Tick-borne Encephalitis Virus Transmission Research Articles

Infection of wild-caught wood mice (Apodemus sylvaticus) and yellow-necked mice (A. flavicollis) with tick-borne encephalitis virus

The distribution of tick-borne encephalitis virus (TBEV) is expanding to Western European countries, including the Netherlands, but the contribution of different rodent species to the transmission of TBEV is poorly understood. We investigated whether two species of wild rodents native to the Netherlands, the wood mouse Apodemus sylvaticus and the yellow-necked mouse Apodemus flavicollis, differ in their relative susceptibility to experimental infection with TBEV. Wild-caught individuals were inoculated subcutaneously with the classical European subtype of TBEV (Neudoerfl) or with TBEV-NL, a genetically divergent TBEV strain from the Netherlands. Mice were euthanised and necropsied between 3 and 21 days post-inoculation. None of the mice showed clinical signs or died during the experimental period. Nevertheless, TBEV RNA was detected up to 21 days in the blood of both mouse species and TBEV was also isolated from the brain of some mice. Moreover, no differences in infection rates between virus strains and mouse species were found in blood, spleen, or liver samples. Our results suggest that the wood mouse and the yellow-necked mouse may equally contribute to the transmission cycle of TBEV in the Netherlands. Future experimental infection studies that include feeding ticks will help elucidate the relative importance of viraemic transmission in the epidemiology of TBEV.

Tick-Borne Encephalitis in a 6-Year-Old Patient: A Case Report.

Background: Tick-Borne Encephalitis virus (TBEV) is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family. TBEV transmission typically occurs through infected Ixodes tick bite or by consumption of unpasteurised milk from infected cattle. Case report: We report the clinical, neuroimaging, electroencephalogram (EEG), and laboratory (microbiological tests and spinal tap) data of a 6- year-old boy with Tick-borne encephalitis. Our patient presented with a biphasic course, initially with a myositis-like picture on his first admission to the emergency department, and after a few days with an encephalitic picture, resulting in a second hospitalization. EEG showed focal slow activity, while his brain magnetic resonance imaging (MRI) showed a signal abnormality, which completely resolved on repeat MRI after 3 months. Conclusion: To our knowledge, this is the youngest patient presenting with myositis in the first phase of Tick-borne encephalitis (TBE). In the presence of a biphasic clinical course, with previous myositis, aspecific MRI changes in the thalamic and midbrain regions and an EEG documenting slowed bioelectrical activity should prompt suspicion of TBEV infection.

Breast Milk: A Potential Route of Tick-Borne Encephalitis Virus Transmission from Mother to Infant.

Tick-borne encephalitis virus (TBEV) is a global public health concern, and understanding its transmission routes is crucial for effective prevention and control. While tick bites are the primary mode of TBEV transmission, emerging evidence suggests the potential for TBEV transmission through breast milk from infected mothers to their infants. This review article provides an overview of the current knowledge regarding TBEV transmission through breast milk and its clinical implications. It explores the presence and persistence of TBEV in breast milk, potential mechanisms of transmission, and the role of immune factors in facilitating or inhibiting viral transmission. The clinical outcomes and complications in infants infected with TBEV through breast milk are discussed, along with the epidemiological patterns and geographical considerations of this transmission mode. Preventive and management strategies are also addressed, including public health measures, risk assessment, and potential interventions. Future research directions are highlighted, emphasizing the need for further epidemiological studies, investigations into viral load dynamics, immune responses, and the development of preventive measures targeting TBEV transmission through breast milk. By expanding our knowledge in these areas, we can improve strategies to reduce the risk of TBEV transmission from mothers to infants and protect vulnerable populations.

