Tick-borne Encephalitis Infection Research Articles

Tick-borne encephalitis seroprevalence in northern Italy: a cross-sectional study on a randomly selected population

ObjectivesIxodes ricinus is under-recognized in Europe. This study aimed to determine the seroprevalence and spatial distribution of tick-borne encephalitis (TBE) virus (TBEV) in areas close to endemic regions in Northern Italy. MethodsA multicenter study was conducted on a random sample of the general population afferent to hospitals in Veneto, Lombardy, and Piedmont with a pre-determined sample size of 1500 participants. The presence of TBEV-neutralizing antibodies was determined for sera positive to the TBE‐specific immunoglobulin G test in a centralized laboratory. ResultsOut of 1537 samples analyzed (790 from Lombardy, 394 from Veneto, 353 from Piedmont), 39 (2.5%) were immunoglobulin G TBEV–positive. The frequency of positive cases was similar amid the regions (24-3.0% Lombardy, 10-2.5% Veneto, and 5-1.4% Piedmont; P = 0.27). The seropositivity rates were 3.6% in subjects aged over 50 years, 2.0% in those aged 30-50 years, and 1.5% in subjects aged under 30 years (P = 0.10). Two of them (one from Veneto and one from Lombardy) were confirmed by TBEV neutralization test (prevalence 130 per 100,000). One lived close to an endemic area (Treviso); the other spent time in an endemic region (Friuli) and did not remember experiencing tick bites. ConclusionsThe results from this study highlight the need for raising awareness among the population and health care workers to limit the risk of TBE infection.

First clinical case of tick-borne encephalitis (TBE) in a dog in Greece

Tick-borne encephalitis virus (TBEV) causes tick-borne encephalitis (TBE), affecting human health in Europe and Asia. Reports on canine clinical cases of TBE are rare, although dogs are used as sentinels for assessing human health risks. The first canine clinical TBE case in Greece is reported in this case report. The dog had a history of tick infestation and displayed neurological symptoms, particularly tetraparesis, neck hyperalgesia, and a sudden behavior change. Serum samples were obtained and examined in a commercial ELISA to detect anti-TBEV specific IgG and IgM antibodies. The dog tested seropositive for both IgG and IgM, and based on its history and compatible clinical signs, the diagnosis of TBE infection was reached. The prognosis was initially poor, and treatment included the administration of fluids, corticosteroids, and antibiotics, followed by physical therapy. After a 10-day hospitalization, the dog had a much better prognosis. This case highlights that TBEV does emerge in new locations, increasing human and animal infection risk. Veterinarians should include TBE in their differential diagnosis of canine patients with a history of tick infestations, progressive neurological symptoms, and abnormal behavior.

Заболеваемость клещевым энцефалитом в Центральном федеральном округе России. Клинические случаи тяжелого течения заболевания у детей

This study shows the epidemiological situation of tick-borne encephalitis (TBE) in the regions of the Central Federal District (CFD) of Russia for 2008-2020, including the morbidity in different age groups, children and adolescents. The highest rate was recorded in the Kostroma region – 5.43 ± 0.78 per 100 thousand population, followed by the Yaroslavl and Tver regions – 1.03 ± 0.21 and 0.49 ± 0.08 per 100 thousand, respectively. The incidence tends to decrease, which is more pronounced in the Yaroslavl region. The proportion of children and adolescents among patients with TBE in the Central Federal District regions is 5–11.3%. In the Yaroslavl region, mostly townspeople get sick, in the Kostroma region – rural residents. The structure of clinical forms of TBE in both regions is dominated by febrile forms, however, the proportion of focal forms remains high – over 15% and the proportion of meningeal forms decreases. In Moscow and the Moscow region, isolated local cases of TBE infection have been registered since 2011, which requires strengthening anti-epidemic measures. In the described clinical cases, a severe focal form of the disease was noted in children, in the first it ended with the formation of consequences in the form of symptomatic epilepsy, in the second – with a fatal outcome. Doctors of various profiles in endemic regions should be wary of TBE, and it is important to adhere to the correct tactics of managing patients with suspected infection. Key words: childhood morbidity, vaccination, tick-borne encephalitis, clinical forms, deaths, severe duration in children, Central Federal District

Оценка эффективности профилактических мероприятий, направленных на предупреждение заражения клещевым энцефалитом

Оценка эффективности профилактических мероприятий, направленных на предупреждение заражения клещевым энцефалитом

Geo-Spatial Characteristics of 567 Places of Tick-Borne Encephalitis Infection in Southern Germany, 2018-2020.

