BACKGROUND: Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia. Outcomes range from asymptomatic infection to fatal encephalitis, with host genetics likely playing a role. BALB/c mice have intermediate susceptibility to TBE virus (TBEV) and STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, which carries 12.5% of the STS genome on the BALB/c background, is more susceptible than BALB/c mice. In the present study, we employed these genetically distinct mouse models to investigate the host response to TBEV infection in both peripheral macrophages, one of the initial target cell populations, and the brain, the terminal target organ of the virus. METHODS: TBEV growth and the production of key cytokines and chemokines were measured and compared in macrophages derived from BALB/c, CcS-11, and STS mice. In addition, brains from these TBEV-infected mouse strains underwent in-depth transcriptomic analysis. RESULTS: Virus production in BALB/c and CcS-11 macrophages exhibited similar kinetics 24 and 48 h post-infection (hpi), but CcS-11 macrophages yielded significantly higher titers 72 hpi. Macrophages from both sensitive strains demonstrated elevated chemokine and proinflammatory cytokine production upon infection, whereas the resistant strain, STS, showed no cytokine/chemokine activation. Transcriptomic analysis of brain tissue demonstrated that the genetic background of the mouse strains dictated their transcriptional response to infection. The resistant strain exhibited a more robust cell-mediated immune response, whereas both sensitive strains showed a less effective cell-mediated response but increased cytokine signaling and signs of demyelination, with loss of oligodendrocytes. CONCLUSIONS: Our findings suggest that variations in susceptibility linked to host genetic background correspond with distinct host responses, both in the periphery upon virus entry into the organism and in the brain, the target organ of the virus. These results provide insights into the influence of host genetics on the clinical trajectory of TBE.

• Klíčová slova
• Genetics, Macrophages, Mouse model, Neuroinflammation, Tick-borne encephalitis, Tick-borne encephalitis virus, Transcriptomics,
• MeSH
• cytokiny * metabolismus   genetika   MeSH
• genotyp MeSH
• klíšťová encefalitida * imunologie   virologie   genetika   MeSH
• makrofágy * imunologie   virologie   MeSH
• mozek * virologie   imunologie   MeSH
• myši inbrední BALB C * MeSH
• myši MeSH
• viry klíšťové encefalitidy * genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny * MeSH

Tick-borne encephalitis virus (TBEV) is flavivirus transmitted to the host via tick saliva which contains various molecules with biological impacts. One of such molecules is Iristatin, a cysteine protease inhibitor from Ixodes ricinus that has been shown to have immunomodulatory properties. To characterize Iristatin in the relation to TBEV, we investigate whether this tick inhibitor has any capacity to influence TBEV infection. Mice were intradermally infected by TBEV with or without Iristatin and the viral multiplication was determined in skin and brain tissues by RT-PCR two and 5 days after infection. The viral RNA was detected in both intervals in skin and increased by time. The application of Iristatin caused a reduction in viral RNA in skin but not in the brain of infected mice 5 days post-infection. Moreover, anti-viral effect of Iristatin on skin was accompanied by a significant decline of interferon-stimulated gene 15 gene expression. The effect of Iristatin on TBEV replication was tested also in vitro in primary macrophages and dendritic cells; however, no changes were observed suggesting no direct interference of Iristatin with virus replication. Still, the Iristatin caused a suppression of Erk1/2 phosphorylation in TBEV-infected dendritic cells and had the anti-apoptotic effect. This is the first report showing that a tick cystatin decreases the viral RNA in the host skin, likely indirectly through creating skin environment that is less supportive for TBEV replication. Assuming, that viral RNA reflects the amount of infectious virus, decline of TBEV in host skin could influence the tick biology or virus transmission during cofeeding.

• Klíčová slova
• Cystatin, Flavivirus, Tick, Tick-borne encephalitis virus, Virus replication,
• MeSH
• antivirové látky farmakologie   MeSH
• cystatiny farmakologie   metabolismus   genetika   MeSH
• dendritické buňky virologie   účinky léků   MeSH
• klíště * virologie   účinky léků   MeSH
• klíšťová encefalitida * virologie   MeSH
• kůže * virologie   MeSH
• makrofágy virologie   MeSH
• mozek virologie   metabolismus   MeSH
• myši MeSH
• replikace viru * účinky léků   MeSH
• RNA virová genetika   MeSH
• slinné cystatiny metabolismus   MeSH
• viry klíšťové encefalitidy * účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• cystatiny MeSH
• RNA virová MeSH
• slinné cystatiny MeSH

