46 results on '"Parag, Kris V."'
Search Results
2. Genomic Epidemiology of Early SARS-CoV-2 Transmission Dynamics, Gujarat, India
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Raghwani, Jayna, Plessis, Louis du, McCrone, John T., Hill, Sarah C., Parag, Kris V., Theze, Julien, Kumar, Dinesh, Puvar, Apurva, Pandit, Ramesh, Pybus, Oliver G., Fournie, Guillaume, Joshi, Madhvi, and Joshi, Chaitanya
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Gujarat, India (State) -- Health aspects ,Epidemics -- Distribution -- Risk factors -- India ,Disease transmission -- Distribution -- Risk factors ,Company distribution practices ,Health - Abstract
Global genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has provided key insights into virus dissemination and evolution at local, national, and international scales. Detailed analysis of the [...]
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- 2022
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3. Impact of spatiotemporal heterogeneity in COVID-19 disease surveillance on epidemiological parameters and case growth rates
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Inward, Rhys P.D., Jackson, Felix, Dasgupta, Abhishek, Lee, Graham, Battle, Anya Lindström, Parag, Kris V., and Kraemer, Moritz U.G.
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- 2022
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4. Using multiple sampling strategies to estimate SARS-CoV-2 epidemiological parameters from genomic sequencing data
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Inward, Rhys P. D., Parag, Kris V., and Faria, Nuno R.
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- 2022
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5. Tracking the emergence of disparities in the subnational spread of COVID-19 in Brazil using an online application for real-time data visualisation: A longitudinal analysis
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Mee, Paul, Alexander, Neal, Mayaud, Philippe, González, Felipe de Jesus Colón, Abbott, Sam, Santos, Andreza Aruska de Souza, Acosta, André Luís, Parag, Kris V., Pereira, Rafael H.M., Prete, Carlos A., Jr, Sabino, Ester C., Faria, Nuno R., and Brady, Oliver J
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- 2022
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6. Adaptive Estimation for Epidemic Renewal and Phylogenetic Skyline Models
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Parag, Kris V. and Donnelly, Christl A.
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- 2020
7. Key questions for modelling COVID-19 exit strategies
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Thompson, Robin N., Hollingsworth, T. Déirdre, Isham, Valerie, Arribas-Bel, Daniel, Ashby, Ben, Britton, Tom, Challenor, Peter, Chappell, Lauren H. K., Clapham, Hannah, Cunniffe, Nik J., Dawid, A. Philip, Donnelly, Christl A., Eggo, Rosalind M., Funk, Sebastian, Gilbert, Nigel, Glendinning, Paul, Gog, Julia R., Hart, William S., Heesterbeek, Hans, House, Thomas, Keeling, Matt, Kiss, István Z., Kretzschmar, Mirjam E., Lloyd, Alun L., McBryde, Emma S., McCaw, James M., McKinley, Trevelyan J., Miller, Joel C., Morris, Martina, O’Neill, Philip D., Parag, Kris V., Pearson, Carl A. B., Pellis, Lorenzo, Pulliam, Juliet R. C., Ross, Joshua V., Tomba, Gianpaolo Scalia, Silverman, Bernard W., Struchiner, Claudio J., Tildesley, Michael J., Trapman, Pieter, Webb, Cerian R., Mollison, Denis, and Restif, Olivier
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- 2020
8. Database of epidemic trends and control measures during the first wave of COVID-19 in mainland China
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Fu, Han, Wang, Haowei, Xi, Xiaoyue, Boonyasiri, Adhiratha, Wang, Yuanrong, Hinsley, Wes, Fraser, Keith J., McCabe, Ruth, Olivera Mesa, Daniela, Skarp, Janetta, Ledda, Alice, Dewé, Tamsin, Dighe, Amy, Winskill, Peter, van Elsland, Sabine L., Ainslie, Kylie E.C., Baguelin, Marc, Bhatt, Samir, Boyd, Olivia, Brazeau, Nicholas F., Cattarino, Lorenzo, Charles, Giovanni, Coupland, Helen, Cucunuba, Zulma M., Cuomo-Dannenburg, Gina, Donnelly, Christl A., Dorigatti, Ilaria, Eales, Oliver D., FitzJohn, Richard G., Flaxman, Seth, Gaythorpe, Katy A.M., Ghani, Azra C., Green, William D., Hamlet, Arran, Hauck, Katharina, Haw, David J., Jeffrey, Benjamin, Laydon, Daniel J., Lees, John A., Mellan, Thomas, Mishra, Swapnil, Nedjati-Gilani, Gemma, Nouvellet, Pierre, Okell, Lucy, Parag, Kris V., Ragonnet-Cronin, Manon, Riley, Steven, Schmit, Nora, Thompson, Hayley A., Unwin, H.Juliette T., Verity, Robert, Vollmer, Michaela A.C., Volz, Erik, Walker, Patrick G.T., Walters, Caroline E., Watson, Oliver J., Whittaker, Charles, Whittles, Lilith K., Imai, Natsuko, Bhatia, Sangeeta, and Ferguson, Neil M.
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- 2021
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9. Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study
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Hogan, Alexandra B, Jewell, Britta L, Sherrard-Smith, Ellie, Vesga, Juan F, Watson, Oliver J, Whittaker, Charles, Hamlet, Arran, Smith, Jennifer A, Winskill, Peter, Verity, Robert, Baguelin, Marc, Lees, John A, Whittles, Lilith K, Ainslie, Kylie E C, Bhatt, Samir, Boonyasiri, Adhiratha, Brazeau, Nicholas F, Cattarino, Lorenzo, Cooper, Laura V, Coupland, Helen, Cuomo-Dannenburg, Gina, Dighe, Amy, Djaafara, Bimandra A, Donnelly, Christl A, Eaton, Jeff W, van Elsland, Sabine L, FitzJohn, Richard G, Fu, Han, Gaythorpe, Katy A M, Green, William, Haw, David J, Hayes, Sarah, Hinsley, Wes, Imai, Natsuko, Laydon, Daniel J, Mangal, Tara D, Mellan, Thomas A, Mishra, Swapnil, Nedjati-Gilani, Gemma, Parag, Kris V, Thompson, Hayley A, Unwin, H Juliette T, Vollmer, Michaela A C, Walters, Caroline E, Wang, Haowei, Wang, Yuanrong, Xi, Xiaoyue, Ferguson, Neil M, Okell, Lucy C, Churcher, Thomas S, Arinaminpathy, Nimalan, Ghani, Azra C, Walker, Patrick G T, and Hallett, Timothy B
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- 2020
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10. Robust Design for Coalescent Model Inference
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Parag, Kris V. and Pybus, Oliver G.
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- 2019
11. Comparative micro-epidemiology of pathogenic avian influenza virus outbreaks in a wild bird population
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Hill, Sarah C., Hansen, Rowena, Watson, Samantha, Coward, Vivien, Russell, Christine, Cooper, Jayne, Essen, Steve, Everest, Holly, Parag, Kris V., Fiddaman, Steven, Reid, Scott, Lewis, Nicola, Brookes, Sharon M., Smith, Adrian L., Sheldon, Ben, Perrins, Christopher M., Brown, Ian H., and Pybus, Oliver G.
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- 2019
12. Reduction in mobility and COVID-19 transmission
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Nouvellet, Pierre, Bhatia, Sangeeta, Cori, Anne, Ainslie, Kylie E. C., Baguelin, Marc, Bhatt, Samir, Boonyasiri, Adhiratha, Brazeau, Nicholas F., Cattarino, Lorenzo, Cooper, Laura V., Coupland, Helen, Cucunuba, Zulma M., Cuomo-Dannenburg, Gina, Dighe, Amy, Djaafara, Bimandra A., Dorigatti, Ilaria, Eales, Oliver D., van Elsland, Sabine L., Nascimento, Fabricia F., FitzJohn, Richard G., Gaythorpe, Katy A. M., Geidelberg, Lily, Green, William D., Hamlet, Arran, Hauck, Katharina, Hinsley, Wes, Imai, Natsuko, Jeffrey, Benjamin, Knock, Edward, Laydon, Daniel J., Lees, John A., Mangal, Tara, Mellan, Thomas A., Nedjati-Gilani, Gemma, Parag, Kris V., Pons-Salort, Margarita, Ragonnet-Cronin, Manon, Riley, Steven, Unwin, H. Juliette T., Verity, Robert, Vollmer, Michaela A. C., Volz, Erik, Walker, Patrick G. T., Walters, Caroline E., Wang, Haowei, Watson, Oliver J., Whittaker, Charles, Whittles, Lilith K., Xi, Xiaoyue, Ferguson, Neil M., and Donnelly, Christl A.
