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  • Journal article
    Birrell PJ, Zhang X-S, Corbella A, van Leeuwen E, Panagiotopoulos N, Hoschler K, Elliot AJ, McGee M, Lusignan SD, Presanis AM, Baguelin M, Zambon M, Charlett A, Pebody RG, Angelis DDet al., 2020,

    Forecasting the 2017/2018 seasonal influenza epidemic in England using multiple dynamic transmission models: a case study

    , BMC Public Health, Vol: 20, ISSN: 1471-2458

    BACKGROUND: Since the 2009 A/H1N1 pandemic, Public Health England have developed a suite of real-time statistical models utilising enhanced pandemic surveillance data to nowcast and forecast a future pandemic. Their ability to track seasonal influenza and predict heightened winter healthcare burden in the light of high activity in Australia in 2017 was untested. METHODS: Four transmission models were used in forecasting the 2017/2018 seasonal influenza epidemic in England: a stratified primary care model using daily, region-specific, counts and virological swab positivity of influenza-like illness consultations in general practice (GP); a strain-specific (SS) model using weekly, national GP ILI and virological data; an intensive care model (ICU) using reports of ICU influenza admissions; and a synthesis model that included all data sources. For the first 12 weeks of 2018, each model was applied to the latest data to provide estimates of epidemic parameters and short-term influenza forecasts. The added value of pre-season population susceptibility data was explored. RESULTS: The combined results provided valuable nowcasts of the state of the epidemic. Short-term predictions of burden on primary and secondary health services were initially highly variable before reaching consensus beyond the observed peaks in activity between weeks 3-4 of 2018. Estimates for R0 were consistent over time for three of the four models until week 12 of 2018, and there was consistency in the estimation of R0 across the SPC and SS models, and in the ICU attack rates estimated by the ICU and the synthesis model. Estimation and predictions varied according to the assumed levels of pre-season immunity. CONCLUSIONS: This exercise successfully applied a range of pandemic models to seasonal influenza. Forecasting early in the season remains challenging but represents a crucially important activity to inform planning. Improved knowledge of pre-existing levels of immunity would be valuable.

  • Journal article
    Lalvani A, Seshadri C, 2020,

    Understanding how BCG vaccine protects against Mycobacterium tuberculosis infection: Lessons from household contact studies

    , Journal of Infectious Diseases, Vol: 221, Pages: 1229-1231, ISSN: 0022-1899
  • Journal article
    Lee LYY, Zhou J, Frise R, Goldhill DH, Koszalka P, Mifsud EJ, Baba K, Noda T, Ando Y, Sato K, Yuki A-I, Shishido T, Uehara T, Wildum S, Zwanziger E, Collinson N, Kuhlbusch K, Clinch B, Hurt AC, Barclay WSet al., 2020,

    Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission

    , PLOS PATHOGENS, Vol: 16, ISSN: 1553-7366
  • Journal article
    Hoschler K, Maharjan S, Whitaker H, Southern J, Okai B, Baldevarona J, Turner PJ, Andrews NJ, Miller E, Zambon Met al., 2020,

    Use of traditional serological methods and oral fluids to assess immunogenicity in children aged 2-16 years after successive annual vaccinations with LAIV.

    , Vaccine, Vol: 38, Pages: 2660-2670, ISSN: 0264-410X

    BACKGROUND: The UK introduced quadrivalent live attenuated influenza vaccine (qLAIV) for children in 2013/2014. The impact of annual vaccination on effectiveness and immunogenicity is being assessed. METHOD: A phase III/IV open-label study of the immunogenicity of annual vaccination with qLAIV (Fluenz™) was conducted over three consecutive years (2014/15-2016/17) in 254, 249 and 162 children respectively. Serum responses to vaccine components were measured by Haemagglutination Inhibition (HAI) and anti-A(H1N1)pdm09 Neuraminidase (NAI) assays, stratified according to previous receipt of AS03B-adjuvanted A(H1N1)pdm09 pandemic vaccine in 2009/10. Antibody levels to the A(H1N1)pdm09 and H3N2 vaccine components in oral fluids (OF) were explored using an ELISA. FINDINGS: More paired pre- and post-vaccination oral fluids (96%) than paired sera (87%) were obtained. Geometric mean titre rises using HAI assays were limited, with maximum rises seen in year one for both influenza B strains when 39% and 43% of subjects seroconverted (95% confidence interval 33-46% and 36-50%, respectively) and year two for influenza H3N2, when 40% (33-46%) individuals seroconverted. Prior pandemic vaccine receipt resulted in higher pre- and post-vaccination A(H1N1)pdm09 HAI titres and lower pre-and post-vaccination NAI (N1 neuraminidase) titres in all three years. OF results were congruent with HAI results; assay specificity compared to HAI was 88.1 and 71.6 percent, and sensitivity was 86.4 and 74.8 percent respectively for A(H1N1)pdm09 and H3N2. CONCLUSION: In all three study years, vaccination with qLAIV resulted in poor antibody responses. However, OFs are an alternative specimen type that allows self sampling, can easily be obtained from children, and their analysis leads to similar conclusions as classic serology by HAI. Their suitability for seroprevalence studies should be investigated. We demonstrated a sustained effect from prior receipt of the AS03B-adjuvanted A(H1N1)pdm09 vacci