The European subtype of tick-borne encephalitis virus (TBEV-Eur; species Orthoflavivirus encephalitidis, family Flaviviridae) was the only tick-borne flavivirus present in central Europe known to cause neurologic disease in humans and several animal species. Here, we report a tick-borne flavivirus isolated from Alpine chamois (Rupicapra rupicapra rupicapra) with encephalitis and attached ticks, present over a wide area in the Alps. Cases were detected in 2017 in Salzburg, Austria, and 2023 in Lombardy and Piedmont, Italy. The virus strains exhibit 94.8-97.3% nucleotide identities to each other and are more closely related to Louping ill viruses (LIV; Orthoflavivirus loupingi; 90-92% identities) than to TBEV-Eur (less than 88%). The chamois-derived virus strains, tentatively termed "Alpine chamois encephalitis virus", form a well-supported independent genetic clade with Spanish goat encephalitis virus, clearly separated from other LIV. This supports its designation as a new virus subtype with the proposed shared taxonomic name "Spanish goat and Alpine chamois encephalitis virus subtype" within the species Orthoflavivirus loupingi. The zoonotic potential of this newly identified virus subtype as well as its host range in other animal species including farm animals needs to be further investigated.

• Klíčová slova
• Alpine chamois, Flaviviridae, Ixodes ricinus, Rupicapra rupicapra, Spanish goat encephalitis virus, encephalitis, flavivirus, louping ill virus, neurotropic, tick-borne encephalitis virus,
• MeSH
• Flavivirus izolace a purifikace   klasifikace   genetika   MeSH
• fylogeneze * MeSH
• genom virový MeSH
• infekce viry z rodu Flavivirus veterinární   virologie   epidemiologie   MeSH
• klíšťata virologie   MeSH
• klíšťová encefalitida virologie   MeSH
• nemoci koz virologie   MeSH
• Rupicapra * virologie   MeSH
• viry klíšťové encefalitidy * izolace a purifikace   klasifikace   genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Itálie MeSH
• Rakousko MeSH

Categorization systems for tick-borne encephalitis virus (TBEV) infection lack consistency in classifying disease severity. To evaluate the need for a standard, consensus-based categorisation system for TBEV infection across subtypes, we gathered an expert panel of clinicians and scientists with diverse expertise in TBEV infection. Consensus was sought using the Delphi technique, which consisted of 2 web-based survey questionnaires and a final, virtual, consensus-building exercise. Ten panellists representing 8 European countries participated in the Delphi exercise, with specialities in neurology, infectious disease, paediatrics, immunology, virology, and epidemiology. Panellists reached unanimous consensus on the need for a standardised, international categorisation system to capture both clinical presentation and severity of TBEV infection. Ideally, such a system should be feasible for use at bedside, be clear and easy to understand, and capture both the acute and follow-up phases of TBEV infection. Areas requiring further discussion were (1) the timepoints at which assessments should be made and (2) whether there should be a separate system for children. This Delphi panel study found that a critical gap persists in the absence of a feasible and practical classification system for TBEV infection. Specifically, the findings of our Delphi exercise highlight the need for the development of a user-friendly classification system that captures the acute and follow-up (i.e., outcome) phases of TBEV infection and optimally reflects both clinical presentation and severity. Development of a clinical categorisation system will enhance patient care and foster comparability among studies, thereby supporting treatment development, refining vaccine strategies, and fortifying public health surveillance.

• Klíčová slova
• Categorisation, Delphi panel, Disease severity, Tick-borne encephalitis,
• MeSH
• delfská metoda * MeSH
• klíšťová encefalitida * epidemiologie   virologie   diagnóza   MeSH
• konsensus MeSH
• lidé MeSH
• viry klíšťové encefalitidy * klasifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

AIM: Aim of the pilot was to increase HIV/HCV/syphilis testing and linkage to care of newly diagnosed persons, improve data collection and transfer using standard data collection tools in CBVCT services. METHODS: Integrated anonymous voluntary testing from blood for HIV, HCV and syphilis was realised using rapid tests in the period of 6 months (03/2019-08/2019). Participants with reactive results were advised to see a specialist for confirmatory testing and/or treatment. RESULTS: A total of 675 clients were tested for HIV, 410 for HCV, and 457 for syphilis. Participants' median age ranged from 24 to 35.6 (IQR: 24), 75.3% of them were men, 23.7% were women, and 0.6% identified as transgender. In terms of groups at risk 48.9 % of 675 clients were men who have sex with men (MSM), 0.3 % sex workers (SW), 9.0 % people who inject drugs (PWID), 2.4 % migrants (Mi) and the rest of clients (8.3 %) belonged to groups at combined risk. Pilot revealed HIV, HCV and T. pallidum infections in 0.4 %, 2.4 % and 1.8 % of clients, respectively. Just 2 clients, confirmed HIV-positive, were linked to care. The highest prevalence of HIV (4.2 %), HCV (30.8 %) and syphilis (7.1 %) was found among MSM/Mi, PWID and SW/PWID, respectively. Condomless intercourse with SW, PWID, MSM and HIV-positive person in the last 12 months was reported by 5/92, 41/82, 3/78 and 0/88 of responding clients, respectively. Core indicators were included in the yearly national epidemiological report. CONCLUSIONS: Pilot revealed the need to support integrated CBVCT to overcome barriers in confirmatory testing and linkage to care and to integrate core data of monitoring and evaluation (M&E) testing framework at CBVCT services into a national surveillance and M&E systems in Slovakia.

