141 results on '"Leon Danon"'
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2. Combined multiplex panel test results are a poor estimate of disease prevalence without adjustment for test error.
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Robert Challen, Anastasia Chatzilena, George Qian, Glenda Oben, Rachel Kwiatkowska, Catherine Hyams, Adam Finn, Krasimira Tsaneva-Atanasova, and Leon Danon
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Biology (General) ,QH301-705.5 - Abstract
Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is detecting causative pathogens for a single syndrome or disease then we might estimate the burden of that disease by combining the results of the panel, for example determining the prevalence of pneumococcal pneumonia as caused by many individual pneumococcal serotypes. When we are dealing with multiplex test panels with many components, test error in the individual components of a panel, even when present at very low levels, can cause significant overall error. Uncertainty in the sensitivity and specificity of the individual tests, and statistical fluctuations in the numbers of false positives and false negatives, will cause large uncertainty in the combined estimates of disease prevalence. In many cases this can be a source of significant bias. In this paper we develop a mathematical framework to characterise this issue, we determine expressions for the sensitivity and specificity of panel tests. In this we identify a counter-intuitive relationship between panel test sensitivity and disease prevalence that means panel tests become more sensitive as prevalence increases. We present novel statistical methods that adjust for bias and quantify uncertainty in prevalence estimates from panel tests, and use simulations to test these methods. As multiplex testing becomes more commonly used for screening in routine clinical practice, accumulation of test error due to the combination of large numbers of test results needs to be identified and corrected for.
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- 2024
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3. Serotype Distribution and Disease Severity in Adults Hospitalized with Streptococcus pneumoniae Infection, Bristol and Bath, UK, 2006‒2022
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Catherine Hyams, Robert Challen, David Hettle, Zahin Amin-Chowdhury, Charli Grimes, Gabriella Ruffino, Rauri Conway, Robyn Heath, Paul North, Adam Malin, Nick A. Maskell, Philip Williams, O. Martin Williams, Shamez N. Ladhani, Leon Danon, and Adam Finn
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pneumonia ,Streptococcus pneumoniae ,bacteria ,pneumococcus ,serotypes ,serotype distribution ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report serotype and disease severity trends in 3,719 adults hospitalized for pneumococcal disease in Bristol and Bath, United Kingdom, during 2006–2022. Of those cases, 1,686 were invasive pneumococcal disease (IPD); 1,501 (89.0%) had a known serotype. IPD decreased during the early COVID-19 pandemic but during 2022 gradually returned to prepandemic levels. Disease severity changed throughout this period: CURB65 severity scores and inpatient deaths decreased and ICU admissions increased. PCV7 and PCV13 serotype IPD decreased from 2006–2009 to 2021–2022. However, residual PCV13 serotype IPD remained, representing 21.7% of 2021–2022 cases, indicating that major adult PCV serotype disease still occurs despite 17 years of pediatric PCV use. Percentages of serotype 3 and 8 IPD increased, and 19F and 19A reemerged. In 2020–2022, a total of 68.2% IPD cases were potentially covered by PCV20.
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- 2023
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4. Robust smoothing of left-censored time series data with a dynamic linear model to infer SARS-CoV-2 RNA concentrations in wastewater
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Luke Lewis-Borrell, Jessica Irving, Chris J. Lilley, Marie Courbariaux, Gregory Nuel, Leon Danon, Kathleen M. O'Reilly, Jasmine M. S. Grimsley, Matthew J. Wade, and Stefan Siegert
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dynamic linear model ,wastewater-based epidemiology ,covid-19 ,time series ,left-censoring ,bayesian inference ,Mathematics ,QA1-939 - Abstract
Wastewater sampling for the detection and monitoring of SARS-CoV-2 has been developed and applied at an unprecedented pace, however uncertainty remains when interpreting the measured viral RNA signals and their spatiotemporal variation. The proliferation of measurements that are below a quantifiable threshold, usually during non-endemic periods, poses a further challenge to interpretation and time-series analysis of the data. Inspired by research in the use of a custom Kalman smoother model to estimate the true level of SARS-CoV-2 RNA concentrations in wastewater, we propose an alternative left-censored dynamic linear model. Cross-validation of both models alongside a simple moving average, using data from 286 sewage treatment works across England, allows for a comprehensive validation of the proposed approach. The presented dynamic linear model is more parsimonious, has a faster computational time and is represented by a more flexible modelling framework than the equivalent Kalman smoother. Furthermore we show how the use of wastewater data, transformed by such models, correlates more closely with regional case rate positivity as published by the Office for National Statistics (ONS) Coronavirus (COVID-19) Infection Survey. The modelled output is more robust and is therefore capable of better complementing traditional surveillance than untransformed data or a simple moving average, providing additional confidence and utility for public health decision making. La détection et la surveillance du SARS-CoV-2 dans les eaux usées ont été développées et réalisées à un rythme sans précédent, mais l'interprétation des mesures de concentrations en ARN viral, et de leurs variations spatio-temporelles, pose question. En particulier, l'importante proportion de mesures en deçà du seuil de quantification, généralement pendant les périodes non endémiques, constitue un défi pour l'analyse de ces séries temporelles. Inspirés par un travail de recherche ayant produit un lisseur de Kalman adapté pour estimer les concentrations réelles en ARN de SARS-CoV-2 dans les eaux usées à partir de ce type de données, nous proposons un nouveau modèle linéaire dynamique avec censure à gauche. Une validation croisée de ces lisseurs, ainsi que d'un simple lissage par moyenne glissante, sur des données provenant de 286 stations d'épuration couvrant l'Angleterre, valide de façon complète l'approche proposée. Le modèle présenté est plus parcimonieux, offre un cadre de modélisation plus flexible et nécessite un temps de calcul réduit par rapport au Lisseur de Kalman équivalent. Les données issues des eaux usées ainsi lissées sont en outre plus fortement corrélées avec le taux d'incidence régional produit par le bureau des statistiques nationales (ONS) Coronavirus Infection Survey. Elles se montrent plus robustes que les données brutes, ou lissées par simple moyenne glissante, et donc plus à même de compléter la surveillance traditionnelle, renforçant ainsi la confiance en l'épidémiologie fondée sur les eaux usées et son utilité pour la prise de décisions de santé publique.
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- 2023
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5. Parapneumonic effusions related to Streptococcus pneumoniae: serotype and disease severity trends from 2006 to 2018 in Bristol, UK
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Nick Maskell, Shamez Ladhani, Norman K Fry, Robert Challen, Adam Finn, Paul North, Catherine Hyams, David T Arnold, Zahin Amin-Chowdhury, Leon Danon, O Martin Williams, Philip Williams, Robyn Heath, David Hettle, Gabriella Ruffino, and Charli Grimes
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Medicine ,Diseases of the respiratory system ,RC705-779 - Abstract
Rationale Streptococcus pneumoniae epidemiology is changing in response to vaccination and some data suggest that empyema incidence is increasing. However, differences exist between the UK and US studies. We describe trends in the clinical phenotype of adult pneumococcal pleural infection, including simple parapneumonic effusions (SPE) in the pneumococcal conjugate vaccination (PCV) era.Objectives To determine whether there were differences in pneumococcal disease presentation and severity associated with pleural infection.Methods A retrospective cohort study, all adults ≥16 years admitted to three large UK hospitals, 2006–2018 with pneumococcal disease. 2477 invasive pneumococcal cases were identified: 459 SPE and 100 pleural infection cases. Medical records were reviewed for each clinical episode. Serotype data were obtained from the UK Health Security Agency national reference laboratory.Results Incidence increased over time, including non-PCV-serotype disease. PCV7-serotype disease declined following paediatric PCV7 introduction, but the effect of PCV13 was less apparent as disease caused by the additional six serotypes plateaued with serotypes 1 and 3 causing such parapneumonic effusions from 2011 onwards.Patients with pleural infection had a median survival 468 days (95% CI 340 to 590) vs 286 days (95% CI 274 to 335) in those with SPE. Pleural infection associated with frank pus had lower 90-day mortality than pleural infection without pus (0% vs 29%, p
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- 2023
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6. Voluntary risk mitigation behaviour can reduce impact of SARS-CoV-2: a real-time modelling study of the January 2022 Omicron wave in England
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Ellen Brooks-Pollock, Kate Northstone, Lorenzo Pellis, Francesca Scarabel, Amy Thomas, Emily Nixon, David A. Matthews, Vicky Bowyer, Maria Paz Garcia, Claire J. Steves, Nicholas J. Timpson, and Leon Danon
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SARS-CoV-2 ,Omicron variant ,Behaviour change ,Infectious disease modelling ,Scenario modelling ,policy ,Medicine - Abstract
Abstract Background Predicting the likely size of future SARS-CoV-2 waves is necessary for public health planning. In England, voluntary “plan B” mitigation measures were introduced in December 2021 including increased home working and face coverings in shops but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown. Methods We developed a rapid online survey of risk mitigation behaviours ahead of the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/COVID Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we predicted the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave. Results Over 95% of survey respondents (NALSPAC = 2686 and NTwins = 6155) reported some risk mitigation behaviours, with vaccination and using home testing kits reported most frequently. Less than half of those respondents reported that their behaviour was due to “plan B”. We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 12,000 and 46,000 cumulative deaths, depending on assumptions about severity and vaccine effectiveness. The actual number of deaths was 15,208 (26 November 2021–1 March 2022). We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%. Conclusions Predicting future infection burden is affected by uncertainty in disease severity and vaccine effectiveness estimates. In addition to biological uncertainty, we show that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant but that voluntary measures alone would be unlikely to completely control transmission.