Seroprevalence of tick-borne encephalitis virus in wild and domestic animals in northern Germany

Tick-borne encephalitis virus (TBEV) is a tick-transmitted flavivirus, which can infect humans and animals, sometimes even with a fatal outcome. Since many decades, TBEV is endemic in southern Germany, while only sporadic occurrence has been noted in northern parts of the country so far. Nevertheless, autochthonous human clinical cases are increasing in the federal state of Lower Saxony in north-western Germany, and several natural foci of TBEV transmission have recently been detected in this federal state. In order to shed more light on the current distribution of TBEV in Lower Saxony, the present study examined blood samples from wild and domestic animals for antibodies against TBEV. Overall, samples from 4,085 animals were tested by ELISA, including wild boar (N = 1,208), roe deer (N = 149), red deer (N = 61), fallow deer (N = 18), red foxes (N = 9), nutria (N = 9), raccoon dogs (N = 3), raccoons (N = 3), badgers (N = 1), European pine martens (N = 1), horses (N = 574), sheep (N = 266), goats (N = 67), dogs (N = 1,317) and cats (N = 399). Samples with an ELISA result of ≥60 Vienna units (VIEU)/ml were subjected to confirmatory serum neutralization tests (SNT). In total, 343 of 4,085 (8.4%) animals tested positive for anti-TBEV-IgG by ELISA, of which 60 samples were confirmed by SNT. Samples of 89 animals showed a cytotoxic effect in the SNT and were excluded from seroprevalence calculation, resulting in an overall seroprevalence of 1.5% (60/3,996). Seroprevalence was higher among wild animals (wild boar: 2.9% [34/1,190], roe deer: 2.7% [4/149], red deer: 1.7% [1/60], fallow deer: 5.6% [1/18]) than among domestic animals (dogs: 1.1% [15/1,317], horses: 0.8% [4/505], sheep: 0.4% [1/266]). No anti-TBEV-antibodies were detected in the other wild animal species as well as goats and cats. A notable clustering of positive samples was observed in districts where TBEV transmission foci have been described. Further clusters in other districts suggest the existence of so far undetected transmission foci, underlining the fact that both wild and domestic animals are useful sentinels for monitoring the spread of TBEV.

The thick-borne encephalitis caused by alimentary transmission - case series report.

Tick-borne encephalitis (TBE) is a central nervous system zoonotic disease transmitted by ticks. Tick-borne encephalitis virus (TBEV) is one of the main causes of lymphocytic meningitis in the areas of its endemic occurrence. A mode of transmission of TBEV which is rarely observed in clinical practice is an alimentary transmission through consumption of unpasteurised dairy products from infected animals. The following article contains detailed description of the clinical course of TBE among five family members, for whom the occurrence of TBE was temporarily associated with the consumption of unpasteurised goat's milk from the same source. The epidemiological outbreak presented in this article is the fifth ever described case of the milk-borne TBE in Poland. More so, the clinical course of the disease has shown differences from the typical course characterised so far in the literature. Clinical cases of TBE described in this study were similar to infections caused by tick bites in humans. The following article discusses available methods of preventing TBE, with emphasis on alimentary transmission of TBEV, since possibility of serious detrimental long-term neurological complications resulting from TBE was stressed in prior literature.

Prevalence of tick-borne encephalitis virus in questing Ixodes ricinus nymphs in southern Scandinavia and the possible influence of meteorological factors.