• Klíčová slova
• HCV, HIV, Slovakia, Syphilis, integrated testing, secular trends,
• MeSH
• dospělí MeSH
• hepatitida C * diagnóza   epidemiologie   MeSH
• HIV infekce * diagnóza   epidemiologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• pilotní projekty MeSH
• plošný screening metody   MeSH
• poradenství MeSH
• syfilis * diagnóza   epidemiologie   MeSH
• testování na HIV metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika epidemiologie   MeSH

Extensive research has been conducted on the SARS-CoV-2 virus in association with various infectious diseases to understand the pathophysiology of the infection and potential co-infections. In tropical countries, exposure to local viruses may alter the course of SARS-CoV-2 infection and coinfection. Notably, only a portion of the antibodies produced against SARS-CoV-2 proteins demonstrate neutralizing properties, and the immune response following natural infection tends to be temporary. In contrast, long-lasting IgG antibodies are common after dengue virus infections. In cases where preexisting antibodies from an initial dengue virus infection bind to a different dengue serotype during a subsequent infection, there is a potential for antibody-dependent enhancement (ADE) and the formation of immune complexes associated with disease severity. Both SARS-CoV-2 and dengue infections can result in immunodeficiency. Viral proteins of both viruses interfere with the host's IFN-I signaling. Additionally, a cytokine storm can occur after viral infection, impairing a proper response, and autoantibodies against a wide array of proteins can appear during convalescence. Most of the reported autoantibodies are typically short-lived. Vaccines against both viruses alter the immune response, affecting the course of viral infection and enhancing clearance. A comprehensive analysis of both viral infections and pathogenicity is revisited to prevent infection, severity, and mortality.

• Klíčová slova
• COVID-19, SARS-CoV-2 infection, antibodies, antibody-dependent enhancement (ADE), cytokine storm, dengue infection, platelets,
• MeSH
• COVID-19 * imunologie   virologie   MeSH
• dengue * imunologie   virologie   MeSH
• koinfekce imunologie   virologie   MeSH
• lidé MeSH
• protilátky virové * imunologie   MeSH
• SARS-CoV-2 * imunologie   MeSH
• virus dengue * imunologie   MeSH
• zvýšená infektivita v přítomnosti protilátek imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protilátky virové * MeSH

INTRODUCTION: This work focuses on the Dengue-viremia ABC (Atangana-Baleanu Caputo) fractional-order differential equations, accounting for both symptomatic and asymptomatic infected cases. Symptomatic cases are characterized by higher viremia levels, whereas asymptomatic cases exhibit lower viremia levels. The fractional-order model highlights memory effects and other advantages over traditional models, offering a more comprehensive representation of dengue dynamics. METHODS: The total population is divided into four compartments: susceptible, asymptomatic infected, symptomatic infected, and recovered. The model incorporates an immune-boosting factor for asymptomatic infected individuals and clinical treatment for symptomatic cases. Positivity and boundedness of the model are validated, and both local and global stability analyses are performed. The novel Adams-Bash numerical scheme is utilized for simulations to rigorously assess the impact of optimal control interventions. RESULTS: The results demonstrate the effectiveness of the proposed control strategies. The reproduction numbers must be reduced based on specific optimal control conditions to effectively mitigate disease outbreaks. Numerical simulations confirm that the optimal control measures can significantly reduce the spread of the disease. DISCUSSION: This research advances the understanding of Dengue-viremia dynamics and provides valuable insights into the application of ABC fractional-order analysis. By incorporating immune-boosting and clinical treatment into the model, the study offers practical guidelines for implementing successful disease control strategies. The findings highlight the potential of using optimal control techniques in public health interventions to manage disease outbreaks more effectively.

• Klíčová slova
• Adams-Bashforth method, Atangana-Baleanu operator, Lyapunov stability, basic reproduction value, dengue fractional-order mathematical modeling, optimal control,
• MeSH
• dengue * MeSH
• epidemický výskyt choroby MeSH
• lidé MeSH
• viremie * MeSH
• virus dengue imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.