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- 2023
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7. An analysis of 45 large-scale wastewater sites in England to estimate SARS-CoV-2 community prevalence
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Mario Morvan, Anna Lo Jacomo, Celia Souque, Matthew J. Wade, Till Hoffmann, Koen Pouwels, Chris Lilley, Andrew C. Singer, Jonathan Porter, Nicholas P. Evens, David I. Walker, Joshua T. Bunce, Andrew Engeli, Jasmine Grimsley, Kathleen M. O’Reilly, and Leon Danon
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Science - Abstract
Wastewater surveillance could provide a means of monitoring SARS-CoV-2 prevalence that does not rely on testing individuals. Here, the authors report results from England’s national wastewater surveillance program, use it to estimate prevalence, and compare estimates with those from population-based prevalence surveys.
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- 2022
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8. Effectiveness of BNT162b2 COVID-19 vaccination in prevention of hospitalisations and severe disease in adults with SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant between June 2021 and July 2022: A prospective test negative case–control studyResearch in context
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Anastasia Chatzilena, Catherine Hyams, Rob Challen, Robin Marlow, Jade King, David Adegbite, Jane Kinney, Madeleine Clout, Nick Maskell, Jennifer Oliver, Leon Danon, Adam Finn, Anna Morley, Amelia Langdon, Anabella Turner, Anya Mattocks, Bethany Osborne, Charli Grimes, Claire Mitchell, Emma Bridgeman, Emma Scott, Fiona Perkins, Francesca Bayley, Gabriella Ruffino, Gabriella Valentine, Grace Tilzey, Johanna Kellett Wright, Julia Brzezinska, Julie Cloake, Katarina Milutinovic, Kate Helliker, Katie Maughan, Kazminder Fox, Konstantina Minou, Lana Ward, Leah Fleming, Leigh Morrison, Lily Smart, Louise Wright, Lucy Grimwood, Maddalena Bellavia, Marianne Vasquez, Maria Garcia Gonzalez, Milo Jeenes-Flanagan, Natalie Chang, Niall Grace, Nicola Manning, Oliver Griffiths, Pip Croxford, Peter Sequenza, Rajeka Lazarus, Rhian Walters, Robyn Heath, Rupert Antico, Sandi Nammuni Arachchge, Seevakumar Suppiah, Taslima Mona, Tawassal Riaz, Vicki Mackay, Zandile Maseko, Zoe Taylor, Zsolt Friedrich, and Zsuzsa Szasz-Benczur
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COVID-19 ,SARS-CoV-2 ,Respiratory infection ,Vaccination ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Whilst other studies have reported the effectiveness of mRNA vaccination against hospitalisation, including emergency department or intensive care admission, few have assessed effectiveness against other more clinically robust indices of COVID-19 severity. Methods: A prospective single-centre test-negative design case–control study of adults hospitalised with COVID-19 disease or other acute respiratory disease between 1 June 2021 and 20 July 2022. We assessed VE (vaccine effectiveness) against hospitalisation, length of stay [LOS] >3 days, WHO COVID Score >5 and supplementary oxygen FiO2 (fraction inspired oxygen) >28%, conducting regression analyses controlling for age, gender, index of multiple deprivation, Charlson comorbidity index, time, and community infection prevalence. Findings: 935 controls and 546 cases were hospitalised during the Delta period, with 721 controls and 372 cases hospitalised during the Omicron study period. Two-dose BNT162b2 was associated with VE 82.5% [95% confidence interval 76.2%–87.2%] against hospitalisation following Delta infection, 63.3% [26.9–81.8%], 58.5% [24.8–77.3%], and 51.5% [16.7–72.1%] against LOS >3 days, WHO COVID Score >5, and requirement for FiO2 >28% respectively. Three-dose BNT162b2 protection against hospitalisation with Omicron infection was 30.9% [5.9–49.3%], with sensitivity analyses ranging from 28.8–72.6%. Protection against LOS >3 days, WHO COVID Score >5 and requirement for FiO2 >28% was 56.1% [20.6–76.5%], 58.8% [31.2–75.8%], and 41.5% [−0.4–66.3%], respectively. In the UK, BNT162b2 was prioritised for high-risk individuals and those aged >75 years. In the latter group we found a higher estimate of VE against hospitalisation of 47.2% [16.8–66.6%]. Interpretation: BNT162b2 vaccination results in risk reductions for hospitalisation and multiple patient outcomes following Delta and Omicron COVID-19 infection, particularly in older adults. BNT162b2 remains effective against severe SARS-CoV-2 disease. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.
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- 2023
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9. Severity of Omicron (B.1.1.529) and Delta (B.1.617.2) SARS-CoV-2 infection among hospitalised adults: A prospective cohort study in Bristol, United KingdomResearch in context
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Catherine Hyams, Robert Challen, Robin Marlow, Jennifer Nguyen, Elizabeth Begier, Jo Southern, Jade King, Anna Morley, Jane Kinney, Madeleine Clout, Jennifer Oliver, Sharon Gray, Gillian Ellsbury, Nick Maskell, Luis Jodar, Bradford Gessner, John McLaughlin, Leon Danon, Adam Finn, Amelia Langdon, Anabella Turner, Anya Mattocks, Bethany Osborne, Charli Grimes, Claire Mitchell, David Adegbite, Emma Bridgeman, Emma Scott, Fiona Perkins, Francesca Bayley, Gabriella Ruffino, Gabriella Valentine, Grace Tilzey, James Campling, Johanna Kellett Wright, Julia Brzezinska, Julie Cloake, Katarina Milutinovic, Kate Helliker, Katie Maughan, Kazminder Fox, Konstantina Minou, Lana Ward, Leah Fleming, Leigh Morrison, Lily Smart, Louise Wright, Lucy Grimwood, Maddalena Bellavia, Marianne Vasquez, Maria Garcia Gonzalez, Milo Jeenes-Flanagan, Natalie Chang, Niall Grace, Nicola Manning, Oliver Griffiths, Pip Croxford, Peter Sequenza, Rajeka Lazarus, Rhian Walters, Robyn Heath, Rupert Antico, Sandi Nammuni Arachchge, Seevakumar Suppiah, Taslima Mona, Tawassal Riaz, Vicki Mackay, Zandile Maseko, Zoe Taylor, Zsolt Friedrich, and Zsuzsa Szasz-Benczur
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COVID-19 ,SARS-CoV-2 ,Respiratory infection ,Vaccination ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity. Methods: A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection. Findings: Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 [Relative Risk (RR) = 0.42 (95%CI: 0.34–0.52), P 5 [RR = 0.33 (95%CI: 0.21–0.50), P 3 days [RR = 0.84 (95%CI: 0.76–0.92), P
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- 2023
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10. Seroprevalencia de SARS-CoV-2 en niños y adolescentes mexicanos en edad escolar
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Francisco Canto-Osorio, Dalia Stern, Carolina Pérez-Ferrer, Eduardo Arias-de la Garza, Leon Danon, Tonatiuh Barrientos-Gutiérrez, and Martín Lajous
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seroprevalencia ,sars-cov-2 ,niños ,adolescentes ,méxico ,Public aspects of medicine ,RA1-1270 - Abstract
Objetivo. Estimar la seroprevalencia de SARS-CoV-2 en población de edad escolar en México. Material y métodos. Se categorizaron a niños y adolescentes que participaron en la Encuesta Nacional de Salud y Nutrición 2020 sobre Covid-19 (Ensanut 2020 Covid-19) por edad escolar y nivel educativo. En participantes seropositivos, se identificó la proporción de infecciones asintomáticas. Se estimaron razones de prevalencia usando un modelo de regresión log-binomial. Resultados. La seroprevalencia en educación básica y media fue de 18.7% (IC95%: 14.9, 22.5) y 26.7% (IC95%: 22.1, 31.3), respectivamente. La infección asintomática fue más frecuente en educación básica (88.5% [IC95%: 80.5, 93.5]). Conclusiones. En población de educación básica la infección por SARS-CoV-2 es baja y usualmente asintomática.