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- 2021
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13. Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil
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de Souza, William Marciel, Buss, Lewis Fletcher, Candido, Darlan da Silva, Carrera, Jean-Paul, Li, Sabrina, Zarebski, Alexander E., Pereira, Rafael Henrique Moraes, Prete, Jr, Carlos A., de Souza-Santos, Andreza Aruska, Parag, Kris V., Belotti, Maria Carolina T. D., Vincenti-Gonzalez, Maria F., Messina, Janey, da Silva Sales, Flavia Cristina, Andrade, Pamela dos Santos, Nascimento, Vítor Heloiz, Ghilardi, Fabio, Abade, Leandro, Gutierrez, Bernardo, Kraemer, Moritz U. G., Braga, Carlos K. V., Aguiar, Renato Santana, Alexander, Neal, Mayaud, Philippe, Brady, Oliver J., Marcilio, Izabel, Gouveia, Nelson, Li, Guangdi, Tami, Adriana, de Oliveira, Silvano Barbosa, Porto, Victor Bertollo Gomes, Ganem, Fabiana, de Almeida, Walquiria Aparecida Ferreira, Fantinato, Francieli Fontana Sutile Tardetti, Macário, Eduardo Marques, de Oliveira, Wanderson Kleber, Nogueira, Mauricio L., Pybus, Oliver G., Wu, Chieh-Hsi, Croda, Julio, Sabino, Ester C., and Faria, Nuno Rodrigues
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- 2020
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14. State-level tracking of COVID-19 in the United States
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Unwin, H. Juliette T., Mishra, Swapnil, Bradley, Valerie C., Gandy, Axel, Mellan, Thomas A., Coupland, Helen, Ish-Horowicz, Jonathan, Vollmer, Michaela A. C., Whittaker, Charles, Filippi, Sarah L., Xi, Xiaoyue, Monod, Mélodie, Ratmann, Oliver, Hutchinson, Michael, Valka, Fabian, Zhu, Harrison, Hawryluk, Iwona, Milton, Philip, Ainslie, Kylie E. C., Baguelin, Marc, Boonyasiri, Adhiratha, Brazeau, Nick F., Cattarino, Lorenzo, Cucunuba, Zulma, Cuomo-Dannenburg, Gina, Dorigatti, Ilaria, Eales, Oliver D., Eaton, Jeffrey W., van Elsland, Sabine L., FitzJohn, Richard G., Gaythorpe, Katy A. M., Green, William, Hinsley, Wes, Jeffrey, Benjamin, Knock, Edward, Laydon, Daniel J., Lees, John, Nedjati-Gilani, Gemma, Nouvellet, Pierre, Okell, Lucy, Parag, Kris V., Siveroni, Igor, Thompson, Hayley A., Walker, Patrick, Walters, Caroline E., Watson, Oliver J., Whittles, Lilith K., Ghani, Azra C., Ferguson, Neil M., Riley, Steven, Donnelly, Christl A., Bhatt, Samir, and Flaxman, Seth
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- 2020
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15. Retrospective evaluation of real-time estimates of global COVID-19 transmission trends and mortality forecasts.
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Bhatia, Sangeeta, Parag, Kris V., Wardle, Jack, Nash, Rebecca K., Imai, Natsuko, Elsland, Sabine L. Van, Lassmann, Britta, Brownstein, John S., Desai, Angel, Herringer, Mark, Sewalk, Kara, Loeb, Sarah Claire, Ramatowski, John, Cuomo-Dannenburg, Gina, Jauneikaite, Elita, Unwin, H. Juliette T., Riley, Steven, Ferguson, Neil, Donnelly, Christl A., and Cori, Anne
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DEATH forecasting , *COVID-19 pandemic , *COVID-19 , *SARS-CoV-2 - Abstract
Since 8th March 2020 up to the time of writing, we have been producing near real-time weekly estimates of SARS-CoV-2 transmissibility and forecasts of deaths due to COVID-19 for all countries with evidence of sustained transmission, shared online. We also developed a novel heuristic to combine weekly estimates of transmissibility to produce forecasts over a 4-week horizon. Here we present a retrospective evaluation of the forecasts produced between 8th March to 29th November 2020 for 81 countries. We evaluated the robustness of the forecasts produced in real-time using relative error, coverage probability, and comparisons with null models. During the 39-week period covered by this study, both the short- and medium-term forecasts captured well the epidemic trajectory across different waves of COVID-19 infections with small relative errors over the forecast horizon. The model was well calibrated with 56.3% and 45.6% of the observations lying in the 50% Credible Interval in 1-week and 4-week ahead forecasts respectively. The retrospective evaluation of our models shows that simple transmission models calibrated using routine disease surveillance data can reliably capture the epidemic trajectory in multiple countries. The medium-term forecasts can be used in conjunction with the short-term forecasts of COVID-19 mortality as a useful planning tool as countries continue to relax public health measures. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Angular reproduction numbers improve estimates of transmissibility when disease generation times are misspecified or time-varying.
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Parag, Kris V., Cowling, Benjamin J., and Lambert, Ben C.
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REPRODUCTION , *BRANCHING processes , *TIME measurements , *INFECTIOUS disease transmission , *EPIDEMICS , *COMMUNICABLE diseases - Abstract
We introduce the angular reproduction number Ω, which measures time-varying changes in epidemic transmissibility resulting from variations in both the effective reproduction number R, and generation time distribution w. Predominant approaches for tracking pathogen spread infer either R or the epidemic growth rate r. However, R is biased by mismatches between the assumed and true w, while r is difficult to interpret in terms of the individual-level branching process underpinning transmission. R and r may also disagree on the relative transmissibility of epidemics or variants (i.e. rA > rB does not imply RA > RB for variants A and B). We find that Ω responds meaningfully to mismatches and time-variations in w while mostly maintaining the interpretability of R. We prove that Ω > 1 implies R > 1 and that Ω agrees with r on the relative transmissibility of pathogens. Estimating Ω is no more difficult than inferring R, uses existing software, and requires no generation time measurements. These advantages come at the expense of selecting one free parameter. We propose Ω as complementary statistic to R and r that improves transmissibility estimates when w is misspecified or time-varying and better reflects the impact of interventions, when those interventions concurrently change R and w or alter the relative risk of co-circulating pathogens. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Seasonal dynamics of the wild rodent faecal virome.
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Raghwani, Jayna, Faust, Christina L., François, Sarah, Nguyen, Dung, Marsh, Kirsty, Raulo, Aura, Hill, Sarah C., Parag, Kris V., Simmonds, Peter, Knowles, Sarah C. L., and Pybus, Oliver G.
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TEMPERATE forests ,SEASONS ,RODENTS ,VIRAL shedding ,INFECTIOUS disease transmission - Abstract
Viral discovery studies in wild animals often rely on cross‐sectional surveys at a single time point. As a result, our understanding of the temporal stability of wild animal viromes remains poorly resolved. While studies of single host–virus systems indicate that host and environmental factors influence seasonal virus transmission dynamics, comparable insights for whole viral communities in multiple hosts are lacking. Utilizing noninvasive faecal samples from a long‐term wild rodent study, we characterized viral communities of three common European rodent species (Apodemus sylvaticus, A. flavicollis and Myodes glareolus) living in temperate woodland over a single year. Our findings indicate that a substantial fraction of the rodent virome is seasonally transient and associated with vertebrate or bacteria hosts. Further analyses of one of the most common virus families, Picornaviridae, show pronounced temporal changes in viral richness and evenness, which were associated with concurrent and up to ~3‐month lags in host density, ambient temperature, rainfall and humidity, suggesting complex feedbacks from the host and environmental factors on virus transmission and shedding in seasonal habitats. Overall, this study emphasizes the importance of understanding the seasonal dynamics of wild animal viromes in order to better predict and mitigate zoonotic risks. see also the Perspective by Wei‐shan Chang and Michelle Wille [ABSTRACT FROM AUTHOR]
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- 2023
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18. Risk averse reproduction numbers improve resurgence detection.
