Defining the “Correlate(s) of Protection” to tick-borne encephalitis vaccination and infection – key points and outstanding questions

Tick-borne Encephalitis (TBE) is a severe disease of the Central Nervous System (CNS) caused by the tick-borne encephalitis virus (TBEV). The generation of protective immunity after TBEV infection or TBE vaccination relies on the integrated responses of many distinct cell types at distinct physical locations. While long-lasting memory immune responses, in particular, form the basis for the correlates of protection against many diseases, these correlates of protection have not yet been clearly defined for TBE. This review addresses the immune control of TBEV infection and responses to TBE vaccination. Potential correlates of protection and the durability of protection against disease are discussed, along with outstanding questions in the field and possible areas for future research

Fatal Outcome of Tick-borne Encephalitis after Vaccine Failure

Tick-borne encephalitis is a viral disease affecting the central nervous system. It is endemic in Switzerland with 200 to 250 notified cases annually. Active immunization is effective for persons in all age groups. Vaccine failure is rare, in particular after a completed vaccination course. Here, we describe the case of 67-year-old man with a fatal outcome despite vaccination. The diagnosis was confirmed by extensive postmortem analyses. The diagnostic challenges of vaccine failure in tick-borne encephalitis and the dynamics of the immune response in vaccination breakthrough are discussed

Population genomics of Francisella tularensis subsp. holarctica and its implication on the eco-epidemiology of tularemia in Switzerland

Whole genome sequencing (WGS) methods provide new possibilities in the field of molecular epidemiology. This is particularly true for monomorphic organisms where the discriminatory power of traditional methods (e.g., restriction enzyme length polymorphism typing, multi locus sequence typing etc.) is inadequate to elucidate complex disease transmission patterns, as well as resolving the phylogeny at high resolution on a micro-geographic scale. In this study, we present insights into the population structure of; Francisella tularensis; subsp.; holarctica; , the causative agent of tularemia in Switzerland. A total of 59; Fth; isolates were obtained from castor bean ticks (; Ixodes ricinus); , animals and humans and a high resolution phylogeny was inferred using WGS methods. The majority of the; Fth; population in Switzerland belongs to the west European B.11 clade and shows an extraordinary genetic diversity underlining the old evolutionary history of the pathogen in the alpine region. Moreover, a new B.11 subclade was identified which was not described so far. The combined analysis of the epidemiological data of human tularemia cases with the whole genome sequences of the 59 isolates provide evidence that ticks play a pivotal role in transmitting; Fth; to humans and other vertebrates in Switzerland. This is further underlined by the correlation of disease risk estimates with climatic and ecological factors influencing the survival of ticks

Comparison of Four Commercial IgG-Enzyme-Linked Immunosorbent Assays for the Detection of Tick-Borne Encephalitis Virus Antibodies.

Tick-borne encephalitis (TBE) is the most important arboviral disease in many parts of Europe and Asia. Both the diagnosis of TBE as well as the conduction of surveillance studies are based on the demonstration of specific antibodies. For reasons of simplicity, automatization, and quick availability of test results, enzyme-linked immunosorbent assays (ELISAs) are the method of choice for anti-TBE virus antibody detection. In this study, we evaluated four commercial IgG-ELISAs using 876 epidemiological plasma samples: the Enzygnost Anti-TBE/FSME Virus IgG assay (Siemens; assay 1), the Anti-FSME/TBE Virus ELISA (IgG) assay (Euroimmun; assay 2), the Anti-FSME/TBE Virus ELISA "Vienna" (IgG) assay (Euroimmun; assay 3), and the RIDASCREEN FSME/TBE IgG EIA assay (R-Biopharm; assay 4). In total, discrepant results were observed for 37.2% of all samples. The evaluated assays significantly differed in qualitative data (p < 0.0001, Cochran-Mantel-Haenszel test) and showed Spearman's rank correlation coefficients ranging between 0.88 and 0.97 for quantitative data. The degree of disagreement between the different assays was exceptionally high for samples originating from blood donors with vaccination against TBE virus. For this sample group, the proportion of positive results was considerably higher for assay 3 (52.7%) and assay 4 (57%) than for assay 1 (7.5%) and assay 2 (6.4%), respectively, indicating that assays 1 and 2 are less suitable for the detection of vaccination antibodies than assays 3 and 4. Indirect immunofluorescence testing data available for a subset of samples (n = 238) mostly originating from nonflavivirus-vaccinated blood donors (n = 234) revealed problems in both sensitivity and specificity of the evaluated assays; whereas sensitivity issues were most prominent for the Euroimmun assay, specificity concerns were most pronounced for the Euroimmun Vienna and the RIDASCREEN assays

Evaluation of antivirals against tick-borne encephalitis virus in organotypic brain slices of rat cerebellum.