• MeSH
• autoprotilátky * imunologie   MeSH
• dospělí MeSH
• interferon typ I * imunologie   MeSH
• klíšťová encefalitida * imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutralizující protilátky * imunologie   MeSH
• senioři MeSH
• viry klíšťové encefalitidy imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Rakousko epidemiologie   MeSH
• Názvy látek
• autoprotilátky * MeSH
• interferon typ I * MeSH
• neutralizující protilátky * MeSH

Background: Tick-borne encephalitis (TBE) is caused by the tick-borne encephalitis virus (TBEV). TBEV infection can cause symptoms of central nervous system (CNS) inflammation and result in severe consequences including death. TBE is an increasing health threat in the Czech Republic and elsewhere in Europe. In 2020, 23% of 3734 TBE cases reported to the European Centre for Disease Prevention and Control were from the Czech Republic. TBE vaccination is universally recommended in the Czech Republic, but a full analysis of TBE vaccine effectiveness (VE) in the Czech Republic has not been published. Methods: TBE is a notifiable disease in the Czech Republic with mandatory reporting of cases (i.e., laboratory-confirmed TBEV infected patient with symptoms of CNS inflammation) and vaccination history to public health authorities. TBE VE was estimated using the screening method utilizing public health surveillance data from 2018 to 2022 and online household surveys of the general population on TBE vaccine uptake conducted in 2019-2022. Results: In 2018-2022, 3648 TBE cases were reported in the Czech Republic; 98.1% (3105/3166) of TBE cases with known vaccination history were unvaccinated. Among 42,671 persons surveyed from the general population who had known TBE vaccination history, 66.5% were unvaccinated. VE against TBE was 97.6% (95% confidence interval 95.7-98.7). When stratified by age group, VE was 97.1% (88.4-99.3) in 1-15 years of age, 97.9% (95.3-99.0) in 16-59 years of age, and 96.9% (90.5-99.0) in ≥60 years of age. TBE vaccination averted an estimated 1020 TBE cases in the Czech Republic from 2018 to 2022. Conclusions: This first published study with a full analysis of TBE VE in the Czech Republic showed that vaccination was highly effective for the prevention of TBE including in children, an age group with increasing TBE disease burden. Vaccination averted hundreds of TBE cases and hospitalizations despite the relatively low compliance with TBE vaccine recommendations. To prevent additional TBE cases in the Czech Republic, enhanced efforts to increase TBE vaccine uptake are needed.

• Klíčová slova
• epidemiology, prevention, surveillance, vector-borne disease,
• MeSH
• dítě MeSH
• dospělí MeSH
• klíšťová encefalitida * prevence a kontrola   epidemiologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• senioři MeSH
• vakcinace * MeSH
• virové vakcíny * aplikace a dávkování   MeSH
• viry klíšťové encefalitidy * imunologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• virové vakcíny * MeSH

Ticks are important vectors of disease, particularly in the context of One Health, where tick-borne diseases (TBDs) are increasingly prevalent worldwide. TBDs often involve co-infections, where multiple pathogens co-exist in a single host. Patients with chronic Lyme disease often have co-infections with other bacteria or parasites. This study aimed to create a co-infection model with Borrelia afzelii and tick-borne encephalitis virus (TBEV) in C3H mice and to evaluate symptoms, mortality, and pathogen level compared to single infections. Successful co-infection of C3H mice with B. afzelii and TBEV was achieved. Outcomes varied, depending on the timing of infection. When TBEV infection followed B. afzelii infection by 9 days, TBEV symptoms worsened and virus levels increased. Conversely, mice infected 21 days apart with TBEV showed milder symptoms and lower mortality. Simultaneous infection resulted in mild symptoms and no deaths. However, our model did not effectively infect ticks with TBEV, possibly due to suboptimal dosing, highlighting the challenges of replicating natural conditions. Understanding the consequences of co-infection is crucial, given the increasing prevalence of TBD. Co-infected individuals may experience exacerbated symptoms, highlighting the need for a comprehensive understanding through refined animal models. This study advances knowledge of TBD and highlights the importance of exploring co-infection dynamics in host-pathogen interactions.

• Klíčová slova
• C3H mice, co-infection, pathogen fitness, pathogen invasiveness, tick-borne pathogens,
• MeSH
• Borrelia burgdorferi komplex MeSH
• klíšťová encefalitida * virologie   MeSH
• koinfekce * mikrobiologie   virologie   MeSH
• lymeská nemoc * mikrobiologie   MeSH
• modely nemocí na zvířatech * MeSH
• myši inbrední C3H * MeSH
• myši MeSH
• viry klíšťové encefalitidy * fyziologie   patogenita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH