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Journal ArticleDOI

Estimating the impact of school closure on influenza transmission from Sentinel data

TL;DR: It is shown that holidays lead to a 20–29% reduction in the rate at which influenza is transmitted to children, but that they have no detectable effect on the contact patterns of adults, as well as predicting the effect of school closure during a pandemic.
Abstract: The threat posed by the highly pathogenic H5N1 influenza virus requires public health authorities to prepare for a human pandemic. Although pre-pandemic vaccines and antiviral drugs might significantly reduce illness rates, their stockpiling is too expensive to be practical for many countries. Consequently, alternative control strategies, based on non-pharmaceutical interventions, are a potentially attractive policy option. School closure is the measure most often considered. The high social and economic costs of closing schools for months make it an expensive and therefore controversial policy, and the current absence of quantitative data on the role of schools during influenza epidemics means there is little consensus on the probable effectiveness of school closure in reducing the impact of a pandemic. Here, from the joint analysis of surveillance data and holiday timing in France, we quantify the role of schools in influenza epidemics and predict the effect of school closure during a pandemic. We show that holidays lead to a 20-29% reduction in the rate at which influenza is transmitted to children, but that they have no detectable effect on the contact patterns of adults. Holidays prevent 16-18% of seasonal influenza cases (18-21% in children). By extrapolation, we find that prolonged school closure during a pandemic might reduce the cumulative number of cases by 13-17% (18-23% in children) and peak attack rates by up to 39-45% (47-52% in children). The impact of school closure would be reduced if it proved difficult to maintain low contact rates among children for a prolonged period.
Citations
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DOI
16 Mar 2020
TL;DR: Neil M Ferguson, Daniel Laydon, Gemma Nedjati-Gilani, Natsuko Imai, Kylie Ainslie, Sangeeta Bhatia, Adhiratha Boonyasiri, Zulma Cucunubá, Gina Cuomo-Dannenburg, Amy Dighe, Ilaria Dorigatti, Han Fu, Katy Gaythorpe, Will Green, Arran Hamlet, Wes Hinsley, Lucy C Okell.
Abstract: The global impact of COVID-19 has been profound, and the public health threat it represents is the most serious seen in a respiratory virus since the 1918 H1N1 influenza pandemic. Here we present the results of epidemiological modelling which has informed policymaking in the UK and other countries in recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number of public health measures – so-called non-pharmaceutical interventions (NPIs) – aimed at reducing contact rates in the population and thereby reducing transmission of the virus. In the results presented here, we apply a previously published microsimulation model to two countries: the UK (Great Britain specifically) and the US. We conclude that the effectiveness of any one intervention in isolation is likely to be limited, requiring multiple interventions to be combined to have a substantial impact on transmission. Two fundamental strategies are possible: (a) mitigation, which focuses on slowing but not necessarily stopping epidemic spread – reducing peak healthcare demand while protecting those most at risk of severe disease from infection, and (b) suppression, which aims to reverse epidemic growth, reducing case numbers to low levels and maintaining that situation indefinitely. Each policy has major challenges. We find that that optimal mitigation policies (combining home isolation of suspect cases, home quarantine of those living in the same household as suspect cases, and social distancing of the elderly and others at most risk of severe disease) might reduce peak healthcare demand by 2/3 and deaths by half. However, the resulting mitigated epidemic would still likely result in hundreds of thousands of deaths and health systems (most notably intensive care units) being overwhelmed many times over. For countries able to achieve it, this leaves suppression as the preferred policy option. We show that in the UK and US context, suppression will minimally require a combination of social distancing of the entire population, home isolation of cases and household quarantine of their family members. This may need to be supplemented by school and university closures, though it should be recognised that such closures may have negative impacts on health systems due to increased absenteeism. The major challenge of suppression is that this type of intensive intervention package – or something equivalently effective at reducing transmission – will need to be maintained until a vaccine becomes available (potentially 18 months or more) – given that we predict that transmission will quickly rebound if interventions are relaxed. We show that intermittent social distancing – triggered by trends in disease surveillance – may allow interventions to be relaxed temporarily in relative short time windows, but measures will need to be reintroduced if or when case numbers rebound. Last, while experience in China and now South Korea show that suppression is possible in the short term, it remains to be seen whether it is possible long-term, and whether the social and economic costs of the interventions adopted thus far can be reduced.