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- 2021
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11. Incidence of community acquired lower respiratory tract disease in Bristol, UK during the COVID-19 pandemic: A prospective cohort study
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Catherine Hyams, Robert Challen, Elizabeth Begier, Jo Southern, Jade King, Anna Morley, Zsuzsa Szasz-Benczur, Maria Garcia Gonzalez, Jane Kinney, James Campling, Sharon Gray, Jennifer Oliver, Robin Hubler, Srinivas Valluri, Andrew Vyse, John M. McLaughlin, Gillian Ellsbury, Nick A. Maskell, Bradford D. Gessner, Leon Danon, Adam Finn, Amelia Langdon, Anabella Turner, Anya Mattocks, Bethany Osborne, Charli Grimes, Claire Mitchell, David Adegbite, Emma Bridgeman, Emma Scott, Fiona Perkins, Francesca Bayley, Gabriella Ruffino, Gabriella Valentine, Grace Tilzey, Johanna Kellett Wright, Julia Brzezinska, Julie Cloake, Katarina Milutinovic, Kate Helliker, Katie Maughan, Kazminder Fox, Konstantina Minou, Lana Ward, Leah Fleming, Leigh Morrison, Lily Smart, Louise Wright, Lucy Grimwood, Maddalena Bellavia, Madeleine Clout, Marianne Vasquez, Milo Jeenes-Flanagan, Natalie Chang, Niall Grace, Nicola Manning, Oliver Griffiths, Pip Croxford, Peter Sequenza, Rajeka Lazarus, Rhian Walters, Robin Marlow, Robyn Heath, Rupert Antico, Sandi Nammuni Arachchge, Seevakumar Suppiah, Taslima Mona, Tawassal Riaz, Vicki Mackay, Zandile Maseko, Zoe Taylor, and Zsolt Friedrich
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Pneumonia ,Lower respiratory tract infection ,Cardiac failure ,COVID-19 ,SARS-CoV-2 ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: The emergence of COVID-19 and public health measures implemented to reduce SARS-CoV-2 infections have both affected acute lower respiratory tract disease (aLRTD) epidemiology and incidence trends. The severity of COVID-19 and non-SARS-CoV-2 aLRTD during this period have not been compared in detail. Methods: We conducted a prospective cohort study of adults age ≥18 years admitted to either of two acute care hospitals in Bristol, UK, from August 2020 to November 2021. Patients were included if they presented with signs or symptoms of aLRTD (e.g., cough, pleurisy), or a clinical or radiological aLRTD diagnosis. Findings: 12,557 adult aLRTD hospitalisations occurred: 10,087 were associated with infection (pneumonia or non-pneumonic lower respiratory tract infection [NP-LRTI]), 2161 with no infective cause, with 306 providing a minimal surveillance dataset. Confirmed SARS-CoV-2 infection accounted for 32% (3178/10,087) of respiratory infections. Annual incidences of overall, COVID-19, and non- SARS-CoV-2 pneumonia were 714.1, 264.2, and 449.9, and NP-LRTI were 346.2, 43.8, and 302.4 per 100,000 adults, respectively. Weekly incidence trends in COVID-19 aLRTD showed large surges (median 6.5 [IQR 0.7–10.2] admissions per 100,000 adults per week), while other infective aLRTD events were more stable (median 14.3 [IQR 12.8–16.4] admissions per 100,000 adults per week) as were non-infective aLRTD events (median 4.4 [IQR 3.5–5.5] admissions per 100,000 adults per week). Interpretation: While COVID-19 disease was a large component of total aLRTD during this pandemic period, non- SARS-CoV-2 infection still caused the majority of respiratory infection hospitalisations. COVID-19 disease showed significant temporal fluctuations in frequency, which were less apparent in non-SARS-CoV-2 infection. Despite public health interventions to reduce respiratory infection, disease incidence remains high. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.
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- 2022
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12. High COVID-19 transmission potential associated with re-opening universities can be mitigated with layered interventions
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Ellen Brooks-Pollock, Hannah Christensen, Adam Trickey, Gibran Hemani, Emily Nixon, Amy C. Thomas, Katy Turner, Adam Finn, Matt Hickman, Caroline Relton, and Leon Danon
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Science - Abstract
Reopening of universities to students following COVID-19 restrictions risks increased transmission due to high numbers of social contacts and the potential for asymptomatic transmission. Here, the authors use a mathematical model with social contact data to estimate the impacts of reopening a typical non-campus based university in the UK.
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- 2021
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13. Contacts and behaviours of university students during the COVID-19 pandemic at the start of the 2020/2021 academic year
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Emily Nixon, Adam Trickey, Hannah Christensen, Adam Finn, Amy Thomas, Caroline Relton, Clara Montgomery, Gibran Hemani, Jane Metz, Josephine G. Walker, Katy Turner, Rachel Kwiatkowska, Sarah Sauchelli, Leon Danon, and Ellen Brooks-Pollock
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Medicine ,Science - Abstract
Abstract University students have unique living, learning and social arrangements which may have implications for infectious disease transmission. To address this data gap, we created CONQUEST (COroNavirus QUESTionnaire), a longitudinal online survey of contacts, behaviour, and COVID-19 symptoms for University of Bristol (UoB) staff/students. Here, we analyse results from 740 students providing 1261 unique records from the start of the 2020/2021 academic year (14/09/2020–01/11/2020), where COVID-19 outbreaks led to the self-isolation of all students in some halls of residences. Although most students reported lower daily contacts than in pre-COVID-19 studies, there was heterogeneity, with some reporting many (median = 2, mean = 6.1, standard deviation = 15.0; 8% had ≥ 20 contacts). Around 40% of students’ contacts were with individuals external to the university, indicating potential for transmission to non-students/staff. Only 61% of those reporting cardinal symptoms in the past week self-isolated, although 99% with a positive COVID-19 test during the 2 weeks before survey completion had self-isolated within the last week. Some students who self-isolated had many contacts (mean = 4.3, standard deviation = 10.6). Our results provide context to the COVID-19 outbreaks seen in universities and are available for modelling future outbreaks and informing policy.
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- 2021
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14. Vaccine escape in a heterogeneous population: insights for SARS-CoV-2 from a simple model
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Julia R. Gog, Edward M. Hill, Leon Danon, and Robin N. Thompson
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SARS-CoV-2 ,COVID-19 ,vaccine ,vaccine escape ,heterogeneous population ,policy ,Science - Abstract
As a countermeasure to the SARS-CoV-2 pandemic, there has been swift development and clinical trial assessment of candidate vaccines, with subsequent deployment as part of mass vaccination campaigns. However, the SARS-CoV-2 virus has demonstrated the ability to mutate and develop variants, which can modify epidemiological properties and potentially also the effectiveness of vaccines. The widespread deployment of highly effective vaccines may rapidly exert selection pressure on the SARS-CoV-2 virus directed towards mutations that escape the vaccine-induced immune response. This is particularly concerning while infection is widespread. By developing and analysing a mathematical model of two population groupings with differing vulnerability and contact rates, we explore the impact of the deployment of vaccines among the population on the reproduction ratio, cases, disease abundance and vaccine escape pressure. The results from this model illustrate two insights: (i) vaccination aimed at reducing prevalence could be more effective at reducing disease than directly vaccinating the vulnerable; (ii) the highest risk for vaccine escape can occur at intermediate levels of vaccination. This work demonstrates a key principle: the careful targeting of vaccines towards particular population groups could reduce disease as much as possible while limiting the risk of vaccine escape.
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- 2021
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15. Detecting behavioural changes in human movement to inform the spatial scale of interventions against COVID-19.
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Hamish Gibbs, Emily Nightingale, Yang Liu, James Cheshire, Leon Danon, Liam Smeeth, Carl A B Pearson, Chris Grundy, LSHTM CMMID COVID-19 working group, Adam J Kucharski, and Rosalind M Eggo
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Biology (General) ,QH301-705.5 - Abstract
On March 23 2020, the UK enacted an intensive, nationwide lockdown to mitigate transmission of COVID-19. As restrictions began to ease, more localized interventions were used to target resurgences in transmission. Understanding the spatial scale of networks of human interaction, and how these networks change over time, is critical to targeting interventions at the most at-risk areas without unnecessarily restricting areas at low risk of resurgence. We use detailed human mobility data aggregated from Facebook users to determine how the spatially-explicit network of movements changed before and during the lockdown period, in response to the easing of restrictions, and to the introduction of locally-targeted interventions. We also apply community detection techniques to the weighted, directed network of movements to identify geographically-explicit movement communities and measure the evolution of these community structures through time. We found that the mobility network became more sparse and the number of mobility communities decreased under the national lockdown, a change that disproportionately affected long distance connections central to the mobility network. We also found that the community structure of areas in which locally-targeted interventions were implemented following epidemic resurgence did not show reorganization of community structure but did show small decreases in indicators of travel outside of local areas. We propose that communities detected using Facebook or other mobility data be used to assess the impact of spatially-targeted restrictions and may inform policymakers about the spatial extent of human movement patterns in the UK. These data are available in near real-time, allowing quantification of changes in the distribution of the population across the UK, as well as changes in travel patterns to inform our understanding of the impact of geographically-targeted interventions.
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- 2021
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16. Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework
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Katharine J Looker, Katherine M E Turner, Fergus Hamilton, Louis MacGregor, Catherine Hyams, Ross D Booton, Lucy Vass, Philip D Bright, Irasha Harding, Rajeka Lazarus, Daniel Lawson, Leon Danon, Adrian Pratt, Richard Wood, and Ellen Brooks-Pollock
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Medicine - Abstract
Objectives To develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case.Design Open-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.Setting SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.Participants Publicly available data on patients with COVID-19.Primary and secondary outcome measures The expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction (‘R’) number over time.Results SW model projections indicate that, as of 11 May 2020 (when ‘lockdown’ measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7).Conclusions The developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and—as open-source software—is portable to healthcare systems in other geographies.