Ixodes ricinus ticks are Scandinavia's main vector for tick-borne encephalitis virus (TBEV), which infects many people annually. The aims of the present study were (i) to obtain information on the TBEV prevalence in host-seeking I. ricinus collected within the Øresund-Kattegat-Skagerrak (ØKS) region, which lies in southern Norway, southern Sweden and Denmark; (ii) to analyse whether there are potential spatial patterns in the TBEV prevalence; and (iii) to understand the relationship between TBEV prevalence and meteorological factors in southern Scandinavia. Tick nymphs were collected in 2016, in southern Scandinavia, and screened for TBEV, using pools of 10 nymphs, with RT real-time PCR, and positive samples were confirmed with pyrosequencing. Spatial autocorrelation and cluster analysis was performed with Global Moran's I and SatScan to test for spatial patterns and potential local clusters of the TBEV pool prevalence at each of the 50 sites. A climatic analysis was made to correlate parameters such as minimum, mean and maximum temperature, relative humidity and saturation deficit with TBEV pool prevalence. The climatic data were acquired from the nearest meteorological stations for 2015 and 2016. This study confirms the presence of TBEV in 12 out of 30 locations in Denmark, where six were from Jutland, three from Zealand and two from Bornholm and Falster counties. In total, five out of nine sites were positive from southern Sweden. TBEV prevalence of 0.7%, 0.5% and 0.5%, in nymphs, was found at three sites along the Oslofjord (two sites) and northern Skåne region (one site), indicating a potential concern for public health. We report an overall estimated TBEV prevalence of 0.1% in questing I. ricinus nymphs in southern Scandinavia with a region-specific prevalence of 0.1% in Denmark, 0.2% in southern Sweden and 0.1% in southeastern Norway. No evidence of a spatial pattern or local clusters was found in the study region. We found a strong correlation between TBEV prevalence in ticks and relative humidity in Sweden and Norway, which might suggest that humidity has a role in maintaining TBEV prevalence in ticks. TBEV is an emerging tick-borne pathogen in southern Scandinavia, and we recommend further studies to understand the TBEV transmission potential with changing climate in Scandinavia.

Hybrids of Ixodes ricinus and Ixodes persulcatus ticks effectively acquire and transmit tick-borne encephalitis virus.

Ixodes rici nus and Ixodes persulcatus ticks are the main vectors of tick-borne encephalitis virus (TBEV), which has three main subtypes connected with certain tick species: the European subtype, associated with I. ricinus, and the Siberian and Far-Eastern subtypes, associated with I. persulcatus. Distribution ranges of these species overlap and form large sympatric areas in the East European Plain and Baltic countries. It has previously been shown that crossing of I. ricinus and I. persulcatus is possible, with the appearance of sterile hybrids. Hybridization of ticks can affect not only the spread of ticks but also the properties of natural foci of arbovirus infections, in particular TBEV. In the present study, we analyzed the effectiveness of virus transmission from infected mice to larvae and nymphs and trans-stadial transmission (from larvae to nymph and adult) in I. ricinus, I. persulcatus, and hybrids. For this purpose, we bred a hybrid generation from the crossing of I. persulcatus females and I. ricinus males, and we used the Siberian and European subtypes of TBEV. We showed that after feeding on infected mice, virus prevalence in engorged ticks decreased over time, and after molting, the opposite was true. In hybrids we observed the highest acquisition effectiveness and RNA copy numbers during Siberian TBEV subtype transmission. The efficiency of trans-stadial transmission of both TBEV subtypes was similar in hybrids and parental species. After the second trans-stadial TBEV transmission, a significant increase in ticks' infection rates was observed only in specific subtype-tick combination. Our data demonstrate the possible features of TBEV circulation in the I. ricinus and I. persulcatus sympatry area.

Tick-Borne Encephalitis: An Update for the Special Operations Forces Provider.

Tick-borne encephalitis (TBE) is a severe disease caused by the tick-borne encephalitis virus (TBEV). TBEV is endemic throughout Eurasia and can cause persistent neurologic deficits and death. Special Operations Forces (SOF) participating in field exercises or operations in TBE-endemic countries are at significantly increased risk of infection. Unlike Lyme disease and other tick-borne illnesses, transmission of TBEV can be immediate, and early tick removal does not reduce the risk of infection. While there are no virus-specific treatments available, the US Food and Drug Administration (FDA) recently approved a TBE vaccine that has yet to be incorporated into formal Department of Defense (DoD) recommendations. SOF medical providers should be aware of this disease entity and consider the TBE vaccine when planning exercises and operations in areas of responsibility (AORs) with TBE-endemic countries. This review serves as a refresher and update on the epidemiology, transmission, and management of TBE for the SOF provider.

