clinical variables 'CNS symptoms' and 'myelitis', there is no difference between these groups (OR 0.86, 95% CI 0.68-1.08; and OR 1.30, 95% CI 0.74-2.27 respectively). Patients who were vaccinated and had an assumed protection at symptom onset (n = 100) had a higher risk for the development of myelitic symptoms (OR 2.21, 95% CI 1.01-4.86]) than unvaccinated patients. CONCLUSION: Our findings could neither verify that vaccination breakthrough infections might cause a more severe disease than native infections nor prove a clear antibody-dependent enhancement phenomenon. It remains unclear whether the increased myelitis risk in a subgroup of vaccinated patients is a true effect or confounded.

A cluster of two human cases of tick-borne encephalitis (TBE) transmitted by unpasteurised goat milk and cheese in Germany, May 2016.

In May 2016, two cases of tick-borne encephalitis (TBE) were confirmed by serology (positive IgM and IgG antibodies against TBE virus (TBEV) in serum), with a possible link to raw milk and cheese from a goat farm in a region in Baden-Württemberg, Germany not previously known as TBE-endemic. The outbreak investigation identified 32 consumers of goat dairy products (29 consumers, one farm employee, two owners) of whom none had IgM antibodies against TBEV 3-8 weeks after consumption. Of the 27 notified TBE cases in the State, none reported consumption of raw goat milk or cheese from the suspected farm. Five of 22 cheese samples from 18 different batches were RT-qPCR-positive for TBEV -genome, and two of the five samples were confirmed by virus isolation, indicating viability of TBEV in the cheese. Nine of the 45 goats had neutralising TBEV antibodies, two of them with a high titre indicating recent infection. One of 412 Ixodes ricinus was RT-qPCR-positive, and sequencing of the E gene from nucleic acid extracted from the tick confirmed TBEV. Phylogenetic analyses of tick and cheese isolates showed 100% amino acid homology in the E gene and a close relation to TBEV strains from Switzerland and Austria.

Complete Genome Sequence of a Low-Virulence Tick-Borne Encephalitis Virus Strain.

We report here the complete genome sequence (GenBank accession no. KX268728) of tick-borne encephalitis strain HB171/11, isolated from an Ixodes ricinus tick from a natural focus where human neurological disease is rare. The strain shows unique characteristics in neuroinvasiveness and neurovirulence.

[Threat of transmission of infectious pathogens by Ixodes ricinus ticks in Germany]. / Gefahren der Übertragung von Krankheitserregern durch Schildzecken in Deutschland.

Tick-transmitted diseases are of great importance for the general health of the German population. Several viruses, such as tick-borne encephalitis virus (TBEV), Uukuniemi virus, Tribec virus, Eyach virus or bacteria, such as Borrelia, Rickettsiae, Francisella tularensis, Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis (CNM) and Coxiella burnetii were detected in the most prominent tick in Germany, the hard tick Ixodes ricinus. While infections, such as TBE and Lyme disease are well known, other infections are hardly known even among experts. Although there have been a few descriptions of isolated cases in Germany, a systematic investigation regarding the distribution and the pathogenic potential of these pathogens is still lacking. In particular elderly people and people with underlying diseases seem to be mostly affected. The importance of new infectious disease agents, such as Candidatus Neoehrlichia mikurensis but also of long known pathogens, such as Rickettsiae still remains unclear, while some of them could be detected in 20 % of investigated ticks. Whether climate change contributes to the further distribution of these infectious agents remains unclear and requires further investigation. The increasing initiatives to create natural environments and the trend towards spending more time in nature for recreational activities will increase the danger of coming into contact with ticks and the respective infectious agents. Considering these circumstances an increase of diseases caused by these pathogens is to be expected.

Spotted fever group--Rickettsiae in the Tyrols: evidence by seroepidemiology and PCR.

The aim of our study was to assess the occurrence of Rickettsia in the inner-alpine valleys of the Eastern Alps and to determine the amount of seroreaction among the local human population. Ticks were investigated by PCR and the percentage of seropositives was determined among local blood donors by an in-house immunofluorescence assay. The local cut-off titre for screening of IgG was set at 1 : 128 with a well-characterised low-risk collective according to WHO-guidelines. Positive sera were confirmed by independent re-testing. Rickettsia is present in ticks north and south of the continental divide. Of 259 ticks investigated, 12.4% are positive for Rickettsia. Of over 1200 blood donors tested so far, 7.7% bear IgG at a titre of 1 : 128 or higher against R. helvetica. R. helvetica is present in the study area, causes immunoreaction among local residents and is associated with anamnestic erythema. Furthermore, screening with a second Spotted Fever Group Rickettsia indicates that significant parts of the Tyrolean population are exposed to a Rickettsia other than R. helvetica.

Virus detection in questing ticks is not a sensitive indicator for risk assessment of tick-borne encephalitis in humans.