  • Journal article
    Quijano-Campos JC, Williams L, Agarwal S, Tweed K, Parker R, Lalvani A, Chiu Y-D, Dorey K, Devine T, Stoneman V, Toshner M, Thillai Met al., 2020,

    CASPA (CArdiac Sarcoidosis in PApworth) improving the diagnosis of cardiac involvement in patients with pulmonary sarcoidosis: protocol for a prospective observational cohort study

    , BMJ OPEN RESPIRATORY RESEARCH, Vol: 7
  • Journal article
    Jeon D, 2020,

    Latent tuberculosis infection: recent progress and challenges in South Korea

    , KOREAN JOURNAL OF INTERNAL MEDICINE, Vol: 35, Pages: 269-275, ISSN: 1226-3303
  • Journal article
    Mistry B, Long JS, Schreyer J, Staller E, Sanchez-David RY, Barclay WSet al., 2020,

    Elucidating the Interactions between Influenza Virus Polymerase and Host Factor ANP32A

    , JOURNAL OF VIROLOGY, Vol: 94, ISSN: 0022-538X
  • Journal article
    Katelaris AL, Jackson C, Southern J, Gupta RK, Drobniewski F, Lalvani A, Lipman M, Mangtani P, Abubakar Iet al., 2020,

    Effectiveness of BCG vaccination against Mycobacterium tuberculosis infection in adults: a cross-sectional analysis of a UK-based cohort

    , The Journal of Infectious Diseases, Vol: 221, Pages: 146-155, ISSN: 0022-1899

    BackgroundBCG appears to reduce acquisition of Mycobacterium tuberculosis (Mtb) infection in children, measured using interferon-gamma release assays (IGRAs). We explored whether BCG vaccination continues to be associated with decreased prevalence of Mtb infection in adults.MethodsWe conducted a cross-sectional analysis of data from adult contacts of tuberculosis cases participating in a UK cohort study. Vaccine effectiveness (VE) of BCG, ascertained based on presence of a scar or vaccination history, against latent tuberculosis infection (LTBI), measured via IGRA, was assessed using multivariable logistic regression. The effects of age at BCG and time since vaccination were also explored.ResultsOf 3453 recent tuberculosis contacts, 27.5% had LTBI. There was strong evidence of an association between BCG and LTBI (aOR=0.70, 95% CI 0.56-0.87, p=0.0017) yielding a VE of 30%. VE declined with time since vaccination, but there was evidence that LTBI prevalence was lower amongst vaccinated individuals even >20 years after vaccination, compared with non-vaccinated participants.ConclusionBCG is associated with lower prevalence of LTBI in adult contacts of tuberculosis. These results contribute to growing evidence that suggests BCG may protect against Mtb infection as well as disease. This has implications for immunisation programmes, vaccine development and tuberculosis control efforts worldwide.

  • Journal article
    Bhatia S, Imai N, Cuomo-Dannenburg G, Baguelin M, Boonyasiri A, Cori A, Cucunubá Z, Dorigatti I, FitzJohn R, Fu H, Gaythorpe K, Ghani A, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Okell L, Riley S, Thompson H, van Elsland S, Volz E, Wang H, Wang Y, Whittaker C, Xi X, Donnelly CA, Ferguson NMet al., 2020,

    Estimating the number of undetected COVID-19 cases among travellers from mainland China.

    , Wellcome open research, Vol: 5, Pages: 143-143, ISSN: 2398-502X

    Background: As of August 2021, every region of the world has been affected by the COVID-19 pandemic, with more than 196,000,000 cases worldwide.Methods: We analysed COVID-19 cases among travellers from mainland China to different regions and countries, comparing the region- and country-specific rates of detected and confirmed cases per flight volume to estimate the relative sensitivity of surveillance in different regions and countries.Results: Although travel restrictions from Wuhan City and other cities across China may have reduced the absolute number of travellers to and from China, we estimated that up to 70% (95% CI: 54% - 80%) of imported cases could remain undetected relative to the sensitivity of surveillance in Singapore. The percentage of undetected imported cases rises to 75% (95% CI 66% - 82%) when comparing to the surveillance sensitivity in multiple countries.Conclusions: Our analysis shows that a large number of COVID-19 cases remain undetected across the world. These undetected cases potentially resulted in multiple chains of human-to-human transmission outside mainland China.

  • Journal article
    Riley S, Atchison C, Ashby D, Donnelly CA, Barclay W, Cooke GS, Ward H, Darzi A, Elliott P, REACT study groupet al., 2020,

    REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol.

    , Wellcome Open Res, Vol: 5, ISSN: 2398-502X

    Background: England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. Protocol: The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). Ethics and dissemination: The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. Conclusions: This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered testing for SARS-CoV-2 antibody in a home-based setting, not done before at

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