Functional characterization and immunogenicity of a novel vaccine candidate against tick-borne encephalitis virus based on Leishmania-derived virus-like particles

Tick-borne encephalitis virus (TBEV) is a major cause of neurological infections in many regions of central, eastern and northern Europe and northern Asia. In approximately 15% of cases, TBEV infections lead to the development of severe encephalitis or meningitis. The main route of TBEV transmission is tick bites; however, ingestion of dairy products from infected animals (goats, cattle and sheep) is also a frequent cause of the disease. Therefore, vaccination of livestock in virus endemic regions could also contribute to the decrease in TBEV infection among humans. Although few vaccines against TBEV based on inactivated viruses are available for humans, due to high costs, vaccination is not mandatory in most of the affected countries. Moreover, there is still no vaccine for veterinary use. Here, we present a characterization and immunogenicity study of a new potential TBEV vaccine based on virus-like particles (VLPs) produced in Leishmania tarentolae cells. VLPs, which mimic native viral particles but do not contain genetic material, show good immunogenic potential. For the first time, we showed that the protozoan L. tarentolae expression system can be successfully used for the production of TBEV virus-like particles with highly efficient production. We confirmed that TBEV recombinant structural proteins (prM/M and E) from VLPs are highly recognized by neutralizing antibodies in in vitro analyses. Therefore, VLPs in combination with AddaVax adjuvant were used in immunization studies in a mouse model. VLPs proved to be highly immunogenic and induced the production of high levels of neutralizing antibodies. In a challenge experiment, immunization with VLPs provided full protection from lethal TBE in mice. Thus, we suggest that Leishmania-derived VLPs may be a good candidate for a safe alternative human vaccine with high efficiency of production. Moreover, this potential vaccine candidate may constitute a low-cost candidate for veterinary use.

Method for tick-borne encephalitis virus detection in raw milk products

The transmission of tick-borne encephalitis virus (TBEV) through food is rare, but can occur through the consumption of raw milk products from animals infected by tick bites. In 2020, France faced a TBEV outbreak linked to the consumption of unpasteurized goat cheese. The aim of this study was to develop and characterize a molecular method for the detection of TBEV in raw milk products based on the recent international standard PR ISO/DIS 16140-4. The TBEV recovery rates varied with the inoculation level and settings. The LOD50 and LOD95 of TBEV were 6.40 × 103 genome copies per g or per mL and 2.84 × 104 genome copies per g or per mL, respectively. The percentages of RT-qPCR inhibitions were lower than 75% and the murine norovirus (MNV-1), used as process control, was detected in all samples with a recovery rate higher than 1%, as recommended in ISO 15216. We conclude that the described method is appropriate to detect TBEV in raw milk products for routine diagnosis, and to assess potential health risks.

Long-term presence of tick-borne encephalitis virus in experimentally infected bank voles (Myodes glareolus)

Tick-borne encephalitis virus (TBEV) is a vector-borne pathogen that can cause serious neurological symptoms in humans. Across large parts of Eurasia TBEV is found in three traditional subtypes: the European, the Siberian and the Far-eastern subtype. Small mammalian animals play an important role in the transmission cycle as they enable the spread of TBEV among the vector tick population. To assess the impact of TBEV infection on its natural hosts, outbred bank voles (Myodes glareolus) were inoculated with one out of four European TBEV strains. Three of these TBEV strains were recently isolated in Germany. The forth one was the TBEV reference strain Neudörfl. Sampling points at 7, 14, 28, and 56 days post inoculation allowed the characterization of the course of infection. At each time point, six animals per strain were euthanized and eleven organ samples (brain, spine, lung, heart, small and large intestine, liver, spleen, kidney, bladder, sexual organ) as well as whole blood and serum samples were collected. The majority of bank voles (92/96) remained clinically unaffected after the inoculation with TBEV, but still developed a systemic infection during the first week, which transitioned to a viraemia and an infestation of the brain in some animals for the remainder of the first month. Viral RNA was found in whole blood samples of several animals (50/96), but only in a small fraction of the corresponding serum samples (4/50). From the whole blood, virus was successfully reisolated in cell culture until 14 days after inoculation. Less than five percent of all inoculated bank voles (4/96) displayed signs of distress in combination with a rapid weight loss and had to be euthanized prematurely. Overall, the recently isolated TBEV strains showed marked differences, such as a more frequent development of long-term viraemia and a higher detection rate of viral RNA in various organs, in comparison to the reference strain Neudörfl.Overall, our data suggest that the bank vole is a potential amplifying host in the TBEV transmission cycle and appears to be highly adapted to circulating TBEV strains.