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted arbovirus causing human disease in Europe, but information on its endemic occurrence varies between countries because of differences in surveillance systems. Objective data are necessary to ascertain the disease risk for vaccination recommendations and other public health interventions. In two independent, separately planned projects, we used real-time RT-PCR to detect TBE virus in questing ticks. In Poland, 32 sampling sites were selected in 10 administrative districts located in regions where sporadic TBE cases were reported. In Germany, 18 sampling sites were selected in two districts located in a region with high TBE incidence. Altogether, >16,000 ticks were tested by real-time RT-PCR, with no sample testing positive for TBEV. A systematic search for published studies on TBEV prevalence in ticks in Poland and Germany also suggested that testing large numbers of collected ticks could not consistently assure virus detection in known endemic foci. Although assignment of results to administrative regions is essential for TBE risk mapping, this was possible in only 10 (investigating 22,417 ticks) of 15 published studies (>50,000 ticks) identified. We conclude that the collection and screening of ticks by real-time RT-PCR cannot be recommended for assessment of human TBE risk. Alternative methods of environmental TBEV monitoring should be considered, such as serological monitoring of rodents or other wildlife.

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.

Chikungunya fever in two German tourists returning from the Maldives, September, 2009.

This report describes the first isolation and molecular characterisation of a chikungunya virus from two German tourists who became ill after a visit to the Maldives in September 2009. The virus contained the E1 A226V mutation, shown to be responsible for an adaptation to the Asian tiger mosquito Aedes albopictus. The E1 coding sequence was identical to chikungunya virus isolates from Sri Lanka and showed three nt-mismatches to the only available E1 nt sequence from the Maldives.

[Severe tick-borne encephalomyelitis with lack of cerebrospinal fluid pleocytosis]. / Schwere Frühsommer-Meningo-Enzephalomyelitis ohne Liquor-Pleozytose.

Tick borne encephalitis (TBE) is an important viral encephalitis in central and eastern Europe. Cerebrospinal fluid (CSF) pleocytosis has been described in all published patients so far. This may be due to selection bias, however, as CSF pleocytosis is often used as a case definition parameter. The frequency of TBE without CSF pleocytosis is unknown. We report two cases who developed severe TBE without CSF pleocytosis. A normal CSF cell count should therefore not discourage from the differential diagnosis of TBE and deter from serological testing in patients with a clinical constellation suggesting TBE.

Imported aseptic meningitis due to Toscana virus acquired on the island of Elba, Italy, August 2008.

We describe a case of aseptic meningitis due to Toscana Virus imported to Switzerland and discuss the epidemiological situation. To our knowledge this is the first description of this infection acquired on the Island of Elba.

Rickettsia spp. in Ixodes ricinus ticks in Bavaria, Germany.

This study aims to provide information on the occurrence of spotted fever rickettsiae in Ixodes ricinus ticks in southern Germany. A total of 2,141 I. ricinus ticks was collected in Bavaria. Pools of 5-10 ticks were studied by a PCR targeting the rickettsial citrate synthase gene gltA. The average prevalence rate was 12% (257 of 2,141). Sequencing data exclusively identified Rickettsia helvetica DNA. Results and other data demonstrate the possible role of R. helvetica in I. ricinus as a source of human infections in southern Germany.

A new Puumala hantavirus subtype in rodents associated with an outbreak of Nephropathia epidemica in South-East Germany in 2004.

A micro-epidemic of hantavirus infections occurred in Lower Bavaria, South-East Germany, starting in April 2004. While only three cases were registered from 2001 to 2003, a dramatically increased number of clinically apparent human hantavirus infections (n=38) was observed in 2004, plus seven additional cases by June 2005. To determine the reservoir responsible for the infections, a total of 43 rodents were trapped in Lower Bavaria. Serological and genetic investigations revealed that Puumala virus (PUUV) is dominant in the local population of bank voles. Partial PUUV S segment nucleotide sequences originating from bank voles at four different trapping sites in Lower Bavaria showed a low divergence (up to 3.1%). This is contrasted by a nucleotide sequence divergence of 14-16% to PUUV strains detected in Belgium, France, Slovakia or North-Western Germany. PUUV sequences from bank voles in Lower Bavaria represent a new PUUV subtype which seems to be responsible for the observed increase of human hantavirus infections in 2004-2005.

[The elderly traveler]. / Reiseberatung für Senioren ist mehr als eine Hepatitisimpfung. Wohin darf Ihr Rentner fliegen?

In recent years, the number of senior citizen travelers has been increasing. As a result of this trend, the general practitioner is every more frequently being confronted with the problem of counseling his elderly patients. A particularly important point is that underlying illnesses and long-term medication must be adapted to the destination, traveling time and style of traveling. Since considerable immunization deficits can be found among senior citizens, the application of prophylactic vaccination prior to the jou rney presents an ideal opportunity to bring the patient's immunization status up to date in terms of generally recommended vaccinations. Should chemoprophylaxis be necessary, consideration must always be given to drug interactions. By making appropriate recommendations in terms of health-related and destination-related dos and don'ts, the risk of developing health problems while traveling can be minimized.