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- 2021
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17. Correction: A flexible method for optimising sharing of healthcare resources and demand in the context of the COVID-19 pandemic.
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Lucas Lacasa, Robert Challen, Ellen Brooks-Pollock, and Leon Danon
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0241027.].
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- 2021
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18. A model of tuberculosis clustering in low incidence countries reveals more transmission in the United Kingdom than the Netherlands between 2010 and 2015.
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Ellen Brooks-Pollock, Leon Danon, Hester Korthals Altes, Jennifer A Davidson, Andrew M T Pollock, Dick van Soolingen, Colin Campbell, and Maeve K Lalor
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Biology (General) ,QH301-705.5 - Abstract
Tuberculosis (TB) remains a public health threat in low TB incidence countries, through a combination of reactivated disease and onward transmission. Using surveillance data from the United Kingdom (UK) and the Netherlands (NL), we demonstrate a simple and predictable relationship between the probability of observing a cluster and its size (the number of cases with a single genotype). We demonstrate that the full range of observed cluster sizes can be described using a modified branching process model with the individual reproduction number following a Poisson lognormal distribution. We estimate that, on average, between 2010 and 2015, a TB case generated 0.41 (95% CrI 0.30,0.60) secondary cases in the UK, and 0.24 (0.14,0.48) secondary cases in the NL. A majority of cases did not generate any secondary cases. Recent transmission accounted for 39% (26%,60%) of UK cases and 23%(13%,37%) of NL cases. We predict that reducing UK transmission rates to those observed in the NL would result in 538(266,818) fewer cases annually in the UK. In conclusion, while TB in low incidence countries is strongly associated with reactivated infections, we demonstrate that recent transmission remains sufficient to warrant policies aimed at limiting local TB spread.
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- 2020
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19. A flexible method for optimising sharing of healthcare resources and demand in the context of the COVID-19 pandemic.
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Lucas Lacasa, Robert Challen, Ellen Brooks-Pollock, and Leon Danon
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Medicine ,Science - Abstract
As the number of cases of COVID-19 continues to grow, local health services are at risk of being overwhelmed with patients requiring intensive care. We develop and implement an algorithm to provide optimal re-routing strategies to either transfer patients requiring Intensive Care Units (ICU) or ventilators, constrained by feasibility of transfer. We validate our approach with realistic data from the United Kingdom and Spain. In the UK, we consider the National Health Service at the level of trusts and define a 4-regular geometric graph which indicates the four nearest neighbours of any given trust. In Spain we coarse-grain the healthcare system at the level of autonomous communities, and extract similar contact networks. Through random search optimisation we identify the best load sharing strategy, where the cost function to minimise is based on the total number of ICU units above capacity. Our framework is general and flexible allowing for additional criteria, alternative cost functions, and can be extended to other resources beyond ICU units or ventilators. Assuming a uniform ICU demand, we show that it is possible to enable access to ICU for up to 1000 additional cases in the UK in a single step of the algorithm. Under a more realistic and heterogeneous demand, our method is able to balance about 600 beds per step in the Spanish system only using local sharing, and over 1300 using countrywide sharing, potentially saving a large percentage of these lives that would otherwise not have access to ICU.
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- 2020
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20. Seasonally timed treatment programs for Ascaris lumbricoides to increase impact-An investigation using mathematical models.
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Emma L Davis, Leon Danon, Joaquín M Prada, Sharmini A Gunawardena, James E Truscott, Johnny Vlaminck, Roy M Anderson, Bruno Levecke, Eric R Morgan, and T Deirdre Hollingsworth
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA) could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period) between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings.
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- 2018
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21. Pneumococcal Serotypes Colonise the Nasopharynx in Children at Different Densities.
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Fernanda Rodrigues, Leon Danon, Begonia Morales-Aza, Paulina Sikora, Valtyr Thors, Muriel Ferreira, Katherine Gould, Jason Hinds, and Adam Finn
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Medicine ,Science - Abstract
Prevalence of pneumococcal serotypes in carriage and disease has been described but absolute serotype colonisation densities have not been reported. 515 paediatric nasal swab DNA extracts were subjected to lytA qPCR and molecular serotyping by microarray. Absolute serotype densities were derived from total pneumococcal density (qPCR cycle threshold and standard curve) and relative abundance (microarray) and varied widely. Compared to all serotype densities observed, the strongest evidence of differences was seen for serotypes 21 and 35B (higher) and 3, 38 and non-typeables (lower) (p
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- 2016
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22. Strategies for controlling non-transmissible infection outbreaks using a large human movement data set.
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Penelope A Hancock, Yasmin Rehman, Ian M Hall, Obaghe Edeghere, Leon Danon, Thomas A House, and Matthew J Keeling
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Biology (General) ,QH301-705.5 - Abstract
Prediction and control of the spread of infectious disease in human populations benefits greatly from our growing capacity to quantify human movement behavior. Here we develop a mathematical model for non-transmissible infections contracted from a localized environmental source, informed by a detailed description of movement patterns of the population of Great Britain. The model is applied to outbreaks of Legionnaires' disease, a potentially life-threatening form of pneumonia caused by the bacteria Legionella pneumophilia. We use case-report data from three recent outbreaks that have occurred in Great Britain where the source has already been identified by public health agencies. We first demonstrate that the amount of individual-level heterogeneity incorporated in the movement data greatly influences our ability to predict the source location. The most accurate predictions were obtained using reported travel histories to describe movements of infected individuals, but using detailed simulation models to estimate movement patterns offers an effective fast alternative. Secondly, once the source is identified, we show that our model can be used to accurately determine the population likely to have been exposed to the pathogen, and hence predict the residential locations of infected individuals. The results give rise to an effective control strategy that can be implemented rapidly in response to an outbreak.
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- 2014
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23. Filling the Knowledge Gap: Measuring HIV Prevalence and Risk Factors among Men Who Have Sex with Men and Female Sex Workers in Tripoli, Libya.
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Joseph J Valadez, Sima Berendes, Caroline Jeffery, Joanna Thomson, Hussain Ben Othman, Leon Danon, Abdullah A Turki, Rabea Saffialden, and Lusine Mirzoyan
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Medicine ,Science - Abstract
Publications on Libya's HIV epidemic mostly examined the victims of the tragic nosocomial HIV outbreak in the 1990s and the related dispute about the detention of foreign medical workers. The dispute resolution in 2003 included an agreement with the European Union on humanitarian cooperation and the development of Libya's first National HIV Strategy. As part of this we conducted Libya's first bio-behavioural survey among men having sex with men (MSM) and female sex workers (FSW).Using respondent-driven sampling, we conducted a cross-sectional study to estimate the prevalence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and related risk factors among 227 MSM and 69 FSW in Tripoli (FSW recruitment ended prematurely due to the political events in 2011).For MSM we estimated an HIV prevalence of 3.1%, HBV prevalence of 2.9%, and HCV prevalence of 7.3%, and for FSW an HIV prevalence of 15.7%, HBV prevalence of 0%, and HCV prevalence of 5.2%. We detected high levels of risk behaviours, poor HIV-related knowledge, high stigma and lack of prevention programmes. These results must be interpreted in the context of the political situation which prohibited reaching an ideal sample size for FSW.There is urgent need to implement an effective National HIV Strategy informed by the results of this research. The risk of transmission within different risk groups and to the general population may be high given the recent military events that led to increased violence, migration, and the disruption of essential HIV-related services.
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- 2013
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24. Networks and the Epidemiology of Infectious Disease
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Leon Danon, Ashley P. Ford, Thomas House, Chris P. Jewell, Matt J. Keeling, Gareth O. Roberts, Joshua V. Ross, and Matthew C. Vernon
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Infectious and parasitic diseases ,RC109-216 - Abstract
The science of networks has revolutionised research into the dynamics of interacting elements. It could be argued that epidemiology in particular has embraced the potential of network theory more than any other discipline. Here we review the growing body of research concerning the spread of infectious diseases on networks, focusing on the interplay between network theory and epidemiology. The review is split into four main sections, which examine: the types of network relevant to epidemiology; the multitude of ways these networks can be characterised; the statistical methods that can be applied to infer the epidemiological parameters on a realised network; and finally simulation and analytical methods to determine epidemic dynamics on a given network. Given the breadth of areas covered and the ever-expanding number of publications, a comprehensive review of all work is impossible. Instead, we provide a personalised overview into the areas of network epidemiology that have seen the greatest progress in recent years or have the greatest potential to provide novel insights. As such, considerable importance is placed on analytical approaches and statistical methods which are both rapidly expanding fields. Throughout this review we restrict our attention to epidemiological issues.
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- 2011
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25. Student behavior during a school closure caused by pandemic influenza A/H1N1.