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Parag, Kris V. and Obolski, Uri
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INFECTIOUS disease transmission , *REPRODUCTION , *REAL-time computing , *COMMUNICABLE diseases , *SOCIODEMOGRAPHIC factors - Abstract
The effective reproduction number R is a prominent statistic for inferring the transmissibility of infectious diseases and effectiveness of interventions. R purportedly provides an easy-to-interpret threshold for deducing whether an epidemic will grow (R>1) or decline (R<1). We posit that this interpretation can be misleading and statistically overconfident when applied to infections accumulated from groups featuring heterogeneous dynamics. These groups may be delineated by geography, infectiousness or sociodemographic factors. In these settings, R implicitly weights the dynamics of the groups by their number of circulating infections. We find that this weighting can cause delayed detection of outbreak resurgence and premature signalling of epidemic control because it underrepresents the risks from highly transmissible groups. Applying E-optimal experimental design theory, we develop a weighting algorithm to minimise these issues, yielding the risk averse reproduction number E. Using simulations, analytic approaches and real-world COVID-19 data stratified at the city and district level, we show that E meaningfully summarises transmission dynamics across groups, balancing bias from the averaging underlying R with variance from directly using local group estimates. An E>1generates timely resurgence signals (upweighting risky groups), while an E<1ensures local outbreaks are under control. We propose E as an alternative to R for informing policy and assessing transmissibility at large scales (e.g., state-wide or nationally), where R is commonly computed but well-mixed or homogeneity assumptions break down. Author summary: How can we meaningfully summarise the transmission dynamics of an infectious disease? This question, although fundamental to epidemiology and crucial for informing the design and implementation of interventions (e.g., quarantines), is still not resolved. Current practice is to estimate the effective reproduction number R, which counts the average number of new infections generated per past infection, at large scales (e.g., nationally). An estimated R>1 signals epidemic growth. While R is easily interpreted and computed in real time, it averages infections across diverse locations or socio-demographic groups that likely possess different transmission dynamics. We prove that this averaging in R reduces sensitivity to resurgence, making R>1 slow to reflect realistic epidemic growth. This delay can substantially misinform policymakers and impede interventions. We apply optimal design theory to derive the risk averse reproduction number E as an alternative summary of diverse transmission dynamics. Using mathematical arguments, simulations and empirical COVID-19 datasets, we show that E>1 is an improved threshold for resurgence, providing timelier signals for informing policy or interventions and better uncertainty quantification. Further, E maintains the computability and interpretability of R. We propose E as meaningful statistic at large scales, where the averaging within R likely misrepresents the diversity of transmission dynamics. [ABSTRACT FROM AUTHOR]
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- 2023
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19. Accounting for the Potential of Overdispersion in Estimation of the Time-varying Reproduction Number.
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Ho, Faith, Parag, Kris V., Adam, Dillon C., Lau, Eric H. Y., Cowling, Benjamin J., and Tsang, Tim K.
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Background: The time-varying reproduction number, R
t , is commonly used to monitor the transmissibility of an infectious disease during an epidemic, but standard methods for estimating Rt seldom account for the impact of overdispersion on transmission. Methods: We developed a negative binomial framework to estimate Rt and a time-varying dispersion parameter (kt ). We applied the framework to COVID-19 incidence data in Hong Kong in 2020 and 2021. We conducted a simulation study to compare the performance of our model with the conventional Poisson-based approach. Results: Our framework estimated an Rt peaking around 4 (95% credible interval = 3.13, 4.30), similar to that from the Poisson approach but with a better model fit. Our approach further estimated kt <0.5 at the start of both waves, indicating appreciable heterogeneity in transmission. We also found that kt decreased sharply to around 0.4 when a large cluster of infections occurred. Conclusions: Our proposed approach can contribute to the estimation of Rt and monitoring of the time-varying dispersion parameters to quantify the role of superspreading. [ABSTRACT FROM AUTHOR]- Published
- 2023
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20. Authors' reply to the discussion of 'Are epidemic growth rates more informative than reproduction numbers?' by Parag et al. in Session 1 of the Royal Statistical Society's Special Topic Meeting on COVID‐19 transmission: 9 June 2021.
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Parag, Kris V., Thompson, Robin N., and Donnelly, Christl A.
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SARS Epidemic, 2002-2003 ,EPIDEMICS - Abstract
One R estimate may not provide all the important information needed to understand a varied transmission landscape, but in that case one r estimate may not either. As to whether the difference between Dr Dagpunar's derivation and the approximation often used has a substantial effect in practice, all we can say is that the effect is likely limited for the simulated examples we considered in our contribution (which use generation times based on those estimated for Ebola virus or SARS-CoV-2). Authors' reply to the discussion of 'Are epidemic growth rates more informative than reproduction numbers?. [Extracted from the article]
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- 2022
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21. Are epidemic growth rates more informative than reproduction numbers?
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Parag, Kris V., Thompson, Robin N., and Donnelly, Christl A.
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EPIDEMICS ,HEALTH policy ,REPRODUCTION - Abstract
Summary statistics, often derived from simplified models of epidemic spread, inform public health policy in real time. The instantaneous reproduction number, Rt, is predominant among these statistics, measuring the average ability of an infection to multiply. However, Rt encodes no temporal information and is sensitive to modelling assumptions. Consequently, some have proposed the epidemic growth rate, rt, that is, the rate of change of the log‐transformed case incidence, as a more temporally meaningful and model‐agnostic policy guide. We examine this assertion, identifying if and when estimates of rt are more informative than those of Rt. We assess their relative strengths both for learning about pathogen transmission mechanisms and for guiding public health interventions in real time. [ABSTRACT FROM AUTHOR]
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- 2022
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22. Fundamental limits on inferring epidemic resurgence in real time using effective reproduction numbers.
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Parag, Kris V. and Donnelly, Christl A.
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HEALTH policy , *DEMOGRAPHIC characteristics , *EMERGING infectious diseases , *FALSE alarms , *EPIDEMICS - Abstract
We find that epidemic resurgence, defined as an upswing in the effective reproduction number (R) of the contagion from subcritical to supercritical values, is fundamentally difficult to detect in real time. Inherent latencies in pathogen transmission, coupled with smaller and intrinsically noisier case incidence across periods of subcritical spread, mean that resurgence cannot be reliably detected without significant delays of the order of the generation time of the disease, even when case reporting is perfect. In contrast, epidemic suppression (where R falls from supercritical to subcritical values) may be ascertained 5–10 times faster due to the naturally larger incidence at which control actions are generally applied. We prove that these innate limits on detecting resurgence only worsen when spatial or demographic heterogeneities are incorporated. Consequently, we argue that resurgence is more effectively handled proactively, potentially at the expense of false alarms. Timely responses to recrudescent infections or emerging variants of concern are more likely to be possible when policy is informed by a greater quality and diversity of surveillance data than by further optimisation of the statistical models used to process routine outbreak data. Author summary: The timely detection of epidemic resurgence (i.e., upcoming waves of infected cases) is crucial for informing public health policy, providing valuable signals for implementing interventions and identifying emerging pathogenic variants or important population-level behavioural shifts. Increases in epidemic transmissibility, parametrised by the time-varying reproduction number, R, commonly signify resurgence. While many studies have improved computational methods for inferring R from case data, to enhance real-time resurgence detection, few have examined what limits, if any, fundamentally restrict our ability to perform this inference. We apply optimal Bayesian detection algorithms and sensitivity tests and discover that resurgent (upward) R-changes are intrinsically more difficult to detect than equivalent downward changes indicating control. This asymmetry derives from the often lower and stochastically noisier case numbers that associate with resurgence, and induces detection delays on the order of the disease generation time. We prove these delays only worsen if spatial or demographic differences in transmissibility are modelled. As these fundamental limits exist even if case data are perfect, we conclude that designing integrated surveillance systems that fuse potentially timelier data sources (e.g., wastewater) may be more important than improving R-estimation methodology and deduce that there may be merit (subject to false alarm costs) in conservative resurgence response initiatives. [ABSTRACT FROM AUTHOR]
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- 2022
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23. Are Skyline Plot-Based Demographic Estimates Overly Dependent on Smoothing Prior Assumptions?