2,908 citations

Journal ArticleDOI
TL;DR: It is found that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low.
Abstract: The COVID-19 pandemic has shown a markedly low proportion of cases among children1–4. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from China, Italy, Japan, Singapore, Canada and South Korea. We estimate that susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years, and that clinical symptoms manifest in 21% (95% credible interval: 12–31%) of infections in 10- to 19-year-olds, rising to 69% (57–82%) of infections in people aged over 70 years. Accordingly, we find that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low. Our age-specific clinical fraction and susceptibility estimates have implications for the expected global burden of COVID-19, as a result of demographic differences across settings. In countries with younger population structures—such as many low-income countries—the expected per capita incidence of clinical cases would be lower than in countries with older population structures, although it is likely that comorbidities in low-income countries will also influence disease severity. Without effective control measures, regions with relatively older populations could see disproportionally more cases of COVID-19, particularly in the later stages of an unmitigated epidemic. A new epidemiological study shows reduced susceptibility to SARS-CoV-2 and decreased risk of developing severe symptoms in people aged younger than 20 years, suggesting that children have limited contribution to spread of COVID-19.

1,281 citations

Journal ArticleDOI
TL;DR: Estimates of mixing patterns for societies for which contact data such as POLYMOD are not yet available are provided, finding contact patterns are highly assortative with age across all countries considered, but pronounced regional differences in the age-specific contacts at home were noticeable.
Abstract: Heterogeneities in contact networks have a major effect in determining whether a pathogen can become epidemic or persist at endemic levels. Epidemic models that determine which interventions can successfully prevent an outbreak need to account for social structure and mixing patterns. Contact patterns vary across age and locations (e.g. home, work, and school), and including them as predictors in transmission dynamic models of pathogens that spread socially will improve the models' realism. Data from population-based contact diaries in eight European countries from the POLYMOD study were projected to 144 other countries using a Bayesian hierarchical model that estimated the proclivity of age-and-location-specific contact patterns for the countries, using Markov chain Monte Carlo simulation. Household level data from the Demographic and Health Surveys for nine lower-income countries and socio-demographic factors from several on-line databases for 152 countries were used to quantify similarity of countries to estimate contact patterns in the home, work, school and other locations for countries for which no contact data are available, accounting for demographic structure, household structure where known, and a variety of metrics including workforce participation and school enrolment. Contacts are highly assortative with age across all countries considered, but pronounced regional differences in the age-specific contacts at home were noticeable, with more inter-generational contacts in Asian countries than in other settings. Moreover, there were variations in contact patterns by location, with work-place contacts being least assortative. These variations led to differences in the effect of social distancing measures in an age structured epidemic model. Contacts have an important role in transmission dynamic models that use contact rates to characterize the spread of contact-transmissible diseases. This study provides estimates of mixing patterns for societies for which contact data such as POLYMOD are not yet available.

734 citations

Journal ArticleDOI
19 Feb 2021-Science
TL;DR: The results indicate that, by using effective interventions, some countries could control the epidemic while avoiding stay-at-home orders, and this model accounts for uncertainty in key epidemiological parameters, such as the average delay from infection to death.
Abstract: Governments are attempting to control the COVID-19 pandemic with nonpharmaceutical interventions (NPIs). However, the effectiveness of different NPIs at reducing transmission is poorly understood. We gathered chronological data on the implementation of NPIs for several European, and other, countries between January and the end of May 2020. We estimate the effectiveness of NPIs, ranging from limiting gathering sizes, business closures, and closure of educational institutions to stay-at-home orders. To do so, we used a Bayesian hierarchical model that links NPI implementation dates to national case and death counts and supported the results with extensive empirical validation. Closing all educational institutions, limiting gatherings to 10 people or less, and closing face-to-face businesses each reduced transmission considerably. The additional effect of stay-at-home orders was comparatively small.