Tick-borne encephalitis (TBE) is a growing public health problem with increasing incidence and expanding risk areas. Improved prevention requires better understanding of the spatial distribution and ecological determinants of TBE transmission. However, a TBE risk map at sub-district level is still missing for Germany. We investigated the distribution and geo-spatial characteristics of 567 self-reported places of probable TBE infection (POI) from 359 cases notified in 2018–2020 in the study area of Bavaria and Baden-Wuerttemberg, compared to 41 confirmed TBE foci and 1701 random comparator places. We built an ecological niche model to interpolate TBE risk to the entire study area. POI were distributed heterogeneously at sub-district level, as predicted probabilities varied markedly across regions (range 0–93%). POI were spatially associated with abiotic, biotic, and anthropogenic geo-spatial characteristics, including summer precipitation, population density, and annual frost days. The model performed with 69% sensitivity and 63% specificity at an optimised probability threshold (0.28) and an area under the curve of 0.73. We observed high predictive probabilities in small-scale areas, consistent with the known circulation of the TBE virus in spatially restricted microfoci. Supported by further field work, our findings may help identify new TBE foci. Our fine-grained risk map could supplement targeted prevention in risk areas.

Incidence of Tick-Borne Encephalitis during the COVID-19 Pandemic in Selected European Countries.

Ixodes ricinus ticks are one of the most important vectors and reservoirs of infectious diseases in Europe, and tick-borne encephalitis (TBE) is one of the most dangerous human diseases transmitted by these vectors. The aim of the present study was to investigate the TBE incidence in some European countries during the COVID-19 pandemic. To this end, we analyzed the data published by the European Center for Disease Prevention and Control (ECDC) and Eurostat on the number of reported TBE and COVID-19 cases in 2020 and TBE cases in 2015–2019 (reference period). Significant differences in the TBE incidence were found between the analyzed countries. The highest TBE incidence was found in Lithuania (25.45/100,000 inhabitants). A high TBE incidence was also observed in Central European countries. In 12 of the 23 analyzed countries, there was significant increase in TBE incidence during the COVID-19 pandemic during 2020 compared to 2015–2019. There was no correlation between the incidence of COVID-19 and TBE and between the availability of medical personnel and TBE incidence in the studied countries. In conclusion, Central Europe and the Baltic countries are areas with a high risk of TBE infection. Despite the COVID-19 pandemic and imposed restrictions, the incidence of TBE is increasing in more than half of the analyzed countries.

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

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.

Epidemiology, diagnosis, and prevention of tick-borne encephalitis in Poland and selected European countries - a position statement of the Polish group of experts

Tick-borne encephalitis (TBE) is one of the most common viral neuroinfections in Poland. Detection of specific IgM and IgG anti- TBE antibodies in the serum or cerebrospinal fluid with enzyme-linked immunosorbent assay (ELISA) is a method of choice in TBE diagnostics. No effective antiviral treatment is available for TBE. Increased intracranial pressure, epileptic seizures, and other neurological symptoms in the course of TBE are managed with standard procedures. A routine use of corticosteroids is not recommended. Adults with TBE-related neurological sequelae should undergo physical mobilization and periodic neurological assessments. All patients ought to control their psychological condition and visit a physician in case of worrisome symptoms. Additionally, children need to undergo regular psychological and otolaryngologic consultations. Notably, TBE cases are reported across Poland; therefore, the entire country must be considered as a TBE risk region. The degree of endemicity can be variable in particular parts of the country. Immunization against TBE containing a European subtype of the virus is the most effective prophylactic method. In areas where the disease is highly endemic (according to the WHO definition of ≥5 cases/100 000 population/year), immunization needs to be offered to all ages. Vaccination is recommended in the communities living in areas of moderate TBE endemicity (1-5 cases/100 000/ year), in particular for individuals at high risk of a TBE infection as well as children and the elderly. Vaccination should also be offered to subjects living in areas where TBE occurrence is rare (<1 case/100 000/year) but who are at high risk of infection. A TBE vaccine is recommended to the following populations at high risk of TBE: a) individuals undertaking outdoor leisure activities, b) all professionals working outdoors, particularly in green areas, and c) individuals traveling to endemic areas, if activities during their visit may pose a risk of a tick bite. Post-exposure immunization is not recommended. Med Pr. 2021;72(2):193-210.