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Joel C Miller, Leon Danon, Justin J O'Hagan, Edward Goldstein, Martin Lajous, and Marc Lipsitch
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Medicine ,Science - Abstract
Many schools were temporarily closed in response to outbreaks of the recently emerged pandemic influenza A/H1N1 virus. The effectiveness of closing schools to reduce transmission depends largely on student/family behavior during the closure. We sought to improve our understanding of these behaviors.To characterize this behavior, we surveyed students in grades 9-12 and parents of students in grades 5-8 about student activities during a week long closure of a school during the first months after the disease emerged. We found significant interaction with the community and other students-though less interaction with other students than during school-with the level of interaction increasing with grade.Our results are useful for the future design of social distancing policies and to improving the ability of modeling studies to accurately predict their impact.
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- 2010
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26. Use of cumulative incidence of novel influenza A/H1N1 in foreign travelers to estimate lower bounds on cumulative incidence in Mexico.
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Marc Lipsitch, Martin Lajous, Justin J O'Hagan, Ted Cohen, Joel C Miller, Edward Goldstein, Leon Danon, Jacco Wallinga, Steven Riley, Scott F Dowell, Carrie Reed, and Meg McCarron
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Medicine ,Science - Abstract
An accurate estimate of the total number of cases and severity of illness of an emerging infectious disease is required both to define the burden of the epidemic and to determine the severity of disease. When a novel pathogen first appears, affected individuals with severe symptoms are more likely to be diagnosed. Accordingly, the total number of cases will be underestimated and disease severity overestimated. This problem is manifest in the current epidemic of novel influenza A/H1N1.We used a simple approach to leverage measures of incident influenza A/H1N1 among a relatively small and well observed group of US, UK, Spanish and Canadian travelers who had visited Mexico to estimate the incidence among a much larger and less well surveyed population of Mexican residents. We estimate that a minimum of 113,000 to 375,000 cases of novel influenza A/H1N1 have occurred in Mexicans during the month of April, 2009. Such an estimate serves as a lower bound because it does not account for underreporting of cases in travelers or for nonrandom mixing between Mexican residents and visitors, which together could increase the estimates by more than an order of magnitude.We find that the number of cases in Mexican residents may exceed the number of confirmed cases by two to three orders of magnitude. While the extent of disease spread is greater than previously appreciated, our estimate suggests that severe disease is uncommon since the total number of cases is likely to be much larger than those of confirmed cases.
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- 2009
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27. Mobile Messaging as Surveillance Tool during Pandemic (H1N1) 2009, Mexico
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Martín Lajous, Leon Danon, Ruy López-Ridaura, Christina M. Astley, Joel C. Miller, Scott F. Dowell, Justin J. O’Hagan, Edward Goldstein, and Marc Lipsitch
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Influenza ,cell phone ,surveillance ,mobile messaging ,survey ,viruses ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 2010
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28. Dynamic Network Anomaly Modeling of Cell-Phone Call Detail Records for Infectious Disease Surveillance.
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Carl Yang 0001, Hongwen Song, Mingyue Tang, Leon Danon, and Ymir Vigfusson
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- 2022
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29. MetaWards: A flexible metapopulation framework for modelling disease spread.
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Christopher J. Woods, Lester O. Hedges, Christopher Edsall, Ellen Brooks-Pollock, Christopher Parton-Fenton, Trevelyan J. McKinley, Matt J. Keeling, and Leon Danon
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- 2022
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30. Trends in serotype distribution and disease severity in adults hospitalised withStreptococcus pneumoniaeinfection in Bristol and Bath: a retrospective cohort study, 2006-2022
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Catherine Hyams, Robert Challen, David Hettle, Zahin Amin-Chowdhury, Charli Grimes, Gabriella Ruffino, Rauri Conway, Robyn Heath, Paul North, Adam Malin, Nick A Maskell, Philip Williams, O. Martin Williams, Shamez N Ladhani, Leon Danon, and Adam Finn
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BackgroundPaediatric pneumococcal conjugate vaccination (PCV) has reduced adult PCV-serotype disease: PCV7 has greater indirect effects than PCV13. Ongoing surveillance is required to evaluate current vaccine usage and inform future vaccine deployment, particularly with respiratory infection epidemiology changing following SARS-CoV-2 emergence.Methods and FindingsA retrospective cohort study, all adults ≥16 years admitted to three UK hospitals, 2006-2022, with pneumococcal disease. Medical records were reviewed for each clinical episode and serotype data were obtained from the UK Health Security Agency national reference laboratory.We identified 1,501 (40.3%) cases of invasive pneumococcal disease (IPD) with known serotype, 134 (3.6%) IPD cases without serotype data, and 2,084 (56.0%) non-IPD cases, which are typically missed in national surveillance. Disease incidence increased progressively from 2006-2020, followed by a sudden decline after COVID-19 emergence and then a gradual increase to pre-pandemic levels.Paediatric PCV7 introduction reduced adult PCV7 serotype IPD from 29.4% [24.1–35.4] of IPD in 2006-09 to 7.0% [3.7–12.7] in 2021-22. PCV13 introduction also decreased adult vaccine serotype IPD, but considerable residual adult disease remains, causing 34.3% [28.6–40.4] of IPD in 2006-09 and 21.7% [15.5–29.6] 9 in 2021-22, respectively. Serotype replacement diminished the benefits of PCV introduction: PCV20-13 and non-PCV serotypes represented 27.0% [21.9–32.9] and 9.3% [6.3–13.5] of disease in 2006-2009, and 39.5% [31.5–48.2] and 31.8% [24.4–40.2] in 2021-2022, respectively.Serotype shifts have resulted in increasing disease caused by serotype 3 and 8, and the re-emergence of serotype 19F and 19A. These serotype shifts occurred as clinical disease severity changed, and whilst the COVID-19 pandemic disrupted disease severity trends, these have now largely reverted to previous trajectories. Patient age trended upwards and although CURB65 severity decreased there were increased ICU admission rates. Overall, inpatient mortality decreased and hospitalisation duration remained stable.ConclusionsAfter 17 years of PCV use, residual pneumococcal disease due to the vaccine serotypes among hospitalised adults remains. The sharp decline in pneumococcal disease during the COVID-19 pandemic has now reversed, with increasing cases due to vaccine serotypes, especially serotype 3. Around 68.2% of cases in 2022 were potentially covered by the recently licensed 20-valent PCV.
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- 2023
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31. Meta-analysis of the severe acute respiratory syndrome coronavirus 2 serial intervals and the impact of parameter uncertainty on the coronavirus disease 2019 reproduction number
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Robert Challen, Ellen Brooks-Pollock, Krasimira Tsaneva-Atanasova, and Leon Danon
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Statistics and Probability ,Health Information Management ,SARS-CoV-2 ,Epidemiology ,Reproduction ,Uncertainty ,COVID-19 ,Humans ,Disease Outbreaks - Abstract
The serial interval of an infectious disease, commonly interpreted as the time between the onset of symptoms in sequentially infected individuals within a chain of transmission, is a key epidemiological quantity involved in estimating the reproduction number. The serial interval is closely related to other key quantities, including the incubation period, the generation interval (the time between sequential infections), and time delays between infection and the observations associated with monitoring an outbreak such as confirmed cases, hospital admissions, and deaths. Estimates of these quantities are often based on small data sets from early contact tracing and are subject to considerable uncertainty, which is especially true for early coronavirus disease 2019 data. In this paper, we estimate these key quantities in the context of coronavirus disease 2019 for the UK, including a meta-analysis of early estimates of the serial interval. We estimate distributions for the serial interval with a mean of 5.9 (95% CI 5.2; 6.7) and SD 4.1 (95% CI 3.8; 4.7) days (empirical distribution), the generation interval with a mean of 4.9 (95% CI 4.2; 5.5) and SD 2.0 (95% CI 0.5; 3.2) days (fitted gamma distribution), and the incubation period with a mean 5.2 (95% CI 4.9; 5.5) and SD 5.5 (95% CI 5.1; 5.9) days (fitted log-normal distribution). We quantify the impact of the uncertainty surrounding the serial interval, generation interval, incubation period, and time delays, on the subsequent estimation of the reproduction number, when pragmatic and more formal approaches are taken. These estimates place empirical bounds on the estimates of most relevant model parameters and are expected to contribute to modeling coronavirus disease 2019 transmission.
