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  1. Article: Seroprevalence and Risk Factors Associated with Phleboviruses and Crimean-Congo Hemorrhagic Fever Virus among Blood Donors in Central Tunisia.

    Ayari, Rym / Chaouch, Houda / Findlay-Wilson, Stephen / Hachfi, Wissem / Ben Lasfar, Nadia / Bellazreg, Foued / Dowall, Stuart / Hannachi, Neila / Letaief, Amel

    Pathogens (Basel, Switzerland)

    2024  Volume 13, Issue 4

    Abstract: The aim of this study was to determine the prevalence of six viruses, from two families of the ... ...

    Abstract The aim of this study was to determine the prevalence of six viruses, from two families of the order
    Language English
    Publishing date 2024-04-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens13040348
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Detection of tick-borne encephalitis virus in the UK.

    Holding, Maya / Dowall, Stuart / Hewson, Roger

    Lancet (London, England)

    2020  Volume 395, Issue 10222, Page(s) 411

    MeSH term(s) Antibodies, Viral ; Encephalitis Viruses, Tick-Borne ; United Kingdom
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2020-01-07
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(20)30040-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Use of a Preclinical Natural Transmission Model to Study Antiviral Effects of a Carbohydrate-Binding Module Therapy against SARS-CoV-2 in Hamsters.

    Knott, Daniel / Fell, Rachel / Potter, Jane A / Yuille, Samantha / Salguero, Franscisco J / Graham, Victoria A / Hewson, Roger / Howat, David / Dowall, Stuart D

    Viruses

    2023  Volume 15, Issue 3

    Abstract: The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and its expansion to a worldwide pandemic resulted in efforts to assess and develop interventions to reduce the disease burden. Despite the introduction of vaccine programmes ... ...

    Abstract The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and its expansion to a worldwide pandemic resulted in efforts to assess and develop interventions to reduce the disease burden. Despite the introduction of vaccine programmes against SARS-CoV-2, global incidence levels in early 2022 remained high, demonstrating a need for the development of physiologically relevant models, which are essential for the identification of alternative antiviral strategies. The hamster model of SARS-CoV-2 infection has been widely adopted due to similarities with humans in terms of host cell entry mechanism (via ACE2), and aspects of symptomology and virus shedding. We have previously described a natural transmission hamster model that better represents the natural course of infection. In the present study, we have conducted further testing of the model using the first-in-class antiviral Neumifil, which has previously shown promise against SARS-CoV-2 after a direct intranasal challenge. Neumifil is an intranasally delivered carbohydrate-binding module (CBM) which reduces the binding of viruses to their cellular receptor. By targeting the host cell, Neumifil has the potential to provide broad protection against multiple pathogens and variants. This study demonstrates that using a combination of a prophylactic and therapeutic delivery of Neumifil significantly reduces the severity of clinical signs in animals infected via a natural route of transmission and indicates a reduction of viral loads in the upper respiratory tract. Further refinements of the model are required in order to ensure the adequate transmission of the virus. However, our results provide additional data to the evidence base of Neumifil efficacy against respiratory virus infection and demonstrate that the transmission model is a potentially valuable tool for testing antiviral compounds against SARS-CoV-2.
    MeSH term(s) Animals ; Cricetinae ; Humans ; SARS-CoV-2/metabolism ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Antiviral Agents/chemistry ; COVID-19 ; Carbohydrates
    Chemical Substances Antiviral Agents ; Carbohydrates
    Language English
    Publishing date 2023-03-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15030725
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Establishment of a Nipah Virus Disease Model in Hamsters, including a Comparison of Intranasal and Intraperitoneal Routes of Challenge.

    Findlay-Wilson, Stephen / Flett, Lucy / Salguero, Francisco J / Ruedas-Torres, Ines / Fotheringham, Susan / Easterbrook, Linda / Graham, Victoria / Dowall, Stuart

    Pathogens (Basel, Switzerland)

    2023  Volume 12, Issue 8

    Abstract: Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion ... ...