Современные возможности противовирусной терапии клещевого энцефалита у детей при остром и хроническом течении

Objective. To evaluate the efficacy of antiviral therapy and serotherapy for focal tick-borne encephalitis (TBE) in children with acute and chronic infection by assessing clinical and laboratory parameters, as well as MRI findings. Patients and methods. We followed-up 130 children aged 8 to 17 years with focal TBE affecting the central nervous system (CNS). Patients in groups 1 (n = 84) and 2 (n = 20) received therapy in the acute period of infection (on average 3.5 ± 1.3 days following disease onset). Patients in groups 3 (n = 15) and 4 (n = 11) received therapy for chronic TBE infection. Children from group 1 and 3 received antiviral therapy, including oral ribavirin, recombinant interferon-α2 (IFN-α2) (intramuscular injections or suppositories with antioxidants; Viferon®), and oral processed anti-IFN-γ antibodies (Anaferon for children). Children from groups 2 and 4 received serotherapy (anti-TBE immunoglobulin) and ribonuclease (intramuscular injections). Treatment duration depended on the disease phenotype; patients were followed-up for one year. Etiological diag-nostics included measurement of anti-TBE IgM and IgG and TBE antigen using enzyme-linked immunosorbent assays (ELISA), as well as detection of viral RNA in serum and cerebrospinal fluid (CSF) using polymerase chain reaction. All patients have undergone MRI of the brain and cervical spinal cord. Children were examined before treatment and then at several time-points during therapy. Results. In patients from group 1, the period of symptom increase was 4 days shorter than that in patients from group 2. In addition to that, their period of impaired consciousness and CSF pleocytosis was 5 days shorter than in group 2; they had more rapid viral clearance from CSF. Seventy patients from group 1 (83.3%) recovered without any deficit; none of them demonstrated progression of TBE infection. Six children from group 2 (30%) developed chronic TBE infection, whereas 11 patients (55%) had neurological deficit without progression as an outcome. The majority of patients from group 3 (86.7%) demonstrated improvement with one child who had complete regression of symptoms. In all participants from this group, virus replication was stopped. More than two-thirds of children from group 4 (72.7%) had aggravation of symptoms, persistent viral replication, and progression of atrophic CNS changes (according to MRI findings). Conclusion. Antiviral therapy (ribavirin, IFN-a2, and anti-IFN-γ antibodies) are most effective during the first 5 days of the disease; however, it was also effective in children with chronic TBE infection and ensured improvement with partial regression of symptoms. Anti-TBE immunoglobulin and ribonuclease were ineffective in children with focal TBE. Key words: viferon, children, tick-borne encephalitis, acute and chronic course, antiviral therapy, serotherapy

Ecological and epidemiological characteristics of tick-borne encephalitis in St. Petersburg