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Parag, Kris V, Pybus, Oliver G, and Wu, Chieh-Hsi
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INFORMATION theory , *BAYESIAN field theory , *DEMOGRAPHIC change , *PHYLOGENY , *EXPERIMENTAL design - Abstract
In Bayesian phylogenetics, the coalescent process provides an informative framework for inferring changes in the effective size of a population from a phylogeny (or tree) of sequences sampled from that population. Popular coalescent inference approaches such as the Bayesian Skyline Plot , Skyride, and Skygrid all model these population size changes with a discontinuous, piecewise-constant function but then apply a smoothing prior to ensure that their posterior population size estimates transition gradually with time. These prior distributions implicitly encode extra population size information that is not available from the observed coalescent data or tree. Here, we present a novel statistic, |$\Omega$| , to quantify and disaggregate the relative contributions of the coalescent data and prior assumptions to the resulting posterior estimate precision. Our statistic also measures the additional mutual information introduced by such priors. Using |$\Omega$| we show that, because it is surprisingly easy to overparametrize piecewise-constant population models, common smoothing priors can lead to overconfident and potentially misleading inference, even under robust experimental designs. We propose |$\Omega$| as a useful tool for detecting when effective population size estimates are overly reliant on prior assumptions and for improving quantification of the uncertainty in those estimates.[Coalescent processes; effective population size; information theory; phylodynamics; prior assumptions; skyline plots.] [ABSTRACT FROM AUTHOR]
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- 2022
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24. Improved estimation of time-varying reproduction numbers at low case incidence and between epidemic waves.
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Parag, Kris V.
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KALMAN filtering , *FORWARD-backward algorithm , *COMMUNICABLE diseases , *DISEASE incidence , *MARKOV processes , *EPIDEMICS - Abstract
We construct a recursive Bayesian smoother, termed EpiFilter, for estimating the effective reproduction number, R, from the incidence of an infectious disease in real time and retrospectively. Our approach borrows from Kalman filtering theory, is quick and easy to compute, generalisable, deterministic and unlike many current methods, requires no change-point or window size assumptions. We model R as a flexible, hidden Markov state process and exactly solve forward-backward algorithms, to derive R estimates that incorporate all available incidence information. This unifies and extends two popular methods, EpiEstim, which considers past incidence, and the Wallinga-Teunis method, which looks forward in time. We find that this combination of maximising information and minimising assumptions significantly reduces the bias and variance of R estimates. Moreover, these properties make EpiFilter more statistically robust in periods of low incidence, where several existing methods can become destabilised. As a result, EpiFilter offers improved inference of time-varying transmission patterns that are advantageous for assessing the risk of upcoming waves of infection or the influence of interventions, in real time and at various spatial scales. Author summary: Inferring changes in the transmissibility of an infectious disease is crucial for understanding and controlling epidemic spread. The effective reproduction number, R, is widely used to assess transmissibility. R measures the average number of secondary cases caused by a primary case and has provided insight into many diseases including COVID-19. An upsurge in R can forewarn of upcoming infections, while suppression of R can indicate if public health interventions are working. Reliable estimates of temporal changes in R can contribute important evidence to policymaking. Popular R-inference methods, while powerful, can struggle when cases are few because data are noisy. This can limit detection of crucial variations in transmissibility that may occur, for example, when infections are waning or when analysing transmissibility over fine geographic scales. In this paper we improve the general reliability of R-estimates and specifically increase robustness when cases are few. By adapting principles from control engineering, we formulate EpiFilter, a novel method for inferring R in real time and retrospectively. EpiFilter can potentially double the information extracted from epidemic time-series (when compared to popular approaches), significantly filtering the noise within data to minimise both bias and uncertainty of R-estimates and enhance the detection of salient change-points in transmissibility. [ABSTRACT FROM AUTHOR]
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- 2021
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25. Spatiotemporal invasion dynamics of SARS-CoV-2 lineage B.1.1.7 emergence.
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Kraemer, Moritz U. G., Hill, Verity, Ruis, Christopher, Dellicour, Simon, Bajaj, Sumali, McCrone, John T., Baele, Guy, Parag, Kris V., Battle, Anya Lindström, Gutierrez, Bernardo, Jackson, Ben, Colquhoun, Rachel, O’Toole, Áine, Klein, Brennan, Vespignani, Alessandro, Volz, Erik, Faria, Nuno R., Aanensen, David M., Loman, Nicholas J., and du Plessis, Louis
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- 2021
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26. Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK.
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Plessis, Louis du, McCrone, John T., Zarebski, Alexander E., Hill, Verity, Ruis, Christopher, Gutierrez, Bernardo, Raghwani, Jayna, Ashworth, Jordan, Colquhoun, Rachel, Connor, Thomas R., Faria, Nuno R., Jackson, Ben, Loman, Nicholas J., O’Toole, Áine, Nicholls, Samuel M., Parag, Kris V., Scher, Emily, Vasylyeva, Tetyana I., Volz, Erik M., and Watts, Alexander
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- 2021
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27. An exact method for quantifying the reliability of end-of-epidemic declarations in real time.
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Parag, Kris V., Donnelly, Christl A., Jha, Rahul, and Thompson, Robin N.
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SOCIAL distancing , *COMMUNICABLE diseases , *TRAVEL warnings , *ECONOMIC sectors , *FORECASTING - Abstract
We derive and validate a novel and analytic method for estimating the probability that an epidemic has been eliminated (i.e. that no future local cases will emerge) in real time. When this probability crosses 0.95 an outbreak can be declared over with 95% confidence. Our method is easy to compute, only requires knowledge of the incidence curve and the serial interval distribution, and evaluates the statistical lifetime of the outbreak of interest. Using this approach, we rigorously show how the time-varying under-reporting of infected cases will artificially inflate the inferred probability of elimination, leading to premature (false-positive) end-of-epidemic declarations. Contrastingly, we prove that incorrectly identifying imported cases as local will deceptively decrease this probability, resulting in delayed (false-negative) declarations. Failing to sustain intensive surveillance during the later phases of an epidemic can therefore substantially mislead policymakers on when it is safe to remove travel bans or relax quarantine and social distancing advisories. World Health Organisation guidelines recommend fixed (though disease-specific) waiting times for end-of-epidemic declarations that cannot accommodate these variations. Consequently, there is an unequivocal need for more active and specialised metrics for reliably identifying the conclusion of an epidemic. Author summary: Deciding on when to declare an infectious disease epidemic over is an important and non-trivial problem. Early declarations can mean that interventions such as lockdowns, social distancing advisories and travel bans are relaxed prematurely, elevating the risk of additional waves of the disease. Late declarations can unnecessarily delay the re-opening of key economic sectors, for example trade, tourism and agriculture, potentially resulting in significant financial and livelihood losses. Here we develop and test a novel and exact data-driven method for optimising the timing of end-of-epidemic declarations. Our approach converts observations of infected cases up to any given time into a prediction of the likelihood that the epidemic is over at that time. Using this method, we quantify the reliability of end-of-epidemic declarations in real time, under ideal case surveillance, showing that it can depend strongly on past infection numbers. We then prove that failing to compensate for practical issues such as the time-varying under-reporting and importing of cases necessarily results in premature and delayed declarations, respectively. These variations and biases cannot be accommodated by current worldwide declaration guidelines. Sustained and intensive surveillance coupled with more adaptive declaration metrics are vital if informed end-of-epidemic declarations are to be made. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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28. Jointly Inferring the Dynamics of Population Size and Sampling Intensity from Molecular Sequences.
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Parag, Kris V, Plessis, Louis du, and Pybus, Oliver G
- Abstract
Estimating past population dynamics from molecular sequences that have been sampled longitudinally through time is an important problem in infectious disease epidemiology, molecular ecology, and macroevolution. Popular solutions, such as the skyline and skygrid methods, infer past effective population sizes from the coalescent event times of phylogenies reconstructed from sampled sequences but assume that sequence sampling times are uninformative about population size changes. Recent work has started to question this assumption by exploring how sampling time information can aid coalescent inference. Here, we develop, investigate, and implement a new skyline method, termed the epoch sampling skyline plot (ESP), to jointly estimate the dynamics of population size and sampling rate through time. The ESP is inspired by real-world data collection practices and comprises a flexible model in which the sequence sampling rate is proportional to the population size within an epoch but can change discontinuously between epochs. We show that the ESP is accurate under several realistic sampling protocols and we prove analytically that it can at least double the best precision achievable by standard approaches. We generalize the ESP to incorporate phylogenetic uncertainty in a new Bayesian package (BESP) in BEAST2. We re-examine two well-studied empirical data sets from virus epidemiology and molecular evolution and find that the BESP improves upon previous coalescent estimators and generates new, biologically useful insights into the sampling protocols underpinning these data sets. Sequence sampling times provide a rich source of information for coalescent inference that will become increasingly important as sequence collection intensifies and becomes more formalized. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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29. Using information theory to optimise epidemic models for real-time prediction and estimation.
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Parag, Kris V. and Donnelly, Christl A.
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- *
INFORMATION theory , *ZIKA virus infections , *EBOLA virus disease , *COVID-19 pandemic , *BRANCHING processes , *BASIC reproduction number - Abstract
The effective reproduction number, Rt, is a key time-varying prognostic for the growth rate of any infectious disease epidemic. Significant changes in Rt can forewarn about new transmissions within a population or predict the efficacy of interventions. Inferring Rt reliably and in real-time from observed time-series of infected (demographic) data is an important problem in population dynamics. The renewal or branching process model is a popular solution that has been applied to Ebola and Zika virus disease outbreaks, among others, and is currently being used to investigate the ongoing COVID-19 pandemic. This model estimates Rt using a heuristically chosen piecewise function. While this facilitates real-time detection of statistically significant Rt changes, inference is highly sensitive to the function choice. Improperly chosen piecewise models might ignore meaningful changes or over-interpret noise-induced ones, yet produce visually reasonable estimates. No principled piecewise selection scheme exists. We develop a practical yet rigorous scheme using the accumulated prediction error (APE) metric from information theory, which deems the model capable of describing the observed data using the fewest bits as most justified. We derive exact posterior prediction distributions for infected population size and integrate these within an APE framework to obtain an exact and reliable method for identifying the piecewise function best supported by available epidemic data. We find that this choice optimises short-term prediction accuracy and can rapidly detect salient fluctuations in Rt, and hence the infected population growth rate, in real-time over the course of an unfolding epidemic. Moreover, we emphasise the need for formal selection by exposing how common heuristic choices, which seem sensible, can be misleading. Our APE-based method is easily computed and broadly applicable to statistically similar models found in phylogenetics and macroevolution, for example. Our results explore the relationships among estimate precision, forecast reliability and model complexity. Author summary: Understanding how the population of infected individuals (which may be humans, animals or plants) fluctuates in size over the course of an epidemic is an important problem in epidemiology and ecology. The effective reproduction number, R, provides an intuitive and useful way of describing these fluctuations by characterising the growth rate of the infected population. An R > 1 signifies a burgeoning epidemic whereas R < 1 indicates a declining one. Public health agencies often use R to inform or corroborate vaccination and quarantine policies. However, popular approaches to inferring R from epidemic data make heuristic choices, which may lead to visually reasonable estimates that are deceptive or unreliable. By adapting mathematical tools from information theory, we develop a general and principled scheme for estimating R in a data-justified way. Our method exposes the pitfalls of heuristic estimates and provides an easily computable correction that also maximises our ability to predict upcoming population fluctuations. Our work is widely applicable to similar inference problems found in evolution and genetics, demonstrably useful for reliably analysing emerging epidemics in real time and highlights how abstract mathematical concepts can inspire novel and practical biological solutions, showcasing the importance of multidisciplinary research. [ABSTRACT FROM AUTHOR]
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- 2020
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30. On signalling and estimation limits for molecular birth-processes.
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Parag, Kris V
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QUEUING theory , *CYTOLOGY - Abstract
• Achievable precision on a signalling pathway is bounded by its capacity. • For birth-processes, a signalling motif called birth-following is found optimal. • It achieves better precision than this bound, if certain rate constraints hold. • Different constraints implying distinct precisions can map to equal capacities. • The capacity-precision relationship is not simple, even for simple networks. Understanding and uncovering the mechanisms or motifs that molecular networks employ to regulate noise is a key problem in cell biology. As it is often difficult to obtain direct and detailed insight into these mechanisms, many studies instead focus on assessing the best precision attainable on the signalling pathways that compose these networks. Molecules signal one another over such pathways to solve noise regulating estimation and control problems. Quantifying the maximum precision of these solutions delimits what is achievable and allows hypotheses about underlying motifs to be tested without requiring detailed biological knowledge. The pathway capacity, which defines the maximum rate of transmitting information along it, is a widely used proxy for precision. Here it is shown, for estimation problems involving elementary yet biologically relevant birth-process networks, that capacity can be surprisingly misleading. A time-optimal signalling motif, called birth-following, is derived and proven to better the precision expected from the capacity, provided the maximum signalling rate constraint is large and the mean one above a certain threshold. When the maximum constraint is relaxed, perfect estimation is predicted by the capacity. However, the true achievable precision is found highly variable and sensitive to the mean constraint. Since the same capacity can map to different combinations of rate constraints, it can only equivocally measure precision. Deciphering the rate constraints on a signalling pathway may therefore be more important than computing its capacity. [ABSTRACT FROM AUTHOR]
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- 2019
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31. Exact Bayesian inference for phylogenetic birth-death models.
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Parag, Kris V and Pybus, Oliver G
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- *
PHYLOGENY , *BAYESIAN analysis , *GENETIC engineering , *MARKOV processes , *MONTE Carlo method - Abstract
Motivation Inferring the rates of change of a population from a reconstructed phylogeny of genetic sequences is a central problem in macro-evolutionary biology, epidemiology and many other disciplines. A popular solution involves estimating the parameters of a birth-death process (BDP), which links the shape of the phylogeny to its birth and death rates. Modern BDP estimators rely on random Markov chain Monte Carlo (MCMC) sampling to infer these rates. Such methods, while powerful and scalable, cannot be guaranteed to converge, leading to results that may be hard to replicate or difficult to validate. Results We present a conceptually and computationally different parametric BDP inference approach using flexible and easy to implement Snyder filter (SF) algorithms. This method is deterministic so its results are provable, guaranteed and reproducible. We validate the SF on constant rate BDPs and find that it solves BDP likelihoods known to produce robust estimates. We then examine more complex BDPs with time-varying rates. Our estimates compare well with a recently developed parametric MCMC inference method. Lastly, we perform model selection on an empirical Agamid species phylogeny, obtaining results consistent with the literature. The SF makes no approximations, beyond those required for parameter quantization and numerical integration and directly computes the posterior distribution of model parameters. It is a promising alternative inference algorithm that may serve either as a standalone Bayesian estimator or as a useful diagnostic reference for validating more involved MCMC strategies. Availability and implementation The Snyder filter is implemented in Matlab and the time-varying BDP models are simulated in R. The source code and data are freely available at https://github.com/kpzoo/snyder-birth-death-code. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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32. Point process analysis of noise in early invertebrate vision.
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Parag, Kris V. and Vinnicombe, Glenn
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- *
NOISE , *INVERTEBRATES , *PHOTONS , *LIGHT intensity , *G proteins - Abstract
Noise is a prevalent and sometimes even dominant aspect of many biological processes. While many natural systems have adapted to attenuate or even usefully integrate noise, the variability it introduces often still delimits the achievable precision across biological functions. This is particularly so for visual phototransduction, the process responsible for converting photons of light into usable electrical signals (quantum bumps). Here, randomness of both the photon inputs (regarded as extrinsic noise) and the conversion process (intrinsic noise) are seen as two distinct, independent and significant limitations on visual reliability. Past research has attempted to quantify the relative effects of these noise sources by using approximate methods that do not fully account for the discrete, point process and time ordered nature of the problem. As a result the conclusions drawn from these different approaches have led to inconsistent expositions of phototransduction noise performance. This paper provides a fresh and complete analysis of the relative impact of intrinsic and extrinsic noise in invertebrate phototransduction using minimum mean squared error reconstruction techniques based on Bayesian point process (Snyder) filters. An integrate-fire based algorithm is developed to reliably estimate photon times from quantum bumps and Snyder filters are then used to causally estimate random light intensities both at the front and back end of the phototransduction cascade. Comparison of these estimates reveals that the dominant noise source transitions from extrinsic to intrinsic as light intensity increases. By extending the filtering techniques to account for delays, it is further found that among the intrinsic noise components, which include bump latency (mean delay and jitter) and shape (amplitude and width) variance, it is the mean delay that is critical to noise performance. As the timeliness of visual information is important for real-time action, this delay could potentially limit the speed at which invertebrates can respond to stimuli. Consequently, if one wants to increase visual fidelity, reducing the photoconversion lag is much more important than improving the regularity of the electrical signal. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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33. Optimal point process filtering and estimation of the coalescent process.
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Parag, Kris V. and Pybus, Oliver G.
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- *
POPULATION genetics -- Mathematical models , *MARKOV chain Monte Carlo , *GAUSSIAN processes , *BAYESIAN analysis , *DEMOGRAPHIC surveys - Abstract
The coalescent process is a widely used approach for inferring the demographic history of a population, from samples of its genetic diversity. Several parametric and non-parametric coalescent inference methods, involving Markov chain Monte Carlo, Gaussian processes, and other algorithms, already exist. However, these techniques are not always easy to adapt and apply, thus creating a need for alternative methodologies. We introduce the Bayesian Snyder filter as an easily implementable and flexible minimum mean square error estimator for parametric demographic functions on fixed genealogies. By reinterpreting the coalescent as a self-exciting Markov process, we show that the Snyder filter can be applied to both isochronously and heterochronously sampled datasets. We analytically solve the filter equations for the constant population size Kingman coalescent, derive expressions for its mean squared estimation error, and estimate its robustness to prior distribution specification. For populations with deterministically time-varying size we numerically solve the Snyder equations, and test this solution on common demographic models. We find that the Snyder filter accurately recovers the true demographic history for these models. We also apply the filter to a well-studied, dataset of hepatitis C virus sequences and show that the filter compares well to a popular phylodynamic inference method. The Snyder filter is an exact (given discretised priors, it does not approximate the posterior) and direct Bayesian estimation method that has the potential to become a useful alternative tool for coalescent inference. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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34. Using digital traces to build prospective and real-time county-level early warning systems to anticipate COVID-19 outbreaks in the United States.
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Stolerman, Lucas M., Clemente, Leonardo, Poirier, Canelle, Parag, Kris V., Majumder, Atreyee, Masyn, Serge, Resch, Bernd, and Santillana, Mauricio
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- *
COVID-19 pandemic , *HEALTH facilities , *VACCINATION complications - Abstract
The article discuses the usage of internet based digital traces for early detection of Coronavirus disease 2019 (COVID-19) outbreak in U.S. It is reported that statistical and machine learning approaches has explored how to incorporate disease related internet search data to track and forecast COVID-19 activity with some limitations documented. It is further reported that proposed methods leverage information from multiple internet-based data sources and serve as proxies of human behavior.
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- 2023
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35. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence.
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Sabino, Ester C, Buss, Lewis F, Carvalho, Maria P S, Prete, Carlos A, Crispim, Myuki A E, Fraiji, Nelson A, Pereira, Rafael H M, Parag, Kris V, da Silva Peixoto, Pedro, Kraemer, Moritz U G, Oikawa, Marcio K, Salomon, Tassila, Cucunuba, Zulma M, Castro, Márcia C, de Souza Santos, Andreza Aruska, Nascimento, Vítor H, Pereira, Henrique S, Ferguson, Neil M, Pybus, Oliver G, and Kucharski, Adam
- Subjects
- *
COVID-19 , *MEDICAL personnel , *SEROPREVALENCE , *RESEARCH funding - Abstract
After initially containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many European and Asian countries had a resurgence of COVID-19 consistent with a large proportion of the population remaining susceptible to the virus after the first epidemic wave.[1] By contrast, in Manaus, Brazil, a study of blood donors indicated that 76% (95% CI 67-98) of the population had been infected with SARS-CoV-2 by October, 2020.[2] High attack rates of SARS-CoV-2 were also estimated in population-based samples from other locations in the Amazon Basin - eg, Iquitos, Peru 70% (67-73).[3] The estimated SARS-CoV-2 attack rate in Manaus would be above the theoretical herd immunity threshold (67%), given a basic case reproduction number (R SB 0 sb ) of 3.[4] In this context, the abrupt increase in the number of COVID-19 hospital admissions in Manaus during January, 2021 (3431 in Jan 1-19, 2021, vs 552 in Dec 1-19, 2020) is unexpected and of concern (figure).[[5]] After a large epidemic that peaked in late April, 2020, COVID-19 hospitalisations in Manaus remained stable and fairly low for 7 months from May to November, despite the relaxation of COVID-19 control measures during that period (figure). However, most of the SARS-CoV-2 infections in Manaus occurred 7-8 months before the resurgence in January, 2021; this is longer than the period covered by the UK study,[13] but nonetheless suggests that waning immunity alone is unlikely to fully explain the recent resurgence. Graph: Figure COVID-19 hospitalisations, excess deaths, and Rt in Manaus, Brazil, 2020-21(A) Dark lines are the 7-day rolling averages and lighter lines are the daily time series of COVID-19 hospitalisations and excess deaths. [Extracted from the article]
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- 2021
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36. A Bayesian nonparametric method for detecting rapid changes in disease transmission.
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Creswell, Richard, Robinson, Martin, Gavaghan, David, Parag, Kris V., Lei, Chon Lok, and Lambert, Ben
- Subjects
- *
INFECTIOUS disease transmission , *COVID-19 pandemic , *DISEASE outbreaks , *COMMUNICABLE diseases , *EPIDEMIOLOGY , *BASIC reproduction number , *EPIDEMICS - Abstract
Whether an outbreak of infectious disease is likely to grow or dissipate is determined through the time-varying reproduction number, R t. Real-time or retrospective identification of changes in R t following the imposition or relaxation of interventions can thus contribute important evidence about disease transmission dynamics which can inform policymaking. Here, we present a method for estimating shifts in R t within a renewal model framework. Our method, which we call EpiCluster, is a Bayesian nonparametric model based on the Pitman–Yor process. We assume that R t is piecewise-constant, and the incidence data and priors determine when or whether R t should change and how many times it should do so throughout the series. We also introduce a prior which induces sparsity over the number of changepoints. Being Bayesian, our approach yields a measure of uncertainty in R t and its changepoints. EpiCluster is fast, straightforward to use, and we demonstrate that it provides automated detection of rapid changes in transmission, either in real-time or retrospectively, for synthetic data series where the R t profile is known. We illustrate the practical utility of our method by fitting it to case data of outbreaks of COVID-19 in Australia and Hong Kong, where it finds changepoints coinciding with the imposition of non-pharmaceutical interventions. Bayesian nonparametric methods, such as ours, allow the volume and complexity of the data to dictate the number of parameters required to approximate the process and should find wide application in epidemiology. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics". • Identifying changes in transmission is important for epidemic control strategies. • We model the time-varying reproduction number, R t , as piecewise-constant. • We develop a Bayesian nonparametric method (EpiCluster) to infer changepoints in R t. • Our method is adept at inferring changepoints on simulated series. • EpiCluster identifies abrupt changes in R t for COVID-19 outbreaks in several countries. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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37. Host behaviour driven by awareness of infection risk amplifies the chance of superspreading events.
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Parag KV and Thompson RN
- Subjects
- Humans, Basic Reproduction Number, Models, Biological, COVID-19 transmission, COVID-19 epidemiology, SARS-CoV-2
- Abstract
We demonstrate that heterogeneity in the perceived risks associated with infection within host populations amplifies chances of superspreading during the crucial early stages of epidemics. Under this behavioural model, individuals less concerned about dangers from infection are more likely to be infected and attend larger sized (riskier) events, where we assume event sizes remain unchanged. For directly transmitted diseases such as COVID-19, this leads to infections being introduced at rates above the population prevalence to those events most conducive to superspreading. We develop an interpretable, computational framework for evaluating within-event risks and derive a small-scale reproduction number measuring how the infections generated at an event depend on transmission heterogeneities and numbers of introductions. This generalizes previous frameworks and quantifies how event-scale patterns and population-level characteristics relate. As event duration and size grow, our reproduction number converges to the basic reproduction number. We illustrate that even moderate levels of heterogeneity in the perceived risks of infection substantially increase the likelihood of disproportionately large clusters of infections occurring at larger events, despite fixed overall disease prevalence. We show why collecting data linking host behaviour and event attendance is essential for accurately assessing the risks posed by invading pathogens in emerging stages of outbreaks.
- Published
- 2024
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38. Correction: Implementation of Genomic Surveillance of SARS-CoV-2 in the Caribbean: Lessons learned for sustainability in resource-limited settings.
- Author
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Sahadeo NSD, Nicholls S, Moreira FRR, O'Toole Á, Ramkissoon V, Whittaker C, Hill V, McCrone JT, Mohammed N, Ramjag A, Jordan AB, Hill SC, Singh R, Nathaniel-Girdharrie SM, Hinds A, Ramkissoon N, Parag KV, Nandram N, Parasram R, Khan-Mohammed Z, Edghill L, Indar L, Andrewin A, Sealey-Thomas R, McMillan P, Oyinloye A, George K, Potter I, Lee J, Johnson D, Charles S, Singh N, Bisesor-McKenzie J, Laws H, Belmar-George S, Keizer-Beache S, Greenaway-Duberry S, Ashwood N, Foster JE, Georges K, Naidu R, Ivey M, Giddings S, Haraksingh R, Ramsubhag A, Jayaraman J, Chinnadurai C, Oura C, Pybus OG, St John J, Gonzalez-Escobar G, Faria NR, and Carrington CVF
- Abstract
[This corrects the article DOI: 10.1371/journal.pgph.0001455.]., (Copyright: © 2023 Sahadeo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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39. Implementation of genomic surveillance of SARS-CoV-2 in the Caribbean: Lessons learned for sustainability in resource-limited settings.
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Sahadeo NSD, Nicholls S, Moreira FRR, O'Toole Á, Ramkissoon V, Whittaker C, Hill V, McCrone JT, Mohammed N, Ramjag A, Brown Jordan A, Hill SC, Singh R, Nathaniel-Girdharrie SM, Hinds A, Ramkissoon N, Parag KV, Nandram N, Parasram R, Khan-Mohammed Z, Edghill L, Indar L, Andrewin A, Sealey-Thomas R, McMillan P, Oyinloye A, George K, Potter I, Lee J, Johnson D, Charles S, Singh N, Bisesor-McKenzie J, Laws H, Belmar-George S, Keizer-Beache S, Greenaway-Duberry S, Ashwood N, Foster JE, Georges K, Naidu R, Ivey M, Giddings S, Haraksingh R, Ramsubhag A, Jayaraman J, Chinnadurai C, Oura C, Pybus OG, St John J, Gonzalez-Escobar G, Faria NR, and Carrington CVF
- Abstract
The COVID-19 pandemic highlighted the importance of global genomic surveillance to monitor the emergence and spread of SARS-CoV-2 variants and inform public health decision-making. Until December 2020 there was minimal capacity for viral genomic surveillance in most Caribbean countries. To overcome this constraint, the COVID-19: Infectious disease Molecular epidemiology for PAthogen Control & Tracking (COVID-19 IMPACT) project was implemented to establish rapid SARS-CoV-2 whole genome nanopore sequencing at The University of the West Indies (UWI) in Trinidad and Tobago (T&T) and provide needed SARS-CoV-2 sequencing services for T&T and other Caribbean Public Health Agency Member States (CMS). Using the Oxford Nanopore Technologies MinION sequencing platform and ARTIC network sequencing protocols and bioinformatics pipeline, a total of 3610 SARS-CoV-2 positive RNA samples, received from 17 CMS, were sequenced in-situ during the period December 5th 2020 to December 31st 2021. Ninety-one Pango lineages, including those of five variants of concern (VOC), were identified. Genetic analysis revealed at least 260 introductions to the CMS from other global regions. For each of the 17 CMS, the percentage of reported COVID-19 cases sequenced by the COVID-19 IMPACT laboratory ranged from 0·02% to 3·80% (median = 1·12%). Sequences submitted to GISAID by our study represented 73·3% of all SARS-CoV-2 sequences from the 17 CMS available on the database up to December 31st 2021. Increased staffing, process and infrastructural improvement over the course of the project helped reduce turnaround times for reporting to originating institutions and sequence uploads to GISAID. Insights from our genomic surveillance network in the Caribbean region directly influenced non-pharmaceutical countermeasures in the CMS countries. However, limited availability of associated surveillance and clinical data made it challenging to contextualise the observed SARS-CoV-2 diversity and evolution, highlighting the need for development of infrastructure for collecting and integrating genomic sequencing data and sample-associated metadata., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sahadeo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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40. Are Skyline Plot-Based Demographic Estimates Overly Dependent on Smoothing Prior Assumptions?
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Parag KV, Pybus OG, and Wu CH
- Subjects
- Bayes Theorem, Phylogeny, Population Density, Models, Genetic
- Abstract
In Bayesian phylogenetics, the coalescent process provides an informative framework for inferring changes in the effective size of a population from a phylogeny (or tree) of sequences sampled from that population. Popular coalescent inference approaches such as the Bayesian Skyline Plot, Skyride, and Skygrid all model these population size changes with a discontinuous, piecewise-constant function but then apply a smoothing prior to ensure that their posterior population size estimates transition gradually with time. These prior distributions implicitly encode extra population size information that is not available from the observed coalescent data or tree. Here, we present a novel statistic, $\Omega$, to quantify and disaggregate the relative contributions of the coalescent data and prior assumptions to the resulting posterior estimate precision. Our statistic also measures the additional mutual information introduced by such priors. Using $\Omega$ we show that, because it is surprisingly easy to overparametrize piecewise-constant population models, common smoothing priors can lead to overconfident and potentially misleading inference, even under robust experimental designs. We propose $\Omega$ as a useful tool for detecting when effective population size estimates are overly reliant on prior assumptions and for improving quantification of the uncertainty in those estimates.[Coalescent processes; effective population size; information theory; phylodynamics; prior assumptions; skyline plots.]., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Systematic Biologists.)
- Published
- 2021
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41. Deciphering early-warning signals of SARS-CoV-2 elimination and resurgence from limited data at multiple scales.
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Parag KV, Cowling BJ, and Donnelly CA
- Subjects
- Australia, Humans, New Zealand, SARS-CoV-2, COVID-19, Communicable Diseases
- Abstract
Inferring the transmission potential of an infectious disease during low-incidence periods following epidemic waves is crucial for preparedness. In such periods, scarce data may hinder existing inference methods, blurring early-warning signals essential for discriminating between the likelihoods of resurgence versus elimination. Advanced insight into whether elevating caseloads (requiring swift community-wide interventions) or local elimination (allowing controls to be relaxed or refocussed on case-importation) might occur can separate decisive from ineffective policy. By generalizing and fusing recent approaches, we propose a novel early-warning framework that maximizes the information extracted from low-incidence data to robustly infer the chances of sustained local transmission or elimination in real time, at any scale of investigation (assuming sufficiently good surveillance). Applying this framework, we decipher hidden disease-transmission signals in prolonged low-incidence COVID-19 data from New Zealand, Hong Kong and Victoria, Australia. We uncover how timely interventions associate with averting resurgent waves, support official elimination declarations and evidence the effectiveness of the rapid, adaptive COVID-19 responses employed in these regions.
- Published
- 2021
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42. Sub-spreading events limit the reliable elimination of heterogeneous epidemics.
- Author
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Parag KV
- Subjects
- Incidence, Epidemics
- Abstract
We show that sub-spreading events, i.e. transmission events in which an infection propagates to few or no individuals, can be surprisingly important for defining the lifetime of an infectious disease epidemic and hence its waiting time to elimination or fade-out, measured from the time-point of its last observed case. While limiting super-spreading promotes more effective control when cases are growing, we find that when incidence is waning, curbing sub-spreading is more important for achieving reliable elimination of the epidemic. Controlling super-spreading in this low-transmissibility phase offers diminishing returns over non-selective, population-wide measures. By restricting sub-spreading, we efficiently dampen remaining variations among the reproduction numbers of infectious events, which minimizes the risk of premature and late end-of-epidemic declarations. Because case-ascertainment or reporting rates can be modelled in exactly the same way as control policies, we concurrently show that the under-reporting of sub-spreading events during waning phases will engender overconfident assessments of epidemic elimination. While controlling sub-spreading may not be easily realized, the likely neglecting of these events by surveillance systems could result in unexpectedly risky end-of-epidemic declarations. Super-spreading controls the size of the epidemic peak but sub-spreading mediates the variability of its tail.
- Published
- 2021
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43. Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK.
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du Plessis L, McCrone JT, Zarebski AE, Hill V, Ruis C, Gutierrez B, Raghwani J, Ashworth J, Colquhoun R, Connor TR, Faria NR, Jackson B, Loman NJ, O'Toole Á, Nicholls SM, Parag KV, Scher E, Vasylyeva TI, Volz EM, Watts A, Bogoch II, Khan K, Aanensen DM, Kraemer MUG, Rambaut A, and Pybus OG
- Subjects
- COVID-19 prevention & control, COVID-19 transmission, Chain of Infection, Communicable Disease Control, Communicable Diseases, Imported epidemiology, Communicable Diseases, Imported virology, Epidemics, Humans, Phylogeny, Travel, United Kingdom epidemiology, COVID-19 epidemiology, COVID-19 virology, Genome, Viral, SARS-CoV-2 genetics
- Abstract
The United Kingdom's COVID-19 epidemic during early 2020 was one of world's largest and was unusually well represented by virus genomic sampling. We determined the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes, including 26,181 from the UK sampled throughout the country's first wave of infection. Using large-scale phylogenetic analyses combined with epidemiological and travel data, we quantified the size, spatiotemporal origins, and persistence of genetically distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whereas lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2021
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44. Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic.
- Author
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Buss LF, Prete CA Jr, Abrahim CMM, Mendrone A Jr, Salomon T, de Almeida-Neto C, França RFO, Belotti MC, Carvalho MPSS, Costa AG, Crispim MAE, Ferreira SC, Fraiji NA, Gurzenda S, Whittaker C, Kamaura LT, Takecian PL, da Silva Peixoto P, Oikawa MK, Nishiya AS, Rocha V, Salles NA, de Souza Santos AA, da Silva MA, Custer B, Parag KV, Barral-Netto M, Kraemer MUG, Pereira RHM, Pybus OG, Busch MP, Castro MC, Dye C, Nascimento VH, Faria NR, and Sabino EC
- Subjects
- Adolescent, Adult, Aged, Blood Donors, Brazil epidemiology, COVID-19 blood, COVID-19 mortality, Epidemiological Monitoring, Female, Humans, Male, Middle Aged, SARS-CoV-2 immunology, Seroepidemiologic Studies, Young Adult, Antibodies, Viral blood, COVID-19 epidemiology, Epidemics, Immunoglobulin G blood, SARS-CoV-2 isolation & purification
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly in Manaus, the capital of Amazonas state in northern Brazil. The attack rate there is an estimate of the final size of the largely unmitigated epidemic that occurred in Manaus. We use a convenience sample of blood donors to show that by June 2020, 1 month after the epidemic peak in Manaus, 44% of the population had detectable immunoglobulin G (IgG) antibodies. Correcting for cases without a detectable antibody response and for antibody waning, we estimate a 66% attack rate in June, rising to 76% in October. This is higher than in São Paulo, in southeastern Brazil, where the estimated attack rate in October was 29%. These results confirm that when poorly controlled, COVID-19 can infect a large proportion of the population, causing high mortality., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2021
- Full Text
- View/download PDF
45. SARS-CoV-2 infection prevalence on repatriation flights from Wuhan City, China.
- Author
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Thompson HA, Imai N, Dighe A, Ainslie KEC, Baguelin M, Bhatia S, Bhatt S, Boonyasiri A, Boyd O, Brazeau NF, Cattarino L, Cooper LV, Coupland H, Cucunuba Z, Cuomo-Dannenburg G, Djaafara B, Dorigatti I, van Elsland S, FitzJohn R, Fu H, Gaythorpe KAM, Green W, Hallett T, Hamlet A, Haw D, Hayes S, Hinsley W, Jeffrey B, Knock E, Laydon DJ, Lees J, Mangal TD, Mellan T, Mishra S, Mousa A, Nedjati-Gilani G, Nouvellet P, Okell L, Parag KV, Ragonnet-Cronin M, Riley S, Unwin HJT, Verity R, Vollmer M, Volz E, Walker PGT, Walters C, Wang H, Wang Y, Watson OJ, Whittaker C, Whittles LK, Winskill P, Xi X, Donnelly CA, and Ferguson NM
- Subjects
- COVID-19 Nucleic Acid Testing methods, COVID-19 Nucleic Acid Testing statistics & numerical data, China epidemiology, Epidemiologic Measurements, Humans, International Health Regulations organization & administration, Prevalence, Travel Medicine methods, Travel Medicine trends, United Kingdom epidemiology, Air Travel statistics & numerical data, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 transmission, Communicable Disease Control methods, Epidemiological Monitoring, SARS-CoV-2 isolation & purification
- Published
- 2020
- Full Text
- View/download PDF
46. Comparative micro-epidemiology of pathogenic avian influenza virus outbreaks in a wild bird population.
- Author
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Hill SC, Hansen R, Watson S, Coward V, Russell C, Cooper J, Essen S, Everest H, Parag KV, Fiddaman S, Reid S, Lewis N, Brookes SM, Smith AL, Sheldon B, Perrins CM, Brown IH, and Pybus OG
- Subjects
- Animals, Animals, Wild virology, Anseriformes virology, Disease Outbreaks, Influenza A Virus, H5N1 Subtype classification, Influenza A Virus, H5N1 Subtype genetics, Influenza A virus classification, Influenza in Birds epidemiology, Influenza in Birds mortality, Phylogeny, United Kingdom epidemiology, Influenza A Virus, H5N1 Subtype isolation & purification, Influenza A virus isolation & purification, Influenza in Birds virology
- Abstract
Understanding the epidemiological dynamics of highly pathogenic avian influenza virus (HPAIV) in wild birds is crucial for guiding effective surveillance and control measures. The spread of H5 HPAIV has been well characterized over large geographical and temporal scales. However, information about the detailed dynamics and demographics of individual outbreaks in wild birds is rare and important epidemiological parameters remain unknown. We present data from a wild population of long-lived birds (mute swans; Cygnus olor) that has experienced three outbreaks of related H5 HPAIVs in the past decade, specifically, H5N1 (2007), H5N8 (2016) and H5N6 (2017). Detailed demographic data were available and intense sampling was conducted before and after the outbreaks; hence the population is unusually suitable for exploring the natural epidemiology, evolution and ecology of HPAIV in wild birds. We show that key epidemiological features remain remarkably consistent across multiple outbreaks, including the timing of virus incursion and outbreak duration, and the presence of a strong age-structure in morbidity that likely arises from an equivalent age-structure in immunological responses. The predictability of these features across a series of outbreaks in a complex natural population is striking and contributes to our understanding of HPAIV in wild birds. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.
- Published
- 2019
- Full Text
- View/download PDF
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