    Abstract Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through exposure of infected pigs, ingestion of contaminated food, or through contact with an infected person. With no approved treatments or vaccines, NiV poses a threat to human public health and has epidemic potential. To aid with the assessment of emerging interventions being developed, an expansion of preclinical testing capability is required. Given variations in the model parameters observed in different sites during establishment, optimisation of challenge routes and doses is required. Upon evaluating the hamster model, an intranasal route of challenge was compared with intraperitoneal delivery, demonstrating a more rapid dissemination to wider tissues in the latter. A dose effect was observed between those causing respiratory illness and those resulting in neurological disease. The data demonstrate the successful establishment of the hamster model of NiV disease for subsequent use in the evaluation of vaccines and antivirals.
    Language English
    Publishing date 2023-07-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens12080976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Lineage-dependent differences of Zika virus infection in a susceptible mouse model are associated with different profiles of cytokines, chemokines, growth factors and acute phase proteins.

    Dowall, Stuart D / Graham, Victoria A / Hewson, Roger

    Cytokine

    2019  Volume 125, Page(s) 154864

    Abstract: Zika virus (ZIKV) is phylogenetically divided into two lineages comprising African ( ... ...

    Abstract Zika virus (ZIKV) is phylogenetically divided into two lineages comprising African (ZIKV
    MeSH term(s) Acute-Phase Proteins/metabolism ; Animals ; Chemokines/blood ; Chemokines/metabolism ; Cytokines/blood ; Cytokines/metabolism ; Disease Models, Animal ; Disease Progression ; Inflammation/metabolism ; Inflammation/virology ; Intercellular Signaling Peptides and Proteins/blood ; Intercellular Signaling Peptides and Proteins/metabolism ; Male ; Mice ; Receptor, Interferon alpha-beta/deficiency ; Receptor, Interferon alpha-beta/genetics ; Receptor, Interferon alpha-beta/metabolism ; Zika Virus/pathogenicity ; Zika Virus Infection/metabolism ; Zika Virus Infection/physiopathology ; Zika Virus Infection/virology
    Chemical Substances Acute-Phase Proteins ; Chemokines ; Cytokines ; Intercellular Signaling Peptides and Proteins ; Receptor, Interferon alpha-beta (156986-95-7)
    Language English
    Publishing date 2019-09-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2019.154864
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Third International Conference on Crimean-Congo Hemorrhagic Fever in Thessaloniki, Greece, September 19-21, 2023.

    Welch, Stephen R / Garrison, Aura R / Bente, Dennis A / Burt, Felicity / D'Addiego, Jake / Devignot, Stephanie / Dowall, Stuart / Fischer, Kerstin / Hawman, David W / Hewson, Roger / Mirazimi, Ali / Oestereich, Lisa / Vatansever, Zati / Spengler, Jessica R / Papa, Anna

    Antiviral research

    2024  Volume 225, Page(s) 105844

    Abstract: The Third International Conference on Crimean-Congo Hemorrhagic Fever (CCHF) was held in Thessaloniki, Greece, September 19-21, 2023, bringing together a diverse group of international partners, including public health professionals, clinicians, ... ...

    Abstract The Third International Conference on Crimean-Congo Hemorrhagic Fever (CCHF) was held in Thessaloniki, Greece, September 19-21, 2023, bringing together a diverse group of international partners, including public health professionals, clinicians, ecologists, epidemiologists, immunologists, and virologists. The conference was attended by 118 participants representing 24 countries and the World Health Organization (WHO). Meeting sessions covered the epidemiology of CCHF in humans; Crimean-Congo hemorrhagic fever virus (CCHFV) in ticks; wild and domestic animal hosts; molecular virology; pathogenesis and animal models; immune response related to therapeutics; and CCHF prevention in humans. The concluding session focused on recent WHO recommendations regarding disease prevention, control strategies, and innovations against CCHFV outbreaks. This meeting report summarizes lectures by the invited speakers and highlights advances in the field.
    MeSH term(s) Animals ; Humans ; Hemorrhagic Fever, Crimean/epidemiology ; Hemorrhagic Fever Virus, Crimean-Congo ; Greece ; Ticks ; Disease Outbreaks
    Language English
    Publishing date 2024-02-29
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2024.105844
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Use and reliability of multiplex bead-based assays (Luminex) at Containment Level 4.

    Dowall, Stuart D / Graham, Victoria A / Fletcher, Tom / Hewson, Roger

    Methods (San Diego, Calif.)