Here, we provide an analysis on 1996–2016 St. Petersburg tick-borne encephalitis (TBE) epidemiological and ecological data. In particular, two main TBE transmission vectors were observed in St. Petersburg: Ixodes persulcatus Ixodes ricinus. TBE tick contamination was 0.61% as shown by ELISA and polymerase chain reaction data. It is found that number of subjects seeking for medical aid due to tick bites rises, whereas TBE incidence declines. In particular, a mean 1996–2002 vs. 2010–2016 tick-bite incidence rate increased from 141.9 up to 288.9, respectively. Despite that the Leningrad region is a major area for TBE spread, however, a risk of exposure to tick bites as well as TBE infection exists even in the city of St. Petersburg. In connection with this, around 1,000 subjects undergo tick bites within the city limits. Moreover, whereas a 1996–2002 mean TBE incidence rate was 1.66, it decreased in 2010–2016 down to 1.17. A peak TBE incidence was documented in St. Petersburg Kurortny, Pushkinsky and Primorsky districts. In addition, males vs. females suffered from TBE at higher frequency in Russian Federation, with its peak incidence rate being reported in children under 14 that differs St. Petersburg from the most of other regions in the Russian Federation. A seasonal distribution of TBE cases in St. Petersburg does not differ from that one for the remainder of Russian regions, which displays a spring-summer seasonality lasting from April to September. Of note, 1996–2016 St. Petersburg TBE mortality was 1.37%. A coverage of TBE vaccinated population tends to rise but still remains at low level (0.25–0.58%). Lack of reported TBE cases in occupationally threatened human cohorts evidences about efficient preventive measures. Detection of TBE virus-specific serum antibodies in 5.0% apparently healthy and unvaccinated residents in St. Petersburg significantly complements the official TBE recording data and provides a more accurate understanding of its actual spread.

Acute tick-borne encephalitis during pregnancy – An alarming combination

We report on a pregnant patient who contracted tick-borne encephalitis (TBE) during her second trimester in an endemic region in Southern Germany. The patient presented with typical symptoms including fever and headache, and TBE infection was confirmed by positive blood and cerebrospinal fluid (CSF) testing. During acute infection there was no evidence of pregnancy complications, and the mother recovered well. We performed a clinical follow-up examination of both mother and child eight months after the diagnosis of TBE, which revealed no signs of sequelae.This case study presents rare evidence of TBE infection during pregnancy and may provide guidance for both physicians as well as mothers-to-be dealing with TBE.

Revealing new tick-borne encephalitis virus foci by screening antibodies in sheep milk

BackgroundTick distribution in Sweden has increased in recent years, with the prevalence of ticks predicted to spread towards the northern parts of the country, thus increasing the risk of tick-borne zoonoses in new regions. Tick-borne encephalitis (TBE) is the most significant viral tick-borne zoonotic disease in Europe. The disease is caused by TBE virus (TBEV) infection which often leads to severe encephalitis and myelitis in humans. TBEV is usually transmitted to humans via tick bites; however, the virus can also be excreted in the milk of goats, sheep and cattle and infection may then occur via consumption of unpasteurised dairy products. Virus prevalence in questing ticks is an unreliable indicator of TBE infection risk as viral RNA is rarely detected even in large sample sizes collected at TBE-endemic areas. Hence, there is a need for robust surveillance techniques to identify emerging TBEV risk areas at early stages.MethodsMilk and colostrum samples were collected from sheep and goats in Örebro County, Sweden. The milk samples were analysed for the presence of TBEV antibodies by ELISA and validated by western blot in which milk samples were used to detect over-expressed TBEV E-protein in crude cell extracts. Neutralising titers were determined by focus reduction neutralisation test (FRNT). The stability of TBEV in milk and colostrum was studied at different temperatures.ResultsIn this study we have developed a novel strategy to identify new TBEV foci. By monitoring TBEV antibodies in milk, we have identified three previously unknown foci in Örebro County which also overlap with areas of TBE infection reported during 2009–2018. In addition, our data indicates that keeping unpasteurised milk at 4 °C will preserve the infectivity of TBEV for several days.ConclusionsAltogether, we report a non-invasive surveillance technique for revealing risk areas for TBE in Sweden, by detecting TBEV antibodies in sheep milk. This approach is robust and reliable and can accordingly be used to map TBEV “hotspots”. TBEV infectivity in refrigerated milk was preserved, emphasising the importance of pasteurisation (i.e. 72 °C for 15 s) prior to consumption.

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.