674 citations

Posted ContentDOI
27 Mar 2020-medRxiv
TL;DR: It is found that interventions aimed at children may have a relatively small impact on total cases, particularly if the transmissibility of subclinical infections is low, and the expected clinical attack rate would be lower in younger populations than in older populations.
Abstract: The COVID-19 pandemic has shown a markedly low proportion of cases among children. Age disparities in observed cases could be explained by assortative mixing patterns and reactive school closures which decrease mixing between children, or by children exhibiting lower susceptibility to infection, or by children having a lower propensity to show clinical symptoms. We formally test these hypotheses by fitting an age-structured mathematical model to epidemic data from six countries, finding strong age dependence in the probability of developing clinical symptoms, rising from around 20% in under 10s to over 70% in older adults. We find that interventions aimed at halting transmission in children may have minimal effects on preventing cases depending on the relative transmissibility of subclinical infections. Our estimated age-specific clinical fraction has implications for the expected global burden of clinical cases because of demographic differences across settings. In younger populations, the expected clinical attack rate would be lower, although it is likely that comorbidities in low-income countries will affect disease severity. Without effective control measures, regions with older populations may see disproportionally more clinical cases, particularly in the later stages of the pandemic.

645 citations


Additional excerpts

  • ...7-24) Middle 43 (32-55) Old 70 (61-79) Young 14 (11-18) Middle 55 (49-60) Old 64 (60-68)...

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References
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BookDOI
TL;DR: The Markov Chain Monte Carlo Implementation Results Summary and Discussion MEDICAL MONITORING Introduction Modelling Medical Monitoring Computing Posterior Distributions Forecasting Model Criticism Illustrative Application Discussion MCMC for NONLINEAR HIERARCHICAL MODELS.
Abstract: INTRODUCING MARKOV CHAIN MONTE CARLO Introduction The Problem Markov Chain Monte Carlo Implementation Discussion HEPATITIS B: A CASE STUDY IN MCMC METHODS Introduction Hepatitis B Immunization Modelling Fitting a Model Using Gibbs Sampling Model Elaboration Conclusion MARKOV CHAIN CONCEPTS RELATED TO SAMPLING ALGORITHMS Markov Chains Rates of Convergence Estimation The Gibbs Sampler and Metropolis-Hastings Algorithm INTRODUCTION TO GENERAL STATE-SPACE MARKOV CHAIN THEORY Introduction Notation and Definitions Irreducibility, Recurrence, and Convergence Harris Recurrence Mixing Rates and Central Limit Theorems Regeneration Discussion FULL CONDITIONAL DISTRIBUTIONS Introduction Deriving Full Conditional Distributions Sampling from Full Conditional Distributions Discussion STRATEGIES FOR IMPROVING MCMC Introduction Reparameterization Random and Adaptive Direction Sampling Modifying the Stationary Distribution Methods Based on Continuous-Time Processes Discussion IMPLEMENTING MCMC Introduction Determining the Number of Iterations Software and Implementation Output Analysis Generic Metropolis Algorithms Discussion INFERENCE AND MONITORING CONVERGENCE Difficulties in Inference from Markov Chain Simulation The Risk of Undiagnosed Slow Convergence Multiple Sequences and Overdispersed Starting Points Monitoring Convergence Using Simulation Output Output Analysis for Inference Output Analysis for Improving Efficiency MODEL DETERMINATION USING SAMPLING-BASED METHODS Introduction Classical Approaches The Bayesian Perspective and the Bayes Factor Alternative Predictive Distributions How to Use Predictive Distributions Computational Issues An Example Discussion HYPOTHESIS TESTING AND MODEL SELECTION Introduction Uses of Bayes Factors Marginal Likelihood Estimation by Importance Sampling Marginal Likelihood Estimation Using Maximum Likelihood Application: How Many