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- 2021
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32. Seroprevalencia de SARS-CoV-2 en niños y adolescentes mexicanos en edad escolar
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Carolina Pérez-Ferrer, Leon Danon, Dalia Stern, Francisco Canto-Osorio, Eduardo Arias de la Garza, Tonatiuh Barrientos-Gutiérrez, and Martin Lajous
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Gynecology ,National health ,medicine.medical_specialty ,Secondary education ,School age child ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Public Health, Environmental and Occupational Health ,Usually asymptomatic ,Asymptomatic ,Medicine ,Seroprevalence ,medicine.symptom ,business - Abstract
espanolObjetivo. Estimar la seroprevalencia de SARS-CoV-2 en po-blacion de edad escolar en Mexico. Material y metodos. Se categorizaron a ninos y adolescentes que participaron en la Encuesta Nacional de Salud y Nutricion 2020 sobre Covid-19 (Ensanut 2020 Covid-19) por edad escolar y nivel educativo. En participantes seropositivos, se identifico la pro-porcion de infecciones asintomaticas. Se estimaron razones de prevalencia usando un modelo de regresion log-binomial. Resultados. La seroprevalencia en educacion basica y media fue de 18.7% (IC95%: 14.9, 22.5) y 26.7% (IC95%: 22.1, 31.3), respectivamente. La infeccion asintomatica fue mas frecuente en educacion basica (88.5% [IC95%: 80.5, 93.5]). Conclusiones. En poblacion de educacion basica la infeccion por SARS-CoV-2 es baja y usualmente asintomatica. EnglishObjective. To estimate the seroprevalence of SARS-CoV-2 in school aged children in Mexico. Materials and methods. We categorized children and adolescents who participated in 2020 National Health and Nutrition Survey on Covid-19 according to school age and educational level. In seropositive participants, we identified the proportion of as-ymptomatic infections. We estimated prevalence ratios using a log-binomial regression model. Results. Seroprevalence of SARS-CoV-2 for primary and secondary education were 18.7% (95%IC: 14.9, 22.5) and 26.7% (95%IC: 22.1, 31.3), re-spectively. Asymptomatic infection was more frequent among primary school children (88.5% [95%IC: 80.5, 93.5]). Conclu-sions. In primary schoolchildren seroprevalence for SARS-CoV-2 was low and infections were usually asymptomatic.
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- 2021
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33. Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001:A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults
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Rajeka Lazarus, Christian Taucher, Claire Brown, Irena Čorbic Ramljak, Leon Danon, Katrin Dubischar, Christopher J.A. Duncan, Susanne Eder-Lingelbach, Saul N. Faust, Christopher Green, Karishma Gokani, Romana Hochreiter, Johanna Kellett Wright, Dowan Kwon, Alexander Middleditch, Alasdair P.S. Munro, Kush Naker, Florentina Penciu, David Price, Benedicte Querton, Tawassal Riaz, Amy Ross-Russell, Amada Sanchez-Gonzalez, Hayley Wardle, Sarah Warren, and Adam Finn
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Adult ,Microbiology (medical) ,COVID-19 Vaccines ,SARS-CoV-2 ,Immunization, Passive ,COVID-19 ,Covid19 ,Neutralizing antibody ,Antibodies, Viral ,Antibodies, Neutralizing ,CpG 1018 ,S protein binding IgG antibody ,Whole-virus vaccine ,Coronavirus ,Immunogenicity, Vaccine ,Infectious Diseases ,Double-Blind Method ,RBD-binding IgG antibody ,Humans ,Adjuvanted vaccine ,COVID-19 Serotherapy ,Inactivated vaccine - Abstract
ObjectivesWe aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001.MethodsWe conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017.ResultsBetween December 16, 2020, and June 3, 2021, 153 healthy adults aged 18–55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively.ConclusionsVLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.
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- 2022
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34. Severity of Omicron (B.1.1.529) and Delta (B.1.1.617.2) SARS-CoV-2 infection among hospitalised adults: a prospective cohort study
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Catherine Hyams, Robert Challen, Robin Marlow, Jennifer Nguyen, Elizabeth Begier, Jo Southern, Jade King, Anna Morley, Jane Kinney, Madeleine Clout, Jennifer Oliver, Gillian Ellsbury, Nick Maskell, Luis Jodar, Bradford Gessner, John McLaughlin, Leon Danon, and Adam Finn
- Abstract
Limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 variant infections, and to what extent patient-factors, including vaccination and pre-existing disease, affect variant-dependent disease severity. This prospective cohort study of all adults (≥18 years of age) hospitalised at acute care hospitals in Bristol, UK assessed disease severity using 3 different measures: FiO2 >28%, World Health Organization (WHO) outcome score >5, and hospital length of stay (LOS) >3 days following admission for Omicron or Delta variant infection. Independent of other variables, including vaccination, Omicron variant infection was associated with a statistically lower severity compared to Delta; risk reductions were 58%, 67%, and 16% for FiO2, WHO score, and LOS, respectively. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden following admission.
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- 2022
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35. Local Search with Congestion in Complex Communication Networks.
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Alex Arenas, Leon Danon, Albert Díaz-Guilera, and Roger Guimerà
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- 2004
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36. Severity of Omicron (B.1.1.529) and Delta (B.1.617.2) SARS-CoV-2 infection among hospitalised adults: a prospective cohort study in Bristol, United Kingdom
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Catherine Hyams, Robert Challen, Robin Marlow, Jennifer Nguyen, Elizabeth Begier, Jo Southern, Jade King, Anna Morley, Jane Kinney, Madeleine Clout, Jennifer Oliver, Sharon Gray, Gillian Ellsbury, Nick Maskell, Luis Jodar, Bradford Gessner, John McLaughlin, Leon Danon, and Adam Finn
- Abstract
BackgroundThere is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity.MethodsA prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2>28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection.FindingsIndependent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2[Relative Risk (RR)=0·42 (95%CI: 0·34-0·52),P5 [RR=0·33 (95%CI: 0·21-0·50),P3 days [RR=0·84 (95%CI: 0·76-0·92),PInterpretationWe provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease.FundingAvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.RESEARCH IN CONTEXTEvidence before this studyThe burden of COVID-19 on hospital services is determined by the prevalence and severity of SARS-CoV-2 variants, and modified by individual factors such as age, frailty and vaccination status. Real world data suggest that vaccine effectiveness is lower and may wane faster over time against symptomatic disease with Omicron (B.1.1.529) than with Delta (B.1.617.2) SARS-CoV-2 variant. However, numbers of hospitalisations as a case proportion during the Omicron wave have been considerably lower than previous waves. Several reports have compared the risk of hospitalisation or severe disease based on SARS-CoV-2 variant, some suggesting that Omicron is probably less severe than Delta in vaccinated and unvaccinated individuals.Added value of this studyThis study provides robust data assessing the relative severity of Delta and Omicron SARS-CoV-2 variants in patients admitted to hospital, including the first analysis assessing risk for any positive pressure ventilatory support, as well as risk of supplementary oxygen requirement and extended hospital admission, that may guide resource planning in hospitals. We found evidence that infection with Omicron was associated with a milder clinical course following hospital admission than that caused by Delta and that vaccination was independently associated with lower in-hospital disease severity using these three separate severity measures. Specifically, compared to Delta, Omicron-related hospitalizations were 58%, 67%, and 16% less likely to require high flow oxygen >28% FiO2, positive pressure ventilatory support or more critical care, and to have a hospital stay lasting more than three days, respectively.This study reports the considerable morbidity resulting from Omicron infection, with 18% of Omicron admissions requiring oxygen supplementation FiO2>28%, 6% requiring positive pressure ventilation, 62% needing hospitalization ≥four days, and 4% in-hospital mortality. In determining the reduced requirement of increased oxygen requirement and total positive pressure requirement, including non-invasive ventilation, this analysis should contribute to future hospital care and service planning assessments.Implications of all the available evidenceThe risk of severe outcomes following SARS-CoV-2 infection is substantially lower for Omicron than for Delta, with greater reductions for more severe disease outcomes. Significant variation in risk occurs with age and vaccination status, with older and unvaccinated individuals remaining at particular risk of adverse outcome. These results highlight the importance of maintaining high levels of vaccine coverage in patient groups at risk of severe disease.The impact of lower severity Omicron-related hospitalization must be balanced against increased transmissibility and overall higher numbers of infections with this variant and there remains a substantial patient and public health burden. The increased admission rate of older patients with Omicron counteracts some of the benefit arising from less severe disease. Despite the risk reduction in high level oxygen supplementation requirement and high dependency care with Omicron compared to earlier variants at the individual level, healthcare systems could still be overwhelmed.
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- 2022
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37. Upper respiratory tract colonization withStreptococcus pneumoniaein adults
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Maria Cristina de Cunto Brandileone, Daniela M. Ferreira, Jose A Suaya, Samir K. Saha, Katherine L. O'Brien, Raul E Isturiz, Raquel Sá-Leão, Anne L. Wyllie, Luis Jodar, Bradford D Gessner, Krzysztof Trzciński, Leon Danon, Adriano Arguedas, Chiara Azzari, Stephen I. Pelton, Laura L. Hammitt, and Daniel M. Weinberger
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0301 basic medicine ,Pharmacology ,business.industry ,Immunology ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Carriage ,Drug Discovery ,Streptococcus pneumoniae ,medicine ,Molecular Medicine ,Colonization ,030212 general & internal medicine ,Respiratory system ,business ,Disease burden ,Respiratory tract - Abstract
Most of the current evidence regarding pneumococcal upper respiratory colonization in adults suggests that despite high disease burden, carriage prevalence is low. Contemporary studies on adult pne...