Tick-borne encephalitis foci in northeast Italy revealed by combined virus detection in ticks, serosurvey on goats and human cases

ABSTRACT Tick-borne encephalitis (TBE) is a severe zoonotic neurological disease endemic in northeast Italy since 1992. In the Province of Trento, a sharp increase in TBE incidence has been recorded since 2012, despite the vaccination efforts. To assess current TBE infection hazard in this area, we applied an integrated approach combining the distribution of human cases, the seroprevalence of tick-borne encephalitis virus (TBEV) in sentinel hosts and the screening of questing ticks for TBEV. A total of 706 goat sera from 69 farms were screened for TBEV-specific antibodies resulting in 5 positive farms, while the location of human cases was provided by the local Public Health Agency. Tick sampling was concentrated in areas where TBEV circulation was suggested by either seroprevalence in goats or human cases, resulting in 2,410 Ixodes ricinus collected and analyzed by real-time RT–PCR. Four tick samples from 2 areas with record of human cases were positive to TBEV corresponding to a 0.17% prevalence in the region, while risk areas suggested by serology on goats were not confirmed by tick screening. Our results revealed an increase in TBEV prevalence in ticks and the emergence of new active TBE foci, compared to previous surveys, and demonstrated the importance of an integrated approach for TBE risk assessment. A phylogenetic analysis of the partial E gene confirmed that the European TBEV subtype is circulating in northeast Italy and suggested that the different Italian TBEV strains originated independently as a result of different introductions from neighbouring countries, presumably through migratory birds.

Knowledge, Attitudes, and Practices on Tick-Borne Human Diseases and Tick-Borne Encephalitis Vaccine among Farmers from North-Eastern Italy (2017)

ABSTRACTObjectives: Tick-borne diseases (T-BD) represent a potential health threat for outdoor workers in endemic areas, such as the Autonomous Province of Trento (APT). We conducted a questionnaire-based survey to assess T-BD knowledge, attitudes, and preventive practices among APT farmers, specifically focusing on the use of protective habits and the uptake of the tick-borne encephalitis (TBE) vaccine.Methods: A convenience sample of 106 farmers (all males, mean age 47.3 ± 13.6 years) attending pesticide training courses (12/2016–03/2017) completed the anonymous survey. Binary regression analysis, calculations of multivariate odds ratios (mOR) and 95% confidence intervals were used to assess knowledge, attitudes, and risk perceptions as predictors of preventive measures.Results: Though general understanding of T-BD was fairly low, the majority of the participants perceived TBE infection as a frequent (73.6%) and severe disease (61.3%). Overall, 43.3% of participants knew a TBE vaccine was available, and 24.5% had been vaccinated. Protective habits were reported by 53.8% of respondents, with self-checks for tick bites particularly low at 2.8% of participants. Better knowledge of T-BD and favorable attitudes toward vaccinations were associated with TBE immunization (mOR 4.708; 95%CI 1.273–17.409 and mOR 3.555; 95%CI 1.175–10.760, respectively), while previous history of tick bite and any interaction with T-BD significantly predicted adherence to protective measures (mOR 4.458; 95%CI 1.808–10.991, and mOR 9.433; 95%CI 1.127–78.973, respectively).Conclusions: Adherence to preventive measures (TBE vaccine) and protective habits was unsatisfactory in our sampled group, being a possible consequence of significant knowledge gaps. Public health communication on T-BD in farmers should, therefore, target understanding of health issues and appropriate preventive measures.

Assessing systemic and non-systemic transmission risk of tick-borne encephalitis virus in Hungary.