Contact-dependent transmission of Langat and tick-borne encephalitis virus in type I interferon receptor-1 deficient mice.

Tick-borne encephalitis virus (TBEV) is primarily transmitted to humans through tick bites or oral consumption of accordingly contaminated unpasteurized milk or milk products. The detection of TBEV RNA in various body fluids in immunosuppressed human patients is documented. However, the risk of direct contact exposure remains unclear. Interferon-alpha receptor-1 deficient (Ifnar1-/- ) mice, which are lacking the interferon-α/β responses, develop neurologic manifestations after infection with TBEV and Langat virus (LGTV). We showed that subcutaneous, intranasal, and peroral infection of LGTV lead to disease, whereas mice with intragastric application of LGTV showed no disease signs. With LGTV infected mice exhibit seroconversion and significant viral RNA levels was detected in saliva, eye smear, feces and urine. As a result, TBEV and LGTV are transmitted between mice from infected to naïve co-caged sentinel animals. Although intranasal inoculation of LGTV is entirely sufficient to establish the disease in mice, the virus is not transmitted by aerosols. These pooled results from animal models highlight the risks of exposure to TBEV contaminants and the possibility for close contact transmission of TBEV in interferon-alpha receptor-1 deficient laboratory mice.Importance Tick-borne encephalitis is a severe disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). Every year between 10,000-12,000 people become infected with this flavivirus. The TBEV is usually transmitted to humans via the bite of a tick, but infections due to consumption of infectious milk products are increasingly being reported. Since there is no therapy for an TBEV infection and mechanisms of virus persistence in reservoir animals are unclear, it is important to highlight the risk of exposure to TBEV contaminants and know possible routes of transmission of this virus. The significance of our research is in identifying other infection routes of TBEV and LGTV, and the possibility of close contact transmission.

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

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.

Operational TBE incidence forecasts for Austria, Germany, and Switzerland 2019–2021

In spring 2019, forecasts of the incidence of tick-borne encephalitis (TBE) for the next 2 years, i.e. 2019 and 2020, were made for the first time. For this purpose, negative binomial regression models with 4–5 predictors were fitted to the time series of annual human TBE incidences from Austria, Germany, and Switzerland. The most important predictor for TBE incidences is the fructification index of the European beech (Fagus sylvatica) 2 years prior as a proxi for the intensity of the TBE virus transmission cycle. These forecasts were repeated in spring 2020 after the updated predictors and the confirmed TBE cases for 2019 became available. Forecasting TBE incidences for 2020 and 2021 results in 156 ± 19 and 131 ± 23 TBE cases for Austria, 663 ± 95 and 543 ± 112 TBE cases for Germany as well as 472 ± 56 and 350 ± 62 TBE cases for Switzerland. The newly implemented operational TBE forecasts will be verified every year with confirmed TBE cases. An initial verification for 2019 demonstrates the high reliability of the forecasts.

Tick-borne encephalitis incidence forecasts for Austria, Germany, and Switzerland

The forecast of human tick-borne encephalitis (TBE) incidence for the next years has been on the research agenda of epidemiologists since the discovery of this tick-borne zoonosis. Based on models to explain the trend as well as the low- and high-frequency oscillations in the Austrian TBE incidence series, TBE forecasts for Austria, Germany and Switzerland are presented here. For this purpose, generalized linear models (GLMs) of type negative binomial regression were calibrated with the TBE incidences of the period 1991–2018 to forecast the TBE incidences 2019 and 2020. The GLMs require only 4–5 predictors, 2 of which are large-scale synchronized over Central Europe and used for all 3 countries. Predictors used include the demographic parameters total population and net migration rate, the Scandinavian index which describes the large-scale atmospheric circulation patterns, the fructification index of the European beech (Fagus sylvatica) 2 years prior as a proxy for the intensity of the TBE virus transmission cycle, and the national TBE vaccination coverage. Since an official time series of TBE vaccination coverage is only available for Austria, the missing TBE vaccination coverages of Germany and Switzerland were reconstructed and presented as the first results. Model verification results in explained variances of 76% for Austria, 84% for Germany, and 89% for Switzerland. Thus, the best model fit was determined for the Swiss GLM which is able to predict the TBE incidence with a root-mean-square error of RMSE = 25 cases (19% of the mean TBE incidence 1991–2018 or 7% of the TBE incidence of 2018). Forecasting TBE incidences for 2019 and 2020 results in 92 ± 12 and 142 ± 26 TBE cases for Austria, 417 ± 71 and 670 ± 168 TBE cases for Germany as well as 235 ± 30 and 465 ± 91 TBE cases for Switzerland.

The potential impact of climate change on the transmission risk of tick-borne encephalitis in Hungary

BackgroundImpact of climate change on tick-borne encephalitis (TBE) prevalence in the tick-host enzootic cycle in a given region depends on how the region-specific climate change patterns influence tick population development processes and tick-borne encephalitis virus (TBEV) transmission dynamics involving both systemic and co-feeding transmission routes. Predicting the transmission risk of TBEV in the enzootic cycle with projected climate conditions is essential for planning public health interventions including vaccination programs to mitigate the TBE incidence in the inhabitants and travelers. We have previously developed and validated a mathematical model for retroactive analysis of weather fluctuation on TBE prevalence in Hungary, and we aim to show in this research that this model provides an effective tool for projecting TBEV transmission risk in the enzootic cycle.MethodsUsing the established model of TBEV transmission and the climate predictions of the Vas county in western Hungary in 2021-2050 and 2071-2100, we quantify the risk of TBEV transmission using a series of summative indices - the basic reproduction number, the duration of infestation, the stage-specific tick densities, and the accumulated (tick) infections due to co-feeding transmission. We also measure the significance of co-feeding transmission by observing the cumulative number of new transmissions through the non-systemic transmission route.ResultsThe transmission potential and the risk in the study site are expected to increase along with the increase of the temperature in 2021-2050 and 2071-2100. This increase will be facilitated by the expected extension of the tick questing season and the increase of the numbers of susceptible ticks (larval and nymphal) and the number of infected nymphal ticks co-feeding on the same hosts, leading to compounded increase of infections through the non-systemic transmission.ConclusionsThe developed mathematical model provides an effective tool for predicting TBE prevalence in the tick-host enzootic cycle, by integrating climate projection with emerging knowledge about the region-specific tick ecological and pathogen enzootic processes (through model parametrization fitting to historical data). Model projects increasing co-feeding transmission and prevalence of TBEV in a recognized TBE endemic region, so human risk of TBEV infection is likely increasing unless public health interventions are enhanced.

Incorporating tick feeding behaviour into [formula omitted] for tick-borne pathogens

Tick-borne pathogens pose a considerable disease burden in Europe and North America, where increasing numbers of human cases and the emergence of new tick-borne pathogens has renewed interest in resolving the mechanisms underpinning their geographical distribution and abundance. For Borrelia burgdorferi and tick-borne encephalitis (TBE) virus, transmission of infection from one generation of ticks to another occurs when older nymphal ticks infect younger larval ticks feeding on the same host, either indirectly via systemic infection of the vertebrate host or directly when feeding in close proximity. Here, expressions for the basic reproduction number, R0, and the related tick type-reproduction number, T, are derived that account for the observation that larval and nymphal ticks tend to aggregate on the same minority of hosts, a tick feeding behaviour known as co-aggregation. The pattern of tick blood meals is represented as a directed, acyclic, bipartite contact network, with individual vertebrate hosts having in-degree, kin, and out-degree, kout, that respectively represent cumulative counts of nymphal and larval ticks fed over the lifetime of the host. The in- and out-degree are not independent when co-aggregation occurs such that T∝〈kinkout〉〈kin〉,where 〈.〉 indicates expected value. When systemic infection in the vertebrate host is the dominant transmission route R02=T, whereas when direct transmission between ticks co-feeding on the same host is dominant then R0=T and the effect of co-aggregation on R0 is more pronounced. Simulations of B. burgdorferi and TBE virus transmission on theoretical tick-mouse contact networks revealed that aggregation and co-aggregation have a synergistic effect on R0 and T, that co-aggregation always increases R0 and T, and that aggregation only increases R0 and T when larvae and nymphs also co-aggregate. Co-aggregation has the greatest absolute effect on R0 and T when the mean larval burden of hosts is high, and the largest relative effect on R0 for pathogens sustained by co-feeding transmission, e.g. TBE virus in Europe, compared with those predominantly spread by systemic infection, e.g. B. burgdorferi. For both pathogens, though, co-aggregation increases the mean number of ticks infected per infectious tick, T, and so too the likelihood of pathogen persistence.

Exploring the Reservoir Hosts of Tick-Borne Encephalitis Virus.

Tick-borne encephalitis virus (TBEV) is an important arbovirus, which is found across large parts of Eurasia and is considered to be a major health risk for humans. Like any other arbovirus, TBEV relies on complex interactions between vectors, reservoir hosts, and the environment for successful virus circulation. Hard ticks are the vectors for TBEV, transmitting the virus to a variety of animals. The importance of these animals in the lifecycle of TBEV is still up for debate. Large woodland animals seem to have a positive influence on virus circulation by providing a food source for adult ticks; birds are suspected to play a role in virus distribution. Bank voles and yellow-necked mice are often referred to as classical virus reservoirs, but this statement lacks strong evidence supporting their highlighted role. Other small mammals (e.g., insectivores) may also play a crucial role in virus transmission, not to mention the absence of any suspected reservoir host for non-European endemic regions. Theories highlighting the importance of the co-feeding transmission route go as far as naming ticks themselves as the true reservoir for TBEV, and mammalian hosts as a mere bridge for transmission. A deeper insight into the virus reservoir could lead to a better understanding of the development of endemic regions. The spatial distribution of TBEV is constricted to certain areas, forming natural foci that can be restricted to sizes of merely 500 square meters. The limiting factors for their occurrence are largely unknown, but a possible influence of reservoir hosts on the distribution pattern of TBE is discussed. This review aims to give an overview of the multiple factors influencing the TBEV transmission cycle, focusing on the role of virus reservoirs, and highlights the questions that are waiting to be further explored.

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.

Emergence of tick-borne encephalitis (TBE) in the Netherlands

Recently, tick-borne encephalitis virus (TBEV) was detected in the Netherlands for the first time, in ticks collected in 2015 in the National Park Sallandse heuvelrug in response to the detection of anti-TBEV antibodies in roe deer. Hereafter, two human cases of autochthonous TBE have been reported, occurring in 2016. One case was geographically linked to the area of the previously reported ticks, which harbored a genetically divergent TBEV-Eu strain variant (TBEV-NL). So far these are the few reported events that point to endemic transmission of TBEV in the Netherlands and the true prevalence of TBEV and TBE disease in the Netherlands and its impact on the human population remains to be determined. We describe the third human case, identified in 2017, which geographically clusters with the aforementioned case and TBEV-positive ticks. We also describe the identification of another TBEV-NL-positive tick in the Netherlands, collected 2 years after the initial find in that same region (in 2017). These observations support the concept of continued circulation of TBEV-NL and the presence of a possible TBEV hot spot in the Sallandse Heuvelrug region.