    2019  Volume 158, Page(s) 17–21

    Abstract: In the UK, research on hazard group 4 (HG4) pathogens requires specialised Containment Level 4 (CL4) facilities. These differ from Biosafety Level 4 (BSL4) conditions in that work is conducted in class III microbiological safety cabinets for primary ... ...

    Abstract In the UK, research on hazard group 4 (HG4) pathogens requires specialised Containment Level 4 (CL4) facilities. These differ from Biosafety Level 4 (BSL4) conditions in that work is conducted in class III microbiological safety cabinets for primary containment instead of using positive pressure suits. This presents unique challenges associated with the physical restrictions of working in a limited space, and prohibits the use of many techniques and specialist equipment. In consequence, detailed studies on the biology of HG4 pathogens and in particular their immunological relationships with the host are understudied in the UK; for example, the majority of immunological assays with which the immune system is interrogated require specialist equipment that is unsuitable for CL4. Multiplexing to simultaneously measure multiple analytes is increasingly being used in immunological studies. This assay is attractive for CL4 work because it reduces the time spent in the laboratory whilst maximising the use of valuable sample volume. The Luminex microsphere approach allows for the determination of many cytokines and chemokines, however, the detection system uses fixed aligned lasers and integrated computer systems which are unsuitable for use at CL4. Therefore, we have developed an approach in which the Luminex assay is conducted within the CL4 laboratory and a formalin-fixation stage is introduced to allow for analysis to be undertaken outside of containment. Quality control preparations allow the assay characteristics to be monitored and analysis of assay performance to be evaluated. Our data demonstrate that Luminex is an applicable tool for use at CL4 and that assays can be run reliably to generate reproducible standardised data across different plates and individual experiments.
    MeSH term(s) Clinical Laboratory Services ; Communicable Diseases/diagnosis ; Communicable Diseases/microbiology ; Containment of Biohazards/standards ; Fixatives/chemistry ; Formaldehyde/chemistry ; High-Throughput Screening Assays/instrumentation ; High-Throughput Screening Assays/methods ; High-Throughput Screening Assays/standards ; Humans ; Laboratories/standards ; Microbiology/standards ; Microspheres ; Quality Control ; Reproducibility of Results ; Tissue Fixation/methods ; Tissue Fixation/standards
    Chemical Substances Fixatives ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2019-02-13
    Publishing country United States
    Document type Journal Article ; Validation Study
    ZDB-ID 1066584-5
    ISSN 1095-9130 ; 1046-2023
    ISSN (online) 1095-9130
    ISSN 1046-2023
    DOI 10.1016/j.ymeth.2019.02.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Development of vaccines against Crimean-Congo haemorrhagic fever virus

    Dowall, Stuart D / Miles W. Carroll / Roger Hewson

    Vaccine. 2017,

    2017  

    Abstract: Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen of the utmost seriousness being highly lethal causing devastating disease symptoms that result in intense and prolonged suffering to those infected. During the past 40years, this ... ...

    Abstract Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen of the utmost seriousness being highly lethal causing devastating disease symptoms that result in intense and prolonged suffering to those infected. During the past 40years, this virus has repeatedly caused sporadic outbreaks responsible for relatively low numbers of human casualties, but with an alarming fatality rate of up to 80% in clinically infected patients. CCHFV is transmitted to humans by Hyalomma ticks and contact with the blood of viremic livestock, additionally cases of human-to-human transmission are not uncommon in nosocomial settings. The incidence of CCHF closely matches the geographical range of permissive ticks, which are widespread throughout Africa, Asia, the Middle East and Europe. As such, CCHFV is the most widespread tick-borne virus on earth. It is a concern that recent data shows the geographic distribution of Hyalomma ticks is expanding. Migratory birds are also disseminating Hyalomma ticks into more northerly parts of Europe thus potentially exposing naïve human populations to CCHFV. The virus has been imported into the UK on two occasions in the last five years with the first fatal case being confirmed in 2012. A licensed vaccine to CCHF is not available. In this review, we discuss the background and complications surrounding this limitation and examine the current status and recent advances in the development of vaccines against CCHFV.
    Keywords animal pathogens ; blood ; Crimean-Congo hemorrhagic fever virus ; cross infection ; geographical distribution ; human population ; humans ; Hyalomma ; livestock ; migratory birds ; mortality ; patients ; ticks ; vaccine development ; vaccines ; viruses ; Africa ; Asia ; Middle East ; United Kingdom
    Language English
    Size p. .
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2017.05.031
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Pathogenesis of Rift Valley Fever Virus in a BALB/c Mouse Model Is Affected by Virus Culture Conditions and Sex of the Animals.