Estimating the tick-borne encephalitis (TBE) infection risk under substantial uncertainties of the vector abundance, environmental condition and human-tick interaction is important for evidence-informed public health intervention strategies. Estimating this risk is computationally challenging since the data we observe, i.e., the human incidence of TBE, is only the final outcome of the tick-host transmission and tick-human contact processes. The challenge also increases since the complex TBE virus (TBEV) transmission cycle involves the non-systemic route of transmission between co-feeding ticks. Here, we describe the hidden Markov transition process, using a novel TBEV transmission-human case reporting cascade model that couples the susceptible-infected compartmental model describing the TBEV transmission dynamics among ticks, animal hosts and humans, with the stochastic observation process of human TBE reporting given infection. By fitting human incidence data in Hungary to the transmission model, we estimate key parameters relevant to the tick-host interaction and tick-human transmission. We then use the parametrized cascade model to assess the transmission potential of TBEV in the enzootic cycle with respect to the climate change, and to evaluate the contribution of non-systemic transmission. We show that the TBEV transmission potential in the enzootic cycle has been increasing along with the increased temperature though the TBE human incidence has dropped since 1990s, emphasizing the importance of persistent public health interventions. By demonstrating that non-systemic transmission pathway is a significant factor in the transmission of TBEV in Hungary, we conclude that the risk of TBE infection will be highly underestimated if the non-systemic transmission route is neglected in the risk assessment.

Urgent natural foci infections transmitted by ticks in Saint-Petersburg

Purpose: to conduct a comparative analysis and to identify the epidemiological and clinical features of tick-borne encephalitis (TBE) and Lyme borreliosis as a mono- and coinfections in St. Petersburg. Materials and methods. 718 cases of TBE, 4353 cases of Lyme borreliosis and 127 combined diseases registered by the St. Petersburg epidemiological bureau in 2006-2017 were studied. Identification of combined diseases was carried out by a special software that allows to identify co-morbid diseases from the array of monoinfections. To identify clinical and epidemiological features, 144 cases of TBE, 286 Lyme borreliosis, and 43 cases of co-infection were studied. Age and sex characteristics, places of human contagion, infection rates of ticks, clinical forms of mono- and associated diseases, morbidity dynamics changes and patients’ IgM seropositivity were studied. Results. The long-term dynamics of TBE and Lyme borreliosis incidence had did not have significant upward or downward trends, it was characterized by synchronous fluctuations. The priority of the incidence of men over women is revealed. 61–69% cases of TBE and Lyme borreliosis occurred in Leningrad region, 19–30% – in the adjacent territories of Russia, 5,7–6,7% of cases were imported from other countries. High tick infection rates of TBE virus and Borrelia was revealed. Borrelia аnd virus of TBE and were detected in 81,6–87,5% of the examined ticks removed from patients with a later established diagnosis. Seasonal distribution of Lyme borreliosis was shifted by a month to the right in comparison with TBE. The clinical forms of both diseases did not differ in their structure from the country data, however after 2012 subclinical forms were more common in women. The proportion of non-erythematous forms of Lyme borreliosis in 2011–2015 compared with the 2006–2010 observation period increased almost 1,5-fold mainly forms, including those with co-infection. The IgM seropositivity rate in the dynamics of the disease testifies to the incomplete rehabilitation of patients. Conclusion. The clinical and epidemiological characteristics of TBE, Lyme borreliosis and combined infection in the North-West region of Russia, with the example of St. Petersburg, have certain distinctive features. The reasons for the revealed features need further study.

A Sensitive Nano Luciferase Immune Complex Assay System for Highly Sensitive and Specific Detection of Antibodies Against Tick-Borne Encephalitis Virus.

Tick-borne encephalitis virus (TBEV) can cause fever, headache, neurological disorders, and/or peripheral flaccid paralysis; therefore, it is a major threat to public health. A rapid, sensitive, and simple method for detecting anti-TBEV antibodies is needed urgently to determine infection and for vaccine evaluation. Here, a luciferase-based immunocomplex assay system (Luc-IC) was developed to detect TBEV antibodies. The system is based on a reporter Nano luciferase (NLuc) that is co-expressed as a fusion protein with viral envelope domain III (ED3) in COS7 cells. The cell supernatant was used directly to detect antigen without the need for a purification step. This simple procedure effectively improved the sensitivity of the assay. Sera from 50 patients with an acute tick-borne encephalitis infection were tested to determine the sensitivity of the NLuc-IC assay. Furthermore, 62 sera from individuals infected with Japanese encephalitis virus, West Nile virus, yellow fever virus, dengue virus, or Zika virus were also tested to determine specificity. The results demonstrated that the assay was 100% sensitive and 100% specific for TBEV antibodies. Thus, this very simple NLuc-IC assay is potentially useful for rapid and accurate diagnosis of TBEV infection in both humans and animals.

