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Histopathological analyses of brain tissue at autopsy. Hematoxylin and eosin-stained section. (A) Parenchymal infiltrates in a widespread distribution, multiple foci of lymphocytic meningitis. Magnification 100×. Scale bar corresponds to 200 µm. (B) Infiltrates in leptomeninges. Magnification 400×. Scale bar corresponds to 50 µm.
Source publication
Tick-borne encephalitis is a viral disease affecting the central nervous system. It is endemic in Switzerland with 200–250 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 ou...
Citations
... Among TBE cases, we further found that the odds of a meningitis diagnosis were substantially increased (compared to having no or questionable neurological symptoms) among unvaccinated individuals, consistent with the protective role of vaccination. While controversial, it has been speculated that TBE vaccination breakthrough infections might be associated with a more severe disease course compared with unvaccinated individuals [13,15,[37][38][39]. Our findings, however, do not support this. ...
Background
Tick-borne encephalitis (TBE) is a severe, vaccine-preventable viral infection of the central nervous system. Symptoms are generally milder in children and adolescents than in adults, though severe disease does occur. A better understanding of the disease burden and duration of vaccine-mediated protection is important for vaccination recommendations.
Aim
To estimate TBE vaccination coverage, disease severity and vaccine effectiveness (VE) among individuals aged 0–17 years in Switzerland.
Methods
Vaccination coverage between 2005 and 2022 was estimated using the Swiss National Vaccination Coverage Survey (SNVCS), a nationwide, repeated cross-sectional study assessing vaccine uptake. Incidence and severity of TBE between 2005 and 2022 were determined using data from the Swiss disease surveillance system and VE was calculated using a case–control analysis, matching TBE cases with SNVCS controls.
Results
Over the study period, vaccination coverage increased substantially, from 4.8% (95% confidence interval (CI): 4.1–5.5%) to 50.1% (95% CI: 48.3–52.0%). Reported clinical symptoms in TBE cases were similar irrespective of age. Neurological involvement was less likely in incompletely (1–2 doses) and completely (≥ 3 doses) vaccinated cases compared with unvaccinated ones. For incomplete vaccination, VE was 66.2% (95% CI: 42.3–80.2), whereas VE for complete vaccination was 90.8% (95% CI: 87.7–96.4). Vaccine effectiveness remained high, 83.9% (95% CI: 69.0–91.7) up to 10 years since last vaccination.
Conclusions
Even children younger than 5 years can experience severe TBE. Incomplete and complete vaccination protect against neurological manifestations of the disease. Complete vaccination offers durable protection up to 10 years against TBE.
... In ad di tion to the high prev a lence of TBE, di verse clini cal man i fes ta tions are also of great con cern, as the dis ease may vary from asymp tom atic in fec tion to a se vere meningoencephalomyelitic form [5,7]. Fur ther more, TBE may be a le thal dis ease [8][9][10]. Ret ro spec tive fol low-up stud ies in di cate the mor tal ity rate of tick-borne en ceph a litis to be 0-1.4% [2]. ...
Background. In Lithuania, the incidence rate of tick-borne encephalitis (TBE) increases and remains the highest in the whole Europe. Diverse clinical manifestations cause difficulties in diagnosing and treating this infectious disease. The aim of the study was to analyze clinical manifestations of the TBE and to indicate predictive variables for unfavorable outcome. Methods. A retrospective study of case histories of patients diagnosed with TBE and treated at the Vilnius University Hospital Santaros Klinikos in the years 2019-2021. Demographic variables, symptoms and clinical form of the disease, laboratory values, and aspects of treatment were recorded. Results. Six hundred and seven case histories were analyzed. Of these, 588 case histories were included in the final analysis. Men made up 56.97% of the population studied. The median age of the patients was 54 years (18-86). The median length of hospitalization was 9 days (1-50). Seventeen (2.89%) patients were immunized against TBE, the others were not immunized (401, 68.20%) or their immunization status was unknown (170, 28.91%). The most common symptoms were headache (509, 86.56%) followed by febrile fever (403, 68.54%), fatigue (400, 68.03%), and dizziness (394, 67.01%). The most prevalent clinical form of TBE cases was meningoencephalitis (387, 76.18%) followed by meningitis (88, 17.32%), meningoencephalomyelitis (29, 5.71%), and encephalitis (4, 0.79%). Patients with the meningoencephalomyelitic form of TBE less often had headache on admission, more often had diabetes, and had fewer lymphocytes in the CSF (all p<0.05). Six patients (1.02%) died. The latter patients were significantly older (71 vs. 53 years, p=0.003), had higher protein concentration and cytosis in the CSF (1.04 vs. 0.70 g/L, p=0.006 and 422 vs. 84 cells per milliliter, p=0.003, respectively), whereas the percentage of lymphocytes in the CSF was lower (62% vs. 81%, p<0.001). Univariate analysis showed that older age, absence of headache and fatigue, higher cytosis and percentage of neutrophils in the CSF may be prognostic variables for the lethal outcome of the disease. Multivariate analysis showed that the absence of fatigue and higher pleocytosis were significant predictors of unfavorable outcome. Conclusions. Clinical forms of TBE differ based on symptoms and laboratory values. Symptoms and laboratory results may prognose the outcome of the disease.