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- 2020
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38. Factors influencing digital review of pathology test results in an inpatient setting: a cross-sectional study
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Luke Gompels, Krasimira Tsaneva-Atanasova, Mark Dayer, Thomas L Edwards, Leon Danon, Martin Pitt, and Robert Challen
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Quality management ,AcademicSubjects/SCI01060 ,Cross-sectional study ,test result follow-up ,Health Informatics ,Research and Applications ,Delayed diagnosis ,quality improvement ,laboratory informatics ,03 medical and health sciences ,0302 clinical medicine ,data quality ,Medicine ,030212 general & internal medicine ,business.industry ,030503 health policy & services ,Inpatient setting ,Phlebotomy ,medicine.disease ,Test (assessment) ,clinical workflow ,Workflow ,Data quality ,Medical emergency ,AcademicSubjects/SCI01530 ,AcademicSubjects/MED00010 ,0305 other medical science ,business - Abstract
Background Delay or failure to view test results in a hospital setting can lead to delayed diagnosis, risk of patient harm, and represents inefficiency. Factors influencing this were investigated to identify how timeliness and completeness of test review could be improved through an evidence-based redesign of the use of clinical test review software. Methods A cross-section of all abnormal hematology and biochemistry results which were published on a digital test review platform over a 3-year period were investigated. The time it took for clinicians to view these results, and the results that were not viewed within 30 days, were analyzed relative to time of the week, the detailed type of test, and an indicator of patient record data quality. Results The majority of results were viewed within 90 min, and 93.9% of these results viewed on the digital platform within 30 days. There was significant variation in results review throughout the week, shown to be due to an interplay between technical and clinical workflow factors. Routine results were less likely to be reviewed, as were those with patient record data quality issues. Conclusion The evidence suggests that test result review would be improved by stream-lining access to the result platform, differentiating between urgent and routine results, improving handover of responsibility for result review, and improving search for temporary patient records. Altering the timing of phlebotomy rounds and a review of the appropriateness of routine test requests at the weekend may also improve result review rates.
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- 2020
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39. Parapneumonic effusions related toStreptococcus pneumoniae: serotype and disease severity trends from 2006 to 2018 in Bristol, UK
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Catherine Hyams, David T Arnold, Robyn Heath, Zahin Amin-Chowdhury, David Hettle, Gabriella Ruffino, Paul North, Charli Grimes, Norman K Fry, Philip Williams, Robert Challen, Leon Danon, O Martin Williams, Shamez Ladhani, Adam Finn, and Nick A Maskell
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Pulmonary and Respiratory Medicine - Abstract
RationaleStreptococcus pneumoniaeepidemiology is changing in response to vaccination and some data suggest empyema incidence is increasing. However, differences exist between UK and USA studies. We describe trends in the clinical phenotype of adult pneumococcal pleural infection, including simple parapneumonic effusions (SPE) in the pneumococcal conjugate vaccination (PCV) era.ObjectivesTo determine whether there were differences in pneumococcal disease presentation and severity associated with pleural infection.MethodsA retrospective cohort study, all adults ≥16 years admitted to three large UK hospitals, 2006-2018 with pneumococcal disease. 2477 invasive pneumococcal cases were identified: 459 SPE and 100 pleural infection cases. Medical records were reviewed for each clinical episode. Serotype data were obtained from the UK Health Security Agency national reference laboratory.ResultsIncidence increased over time, including non-PCV-serotype disease. PCV7-serotype disease declined following paediatric PCV7 introduction, but the effect of PCV13 was less apparent as disease caused by the additional six serotypes plateaued with serotypes 1 and 3 causing such parapneumonic effusions from 2011 onwards.Patients with pleural infection had a median survival 468 days (95% CI 340-590), versus 286 days (95% CI 274-335) in those with SPE. Pleural infection associated with frank pus had lower 90-day mortality than pleural infection without pus (0% versus 29%,PP=0.049).ConclusionsPneumococcal infection continues to cause severe disease despite the introduction of PCVs. The predominance of serotype 1 and 3 in this adult UK cohort is in keeping with previous studies in paediatric and non-UK studies. Rising non-PCV serotype disease and limited impact of PCV13 on cases caused by serotypes 1 and 3 offset the reductions in adult pneumococcal parapneumonic effusion disease burden observed following introduction of the childhood PCV7 programme.KEY MESSAGESWhat is already known on this topicThe epidemiology of pneumococcal infection is changing in both adults and children following pneumococcal conjugate vaccine (PCV) introduction, as a result of direct and indirect vaccine effects. Other studies have reported that serotypes 1 and 3 disproportionately cause pneumococcal pleural disease; however, the clinical phenotype of parapneumonic effusions associated with pneumococcal infection in adults following PCV introduction is not well described.What this study addsIn this study which presents the largest cohort of patients with a single-organism pleural infection, we demonstrate an increasing incidence of parapneumonic effusions related toStreptococcus pneumoniaein adults, attributable to serotype 1 and 3 disease, despite the introduction of PCV13 in the UK childhood vaccination programme. Interestingly, our data suggest that pneumococcal pleural infection is associated with improved survival up to one-year compared to patients with pneumococcal simple parapneumonic effusions.How this study might affect research, practice or policyCareful assessment of the need for specialist respiratory and thoracic surgical intervention in the context of increasing incidence of adult parapneumonic effusions related toStreptococcus pneumoniaewill be required, in addition to ongoing monitoring of the effect on serotype distribution and clinical phenotype of current and future vaccines against pneumococcus.
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- 2022
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40. Impact of voluntary risk-mitigation behaviour on transmission of the Omicron SARS-CoV-2 variant in England
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Ellen Brooks-Pollock, Kate Northstone, Lorenzo Pellis, Francesca Scarabel, Amy Thomas, Emily Nixon, David A. Matthews, Vicky Bowyer, Maria Paz Garcia, Claire J. Steves, Nicholas J. Timpson, and Leon Danon
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BackgroundThe Omicron variant of SARS-CoV-2 infection poses substantial challenges to public health. In England, “plan B” mitigation measures were introduced in December 2021 including increased home working and face coverings in shops, but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown.MethodsWe developed a rapid online survey of risk mitigation behaviours during the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/Covid Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we describe the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave.ResultsOver 95% of survey respondents (NALSPAC=2,686 and NTwins=6,155) reported some risk mitigation behaviours, with vaccination and using home testing kits reported most frequently. Less than half of those respondents reported that their behaviour was due to “plan B”. We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 15,000 and 46,000 cumulative deaths, depending on assumptions about vaccine effectiveness. We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%.ConclusionsWe conclude that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant, but that voluntary measures alone would be unlikely to completely control transmission.
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- 2022
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41. Effectiveness of BNT162b2 COVID-19 Vaccination in Prevention of Hospitalisations and Severe Disease in Adults with Delta (B.1.617.2) and Omicron (B.1.1.529) Variant SARS-CoV-2 Infection: A Prospective Test Negative Case-Control Study
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Anastasia Chatzilena, Catherine Hyams, Robert Challen, Robin Marlow, Jade King, David Adegbite, Jane Kinney, Madeleine Clout Clout, Nick A. Maskell, Jennifer Oliver, Leon Danon, and Adam Finn
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- 2022
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42. Parapneumonic Effusions Related to Streptococcus Pneumoniae: Serotype and Disease Severity Trends
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Catherine Hyams, David T. Arnold, Robyn Heath, Zahin Amin-Chowdhury, David Hettle, Gabriella Ruffino, Paul North, Charli Grimes, Norman Fry, Philip Williams, Leon Danon, O. Martin Williams, Shamez Ladhani, Adam Finn, and Nick Maskell
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- 2022
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43. Incidence of Community Acquired Lower Respiratory Tract Disease in Bristol, UK During the COVID-19 Pandemic
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Catherine Hyams, Robert Challen, Elizabeth Begier, Jo Southern, Jade King, Anna Morley, Zsuzsa Szasz-Benczur, Maria Garcia Gonzalez, Jane Kinney, James Campling, Sharon Gray, Jennifer Oliver, Robin Hubler, Srinivas R. Valluri, Andrew Vyse, John M. McLaughlin, Gillian Ellsbury, Nick Maskell, Bradford Gessner, Leon Danon, and Adam Finn
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
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44. Impact of SARS-CoV-2 Infective Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) on Clinical Outcomes in a Prospective Cohort Study of Hospitalised Adults
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Catherine Hyams, George Qian, George Nava, Robert Challen, Elizabeth Begier, Jo Southern, Maria Laheurta, Jennifer L. Nguyen, Jade King, Anna Morley, Madeleine Clout Clout, Nick A. Maskell, Luis Jodar, Jennifer Oliver, Gillian Ellsbury, John M. McLaughlin, Bradford Gessner, Adam Finn, Leon Danon, James Dodd, and The Avon CAP Research Group
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
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45. Short-term Projections based on Early Omicron Variant Dynamics in England
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Matt J. Keeling, Ellen Brooks-Pollock, Rob Challen, Leon Danon, Louise Dyson, Julia R. Gog, Laura Guzmán Rincón, Edward M. Hill, Lorenzo Pellis, Jonathan M. Read, and Michael J. Tildesley
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Throughout the ongoing COVID-19 pandemic, the worldwide transmission and replication of SARS-COV-2, the causative agent of COVID-19 disease, has resulted in the opportunity for multiple mutations to occur that may alter the virus transmission characteristics, the effectiveness of vaccines and the severity of disease upon infection. The Omicron variant (B.1.1.529) was first reported to the WHO by South Africa on 24 November 2021 and was declared a variant of concern by the WHO on 26 November 2021. The variant was first detected in the UK on 27 November 2021 and has since been reported in a number of countries globally where it is frequently associated with rapid increase in cases. Here we present analyses of UK data showing the earliest signatures of the Omicron variant and mathematical modelling that uses the UK data to simulate the potential impact of this variant in the UK. In order to account for the uncertainty in transmission advantage, vaccine escape and severity at the time of writing, we carry out a sensitivity analysis to assess the impact of these variant characteristics on future risk.