Neurotropic tick borne encephalitis virus (TBEV) causes life-threatening disease, and accounts for most cases of tick-transmitted viral infections in Central and Eastern Europe and Russia. No specific treatment for TBEV infections exists, and vaccination is recommended for people at risk. So far, various nucleoside analogues have been investigated in vitro as potential candidates for treatment of TBEV infections. However, in vitro experiments with more complex cell culture systems, such as organotypic culture slices which model the sophisticated architecture of the target tissue are lacking. Using TBEV as a model, we investigated the suitability of rat organotypic cerebellum slices (OCS) to study the effectiveness of nucleoside analogues with a well-known anti-TBEV activity. In these OCS, 50 μM of the nucleoside analogues 2'-C-methyladenosine (2'-CMA) and especially 7-deaza-2'-C-methyladenosine (7-deaza-2'-CMA) exhibited strong inhibitory effects on TBEV replication, reducing viral titers to an average of 103-fold and TBEV RNA content 60-90-fold. In contrast, the influence of 2'-C-methylcytidine (2'-CMC) on TBEV replication was very weak, reducing virus titers by 10-fold and TBEV RNA content by 3-fold. In agreement with other studies, there was no noticeable difference in TBEV titers between OCS treated with 50 μM of Ribavirin and the DMSO treated controls. All tested nucleoside analogues exhibited excellent cytotoxicity profiles at concentrations of 50 μM. Our findings in OCS were highly comparable to data obtained in cell line culture systems. Therefore, OCS represent an ideal in vitro approach to study antivirals against TBEV and possibly other neurotropic viruses

Population Genomics of Francisella tularensis subsp. holarctica and its Implication on the Eco-Epidemiology of Tularemia in Switzerland

Whole genome sequencing (WGS) methods provide new possibilities in the field of molecular epidemiology. This is particularly true for monomorphic organisms where the discriminatory power of traditional methods (e.g., restriction enzyme length polymorphism typing, multi locus sequence typing etc.) is inadequate to elucidate complex disease transmission patterns, as well as resolving the phylogeny at high resolution on a micro-geographic scale. In this study, we present insights into the population structure of Francisella tularensis subsp. holarctica, the causative agent of tularemia in Switzerland. A total of 59 Fth isolates were obtained from castor bean ticks (Ixodes ricinus), animals and humans and a high resolution phylogeny was inferred using WGS methods. The majority of the Fth population in Switzerland belongs to the west European B.11 clade and shows an extraordinary genetic diversity underlining the old evolutionary history of the pathogen in the alpine region. Moreover, a new B.11 subclade was identified which was not described so far. The combined analysis of the epidemiological data of human tularemia cases with the whole genome sequences of the 59 isolates provide evidence that ticks play a pivotal role in transmitting Fth to humans and other vertebrates in Switzerland. This is further underlined by the correlation of disease risk estimates with climatic and ecological factors influencing the survival of ticks

Hantavirus Cardiopulmonary Syndrome Due to Imported Andes Hantavirus Infection in Switzerland: A Multidisciplinary Challenge, Two Cases and a Literature Review.

Two travellers returning from South America were diagnosed with Andes hantavirus infection, the only member of the Hantaviridae family known to be transmitted from person to person. We describe the clinical course and therapeutic and infection control measures. While both patients showed high viral load (VL) and shedding over several months, 1 patient recovered within 1 week from severe respiratory illness that required noninvasive ventilation, whereas the second patient developed severe hantavirus cardiopulmonary syndrome that required extracorporeal membrane oxygenation for 27 days. The clinical course in the latter patient was complicated by severe disseminated intravascular coagulopathy with diffuse hemorrhage that necessitated mass transfusions, as well as by multiple organ failure, including the need for renal replacement therapy. Results of VL in blood, respiratory secretions, and semen for the first 9 months of follow-up are reported. To our knowledge, these are the first cases of Andes hantavirus infection detected in Europe

La Charente

12 janvier 18861886/01/12 (A15,N5451)-1886/01/12.Appartient à l’ensemble documentaire : PoitouCh

Virucidal activity of three standard chemical disinfectants against Ebola virus suspended in tripartite soil and whole blood

Abstract Proper disinfection and inactivation of highly pathogenic viruses is an essential component of public health and prevention. Depending on environment, surfaces, and type of contaminant, various methods of disinfection must be both efficient and available. To test both established and novel chemical disinfectants against risk group 4 viruses in our maximum containment facility, we developed a standardized protocol and assessed the chemical inactivation of the two Ebola virus variants Mayinga and Makona suspended in two different biological soil loads. Standard chemical disinfectants ethanol and sodium hypochlorite completely inactivate both Ebola variants after 30 s in suspension at 70% and 0.5% v/v, respectively, concentrations recommended for disinfection by the World Health Organization. Additionally, peracetic acid is also inactivating at 0.2% v/v under the same conditions. Continued vigilance and optimization of current disinfection protocols is extremely important due to the continuous presence of Ebola virus on the African continent and increased zoonotic spillover of novel viral pathogens. Furthermore, to facilitate general pandemic preparedness, the establishment and sharing of standardized protocols is very important as it allows for rapid testing and evaluation of novel pathogens and chemical disinfectants