PIN105 - THE PUBLIC HEALTH IMPACT OF TICK-BORNE ENCEPHALITIS VACCINATION ON THE SLOVENIAN ADULT POPULATION

Despite Slovenia having one of the highest Tick-Borne Encephalitis (TBE) incidence rates in Europe, TBE vaccination coverage in Slovenia remains low in the general population. This study evaluates the potential public health impact of implementing an additional TBE universal mass vaccination (UMV) campaign for Slovenian adults of 45-50 years of age (YOA). A lifetime Markov cohort model was developed to reproduce the natural history of TBE infection in Europe. The study population of Slovenian adults, 45-50 YOA (total cohort size: 177,353), was followed using a 1-year cycle length, during which the probability of infection and moving to a specific health state was determined by age- and gender-specific incidence rates (corrected for underreporting) and specific state-to-state transition probabilities. It was assumed that the vaccination coverage was 50% and that the vaccinated population would be fully compliant with the conventional TBE vaccination schedule. Following the outcomes of recently published literature on the sustained immune response after TBE vaccination, an extension of the booster time-interval was explored from 3 or 5 years to 10 years irrespective of age. Implementing a UMV campaign for Slovenian adults of 45-50 YOA would reduce the total number of TBE cases by 761 cases (23.4%), of primary phase symptoms by 282 cases (23.4%) as well as of secondary phase symptoms by 19 cases (22.5%). Consequently, 332 to 498 days of hospitalization could be averted. An extension of the booster time-interval would prevent 52 cases (6.8%) less while the amount of secondary phase symptoms would increase by 1 case (5.2%). Nevertheless, the total amount of required booster doses would be reduced by 230,867 doses (39.5%). Implementing a TBE UMV campaign in the 45-50 YOA adult Slovenian population would result in a significant public health impact irrespective of an extended booster time-interval for the TBE-vaccine schedule.

Lethal Experimental Tick-Borne Encephalitis Infection: Influence of Two Strains with Similar Virulence on the Immune Response.

Tick-borne encephalitis virus (TBEV) is a tick-transmitted arbovirus that causes serious diseases in humans in Europe and Northern Asia. About 6000–10,000 cases are registered annually, and one-third of them lead to sequela with different degrees of severity. Two TBEV strains (Absettarov and EK-328) similar in virulence rate in laboratory mice were used to study pathogenesis and immune response upon lethal infection in mice. The strains differed in the dynamics of appearance of virus, IFNs and other cytokines in blood of mice, and ability to induce a cytokine storm in the terminal stages of disease and a non-sterile immunity. Moreover, the TBEV strains differed in characteristics of their interactions with DCs: level of reproduction in these cells, virus dose triggering IFN-α production, and impact on DCs' maturation. Infection of DCs with Absettarov strain led to IFN-α induction only at high multiplicity of infection (MOI), and an increased amount of the mature DCs with high adhesion activity and low-level of MHCII positive cells. While reproduction of the EK-328 strain in DCs was less efficient, a low dose of the virus induced IFN-α production and stimulated maturation of DCs with relatively low adhesive capacity, but with the high percentage of cells expressing MHCII molecules. Thus, the studied strains differed significantly in the impact on DCs' maturation and antigen presentation to CD4+ lymphocytes. Injection of low (103 PFU) and high (106 PFU) doses of both TBEV strains caused a lethal infection in mice. At the same time, the dose of the virus in the inoculum, regardless of the strain properties, affected the following virulence characteristics: the time of virus appearance in brain (day 4–5 vs. day 1 p.i.), time of IFN-α appearance in blood (10 h vs. 5 h p.i.), concentration of IFN-α in blood, and induction of IFN-α during infection of DCs. Therefore, virulent TBEV strains during lethal infection can interact differently with the host immune system, and the infectious dose has an impact on both: virus spread in the infected organism and immune response activation.