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- 2021
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46. Impacts of vaccination and asymptomatic testing on SARS-CoV-2 transmission dynamics in a university setting
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Ellen Brooks Pollock, Rachel Kwiatkowska, Gibran Hemani, Amy Thomas, Adam Trickey, Josephine G. Walker, Daniel A Stocks, Leon Danon, Antoine M G Barreaux, Hannah Christensen, Emily Nixon, David Ellis, and Caroline L Relton
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Pediatrics ,medicine.medical_specialty ,Student population ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Psychological intervention ,Outbreak ,Asymptomatic ,law.invention ,Vaccination ,Transmission (mechanics) ,law ,medicine ,Cumulative incidence ,medicine.symptom ,business - Abstract
We investigate the impact of vaccination and asymptomatic testing uptake on SARS-CoV-2 transmission in a university student population using a stochastic compartmental model. We find that the magnitude and timing of outbreaks is highly variable depending on the transmissibility of the most dominant strain of SARS CoV-2 and under different vaccine uptake levels and efficacies. When delta is the dominant strain, low level interventions (no asymptomatic testing, 30% vaccinated with a vaccine that is 80% effective at reducing infection) lead to 53-71% of students become infected during the first term. Asymptomatic testing is most useful when vaccine uptake is low: when 30% of students are vaccinated, 90% uptake of asymptomatic testing leads to almost half the case numbers. With high interventions (90% using asymptomatic testing, 90% vaccinated) cumulative incidence is 7-9%, with around 80% of these cases estimated to be asymptomatic. However, under emergence of a new variant that is at least twice as transmissible as delta and with the vaccine efficacy against infection reduced to 55%, large outbreaks are likely in universities, even with very high (90%) uptake of vaccination and 100% uptake of asymptomatic testing. If vaccine efficacy against infection against this new variant is higher (70%), then outbreaks can be mitigated if there is least 50% uptake of asymptomatic testing additional to 90% uptake of vaccination. Our findings suggest that effective vaccination is critical for controlling SARS-CoV-2 transmission in university settings with asymptomatic testing ranging from additionally useful to critical, depending on effectiveness and uptake of vaccination. Other measures may be necessary to control outbreaks under the emergence of a more transmissible variant with vaccine escape.
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- 2021
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47. Community Structure in Jazz.
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Pablo M. Gleiser and Leon Danon
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- 2003
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48. University students and staff able to maintain low daily contact numbers during various COVID-19 guideline periods
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Sarah Sauchelli, Adam Trickey, Rachel Kwiatkowska, Josephine G. Walker, Adam Finn, Gibran Hemani, Clara Montgomery, Leon Danon, Katy Turner, Amy Thomas, Hannah Christensen, Ellen Brooks-Pollock, Caroline L Relton, Emily Nixon, and Jane Metz
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2019-20 coronavirus outbreak ,Medical education ,Original Paper ,contacts ,Coronavirus disease 2019 (COVID-19) ,Epidemiology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Social distance ,coronavirus ,Covid19 ,Guideline ,behaviour ,Coronavirus ,Infectious Diseases ,statistics ,UK ,Psychology - Abstract
UK universities re-opened in September 2020, amidst the coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November; however, outbreaks among university students occurred. We aimed to measure the University of Bristol staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020–03/07/2020), relaxed guidance period (04/07/2020–13/09/2020), ‘rule-of-six’ period (14/09/2020–04/11/2020) and the second lockdown (05/11/2020–25/11/2020). In total, 722 staff (4199 responses) and 738 students (1906 responses) were included in the study. For staff, daily contacts were higher in the relaxed guidance and ‘rule-of-six’ periods than the post-first lockdown and second lockdown. Mean student contacts dropped between the ‘rule-of-six’ and second lockdown periods. For both staff and students, the proportion meeting with groups larger than six dropped between the ‘rule-of-six’ period and the second lockdown period, although was higher for students than for staff. Our results suggest university staff and students responded to national guidance by altering their social contacts. Most contacts during the second lockdown were household contacts. The response in staff and students was similar, suggesting that students can adhere to social distancing guidance while at university. The number of contacts recorded for both staff and students were much lower than those recorded by previous surveys in the UK conducted before the COVID-19 pandemic.
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- 2021
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49. Vaccine escape in a heterogeneous population: insights for SARS-CoV-2 from a simple model
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Edward M. Hill, Julia R. Gog, Robin N Thompson, Leon Danon, Gog, Julia R. [0000-0003-1240-7214], Hill, Edward M. [0000-0002-2992-2004], Danon, Leon [0000-0002-7076-1871], Thompson, Robin N. [0000-0001-8545-5212], Apollo - University of Cambridge Repository, Gog, Julia R [0000-0003-1240-7214], Hill, Edward M [0000-0002-2992-2004], Thompson, Robin N [0000-0001-8545-5212], and Gog, Julia [0000-0003-1240-7214]
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0301 basic medicine ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Population ,Vulnerability ,Disease ,Biology ,vaccine escape ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,vaccine ,Pandemic ,Vaccine escape ,030212 general & internal medicine ,education ,education.field_of_study ,Multidisciplinary ,SARS-CoV-2 ,COVID-19 ,Science, society and policy ,heterogeneous population ,QR ,Vaccination ,030104 developmental biology ,RA ,policy - Abstract
As a countermeasure to the SARS-CoV-2 pandemic, there has been swift development and clinical trial assessment of candidate vaccines, with subsequent deployment as part of mass vaccination campaigns. However, the SARS-CoV-2 virus has demonstrated the ability to mutate and develop variants, which can modify epidemiological properties and potentially also the effectiveness of vaccines. The widespread deployment of highly effective vaccines may rapidly exert selection pressure on the SARS-CoV-2 virus directed towards mutations that escape the vaccine-induced immune response. This is particularly concerning while infection is widespread. By developing and analysing a mathematical model of two population groupings with differing vulnerability and contact rates, we explore the impact of the deployment of vaccines among the population on the reproduction ratio, cases, disease abundance and vaccine escape pressure. The results from this model illustrate two insights: (i) vaccination aimed at reducing prevalence could be more effective at reducing disease than directly vaccinating the vulnerable; (ii) the highest risk for vaccine escape can occur at intermediate levels of vaccination. This work demonstrates a key principle: the careful targeting of vaccines towards particular population groups could reduce disease as much as possible while limiting the risk of vaccine escape.
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- 2021
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50. The population attributable fraction of cases due to gatherings and groups with relevance to COVID-19 mitigation strategies
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Ellen Brooks-Pollock, Graham F. Medley, Jonathan M. Read, Thomas House, Matthew James Keeling, and Leon Danon
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medicine.medical_specialty ,gatherings ,Coronavirus disease 2019 (COVID-19) ,population attributable fraction (PAF) ,Physical Distancing ,Population ,Basic Reproduction Number ,HM ,General Biochemistry, Genetics and Molecular Biology ,Disease Outbreaks ,Pandemic ,Epidemiology ,medicine ,Humans ,education ,Pandemics ,Research Articles ,education.field_of_study ,SARS-CoV-2 ,business.industry ,COVID-19 ,Outbreak ,Articles ,Confidence interval ,Attributable risk ,General Agricultural and Biological Sciences ,business ,Basic reproduction number ,RA ,Demography - Abstract
Many countries have banned groups and gatherings as part of their response to the pandemic caused by the coronavirus, SARS-CoV-2. Although there are outbreak reports involving mass gatherings, the contribution to overall transmission is unknown. We used data from a survey of social contact behaviour that specifically asked about contact with groups to estimate the population attributable fraction (PAF) due to groups as the relative change in the basic reproduction number when groups are prevented. Groups of 50+ individuals accounted for 0.5% of reported contact events, and we estimate that the PAF due to groups of 50+ people is 5.4% (95% confidence interval 1.4%, 11.5%). The PAF due to groups of 20+ people is 18.9% (12.7%, 25.7%) and the PAF due to groups of 10+ is 25.2% (19.4%, 31.4%). Under normal circumstances with pre-COVID-19 contact patterns, large groups of individuals have a relatively small epidemiological impact; small- and medium-sized groups between 10 and 50 people have a larger impact on an epidemic. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
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- 2021
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