    Graham, Victoria A / Easterbrook, Linda / Kennedy, Emma / Rayner, Emma / Findlay-Wilson, Stephen / Flett, Lucy / Wise, Emma Louise / Treagus, Samantha / Fotheringham, Susan / Kempster, Sarah / Almond, Neil / Dowall, Stuart

    Viruses

    2023  Volume 15, Issue 12

    Abstract: Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new ... ...

    Abstract Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new regions. Due to the absence of a regulatory-approved human vaccine, work is ongoing to develop and assess countermeasures. As such, small animal models play a pivotal role in providing information on disease pathogenesis and elucidating which intervention strategies confer protection. To develop and establish the BALB/c mouse model, we challenged mice with RVFV grown from two separate cell lines: one derived from mosquitoes (C6/36) and the other mammalian derived (Vero E6). Following infection, we assessed the clinical course of disease progression at days 1 and 3 post-challenge and evaluated viral tropism and immune analytes. The results demonstrated that RVFV infection was affected by the cell line used to propagate the challenge virus, with those grown in insect cells resulting in a more rapid disease progression. The lowest dose that caused uniform severe disease remained the same across both virus preparations. In addition, to demonstrate reproducibility, the lowest dose was used for a subsequent infection study using male and female animals. The results further demonstrated that male mice succumbed to infection more rapidly than their female counterparts. Our results establish an RVFV mouse model and key parameters that affect the course of disease progression in BALB/c mice.
    MeSH term(s) Male ; Female ; Humans ; Animals ; Mice ; Rift Valley fever virus ; Rift Valley Fever ; Mice, Inbred BALB C ; Reproducibility of Results ; Disease Progression ; Mammals
    Language English
    Publishing date 2023-11-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15122369
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model.

    Saunders, Jack E / Gilbride, Ciaran / Dowall, Stuart / Morris, Susan / Ulaszewska, Marta / Spencer, Alexandra J / Rayner, Emma / Graham, Victoria A / Kennedy, Emma / Thomas, Kelly / Hewson, Roger / Gilbert, Sarah C / Belij-Rammerstorfer, Sandra / Lambe, Teresa

    EBioMedicine

    2023  Volume 90, Page(s) 104523

    Abstract: Background: The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines ... ...

    Abstract Background: The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines against CCHFV for widespread usage.
    Methods: In this study, we describe the preclinical assessment of a chimpanzee adenoviral vectored vaccine (ChAdOx2 CCHF) which encodes the glycoprotein precursor (GPC) from CCHFV.
    Findings: We demonstrate here that vaccination with ChAdOx2 CCHF induces both a humoral and cellular immune response in mice and 100% protection in a lethal CCHF challenge model. Delivery of the adenoviral vaccine in a heterologous vaccine regimen with a Modified Vaccinia Ankara vaccine (MVA CCHF) induces the highest levels of CCHFV-specific cell-mediated and antibody responses in mice. Histopathological examination and viral load analysis of the tissues of ChAdOx2 CCHF immunised mice reveals an absence of both microscopic changes and viral antigen associated with CCHF infection, further demonstrating protection against disease.
    Interpretation: There is the continued need for an effective vaccine against CCHFV to protect humans from lethal haemorrhagic disease. Our findings support further development of the ChAd platform expressing the CCHFV GPC to seek an effective vaccine against CCHFV.
    Funding: This research was supported by funding from the Biotechnology and Biological Sciences Research Council (UKRI-BBSRC) [BB/R019991/1 and BB/T008784/1].
    MeSH term(s) Humans ; Animals ; Mice ; Hemorrhagic Fever, Crimean/prevention & control ; Hemorrhagic Fever Virus, Crimean-Congo/genetics ; Vaccination ; Viral Vaccines ; Genetic Vectors/genetics ; Vaccinia virus
    Chemical Substances Viral Vaccines
    Language English
    Publishing date 2023-03-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2023.104523
    Database MEDical Literature Analysis and Retrieval System OnLINE

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