... In contrast, survival following lethal TBEV infection in SCID and CD8-knockout mice was increased compared to wildtype or mice with adoptively transferred CD8+ T cells, demonstrating that CD8+ T cells can also contribute to lethal infection (44). Similarly, CD8+ T cell infiltrates are commonly found in the post-mortem brains of fatal TBE cases (70)(71)(72), and a separate study found that, in severely infected patients, nearly all virus-specific CD8+ T cells expressed a4 and b1 integrins (VLA-4), which are important in lymphocyte homing and the ability of cells to cross the blood-brain barrier (69). However, breakdown of the BBB during infection in mice was observed in both wildtype and CD8-knockout animals, indicating that CD8+ T cells are not responsible for BBB permeability during disease (46). ...
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.
... Several fatal cases of TBE have been described in immunocompromised patients ( Table 2 in supplementary file). Factors, that decreased patients immunity, were among other medications for autoimmunological disorders (Knight et al., al.,2017;Steininger et al., 2017;Sendi et al., 2017;De Bruijn et al., 2015;Zajkowska et al., 2011). TBEV can be a potential threat to organ transplant recipients. ...
... The disease can be effectively prevented by vaccination. However, a standard TBEV vaccine schedule may not provide enough cellular immunogenicity in immunosuppressed patients, and TBE can occur even with a full course of vaccination (Sendi et al., 2017). In a study conducted by Hertzell et al. (2016), post-vaccine levels of neutralizing antibodies against TBE virus were evaluated in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors and/or methotrexate when compared with healthy matched controls. ...
Tick-borne encephalitis (TBE) is an infectious illness of the central nervous system caused by the TBE virus, which is commonly transmitted through a tick-bite. TBE is endemic in Europe and mid-Asia. In this study, we report a case of a 36-year-old woman, living in Northeastern Poland, with a history of double corneal transplantation and post-transplant immunosuppressive therapy who was admitted to hospital because of progressive weakness, acute headache, nausea, vertigo, vomiting, and fever. The patient was diagnosed with TBE. However, the diagnosis was challenging as the initial serological tests for antibodies against the TBE virus were negative. We want to raise the awareness among the clinicians that the course of TBE is often unpredictable and that it tends to be more severe in immunocompromised individuals. Delayed production of antibodies against TBE virus, which might inhibit the diagnosis of the disease, is observed in some immunocompromised patients.
... 14,40,147,148 Studies of the immunogenicity and safety of TBE vaccines show high and long-lasting immunogenicity, with acceptable rates of adverse events following vaccination. 107,149-152 TBE breakthrough after vaccination has rarely been reported, 14,153,154 in only 1%-6% of TBE cases with a vaccination history vaccine breakthrough are found. 20 ...
European and Asian countries. It is an emerging public health problem, with steadily increasing case numbers over recent decades. Tick-borne encephalitis virus affects between 10,000 and 15,000 patients annually. Infection occurs through the bite of an infected tick and, much less commonly, through infected milk consumption or aerosols. The TBEV genome comprises a positive-sense single-stranded RNA molecule of ∼11 kilobases. The open reading frame is > 10,000 bases long, flanked by untranslated regions (UTR), and encodes a polyprotein that is co- and post-transcriptionally processed into three structural and seven non-structural proteins. Tick-borne encephalitis virus infection results in encephalitis, often with a characteristic biphasic disease course. After a short incubation time, the viraemic phase is characterised by non-specific influenza-like symptoms. After an asymptomatic period of 2–7 days, more than half of patients show progression to a neurological phase, usually characterised by central and, rarely, peripheral nervous system symptoms. Mortality is low—around 1% of confirmed cases, depending on the viral subtype. After acute tick-borne encephalitis (TBE), a minority of patients experience long-term neurological deficits. Additionally, 40%–50% of patients develop a post-encephalitic syndrome, which significantly impairs daily activities and quality of life. Although TBEV has been described for several decades, no specific treatment exists. Much remains unknown regarding the objective assessment of long-lasting sequelae. Additional research is needed to better understand, prevent, and treat TBE. In this review, we aim to provide a comprehensive overview of the epidemiology, virology, and clinical picture of TBE.
... Although the use of the licensed TBE vaccines results in high seroconversion rates (11)(12)(13) and is highly effective (14), they fail to afford complete protection against TBEV infection. Reports of breakthrough infections in fully immunized patients are consistently reported (15)(16)(17)(18), and some of these cases even have a fatal outcome (19,20). ...
... TBE is a vaccination-preventable serious disease in humans. Despite the availability of inactivated vaccines, the number of confirmed TBE cases is rising (2, 3), including patients that were fully vaccinated (15)(16)(17)(18)(19)(20). ...
Introduction
Tick-borne encephalitis virus (TBEV) is an important human pathogen that can cause a serious disease involving the central nervous system (tick-borne encephalitis, TBE). Although approved inactivated vaccines are available, the number of TBE cases is rising, and breakthrough infections in fully vaccinated subjects have been reported in recent years.
Methods
In the present study, we generated and characterized a recombinant Modified Vaccinia virus Ankara (MVA) for the delivery of the pre-membrane (prM) and envelope (E) proteins of TBEV (MVA-prME).
Results
MVA-prME was tested in mice in comparison with a licensed vaccine FSME-IMMUN® and proved to be highly immunogenic and afforded full protection against challenge infection with TBEV.
Discussion
Our data indicate that MVA-prME holds promise as an improved next-generation vaccine for the prevention of TBE.
... Several fatal cases of TBE have been described in immunocompromised patients ( Table 2 in supplementary file). Factors, that decreased patients immunity, were among other medications for autoimmunological disorders (Knight et al., al.,2017;Steininger et al., 2017;Sendi et al., 2017;De Bruijn et al., 2015;Zajkowska et al., 2011). TBEV can be a potential threat to organ transplant recipients. ...
... The disease can be effectively prevented by vaccination. However, a standard TBEV vaccine schedule may not provide enough cellular immunogenicity in immunosuppressed patients, and TBE can occur even with a full course of vaccination (Sendi et al., 2017). In a study conducted by Hertzell et al. (2016), post-vaccine levels of neutralizing antibodies against TBE virus were evaluated in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors and/or methotrexate when compared with healthy matched controls. ...
... However the majority of cases were observed among patients over 50 years old [38,39]. The severity of observed cases ranges from mild to severe with sometimes long-term neurological sequelae or even a fatal outcome [38,40]. It is also worth noticing that patients with autoimmune diseases, those who are HIV positive and children after thymectomy also present a lowered serological response to the TBE vaccine [41,42]. ...
In Poland, tick-borne encephalitis (TBE) vaccination rate is low despite high incidence of severe infections with TBE virus (TBEV). However, infection with TBEV can be asymptomatic or mild, which makes the total number of cases difficult to assess. We aimed at assessing asymptomatic TBEV infections and describing attitudes towards the TBE vaccine. We studied 298 healthy adult blood donors and 180 children from the TBE endemic area of northeastern Poland for the presence of anti-TBEV IgG antibodies. We also surveyed a separate cohort of 444 adults. Thirty-eight blood donors (13%) and 38 survey respondents (9%) reported a history of a prior anti-TBEV vaccination. Forty respondents (9%) reported vaccinating their child in the past. Fourteen unvaccinated blood donors (5%) and four children (2%) were seropositive for specific anti-TBEV antibodies, suggesting a history of an undiagnosed TBEV infection. In the surveyed cohort, 130 (32%) expressed their intention to be vaccinated and 144 (36%) expressed their intention to vaccinate their child. This intention was significantly higher in respondents with a recent tick-bite, a diagnosis of tick-borne disease in a close relative, and in males. Our study shows that asymptomatic TBEV infections are common. The acceptance of TBE vaccine is low, but might be increased by communicating risks associated with tick bites.
... Although an effective vaccine is available, the vaccination rate is low in some endemic countries, including Poland (Erber and Schmitt, 2018). What is more, immunocompromised/immunosuppressed patients and those with some comorbid diseases cannot fully response to vaccination against TBE (Sendi et al., 2017). In the presented case the used treatment was empirical. ...
Northeastern Poland is an endemic region for tick-borne encephalitis (TBE). The COVID-19 pandemic overlapped with the activity period of ticks that are the main vectors for TBE. As we know from short observation worldwide, SARS-CoV-2 virus affects significantly the immune system and can lead to serious complications of other infections even in previously healthy patients. A 24-year-old female patient, who lived close to the forest, was admitted to the Department of Neurology at Medical University of Bialystok with fever, dizziness, and progressive left-sided hemiparesis for three days. She had no medical history of chronic disease and was not vaccinated against TBE. The patient had SARS-CoV-2 infection three weeks prior to admission to the hospital (positive IgG against SARS-CoV-2). During COVID-19 infection she had fever, myalgia, a mild dyspnoea without indications for oxygen therapy and recovered after one week. During hospitalisation in the Department of Neurology the patient presented neck stiffness, progressing tetraparesis, dysarthria and weakness of the neck muscles. The magnetic resonance of the head revealed numerous lesions, mainly in both thalamus, longitudinal lesion was found in the cervical spinal cord. The ce-rebrospinal fluid analysis indicated lymphocytic inflammation. A high level of TBE antibodies in both serum and CSF was found. After immunoglobulin and symptomatic treatment her condition gradually improved. The recovery after SARS-CoV-2 infection overlapping with TBE might have influenced the course of tick-borne disease in a bad manner. The correct diagnosis can be a challenge as COVID-19 can lead to further complications, also neurological. The coincidence we observed is very rare, however during the pandemic it is pivotal to remember about possible occurrence of other infections and their atypical course.
... Although an effective vaccine is available, the vaccination rate is low in some endemic countries, including Poland (Erber and Schmitt, 2018). What is more, immunocompromised/immunosuppressed patients and those with some comorbid diseases cannot fully response to vaccination against TBE (Sendi et al., 2017). In the presented case the used treatment was empirical. ...
North-eastern Poland is an endemic region for tick-borne encephalitis (TBE). The COVID-19 pandemic overlapped with the activity period of ticks that are the main vectors for TBE. As we know from short observation worldwide, SARS-CoV-2 virus affects significantly the immune system and can lead to serious complications of other infections even in previously healthy patients.
A 24-year-old female patient, who lived close to the forest, was admitted to the Department of Neurology at Medical University of Bialystok with fever, dizziness, and progressive left-sided hemiparesis for three days. She had no medical history of chronic disease and was not vaccinated against TBE. The patient had SARS-CoV-2 infection three weeks prior to admission to the hospital (positive IgG against SARS-CoV-2). During COVID-19 infection she had fever, myalgia, a mild dyspnoea without indications for oxygen therapy and recovered after one week. During hospitalisation in the Department of Neurology the patient presented neck stiffness, progressing tetraparesis, dysarthria and weakness of the neck muscles. The magnetic resonance of the head revealed numerous lesions, mainly in both thalamus, longitudinal lesion was found in the cervical spinal cord. The cerebrospinal fluid analysis indicated lymphocytic inflammation. A high level of TBE antibodies in both serum and CSF was found. After immunoglobulin and symptomatic treatment her condition gradually improved. The recovery after SARS-CoV-2 infection overlapping with TBE might have influenced the course of tick-borne disease in a bad manner. The correct diagnosis can be a challenge as COVID-19 can lead to further complications, also neurological. The co-incidence we observed is very rare, however during the pandemic it is pivotal to remember about possible occurrence of other infections and their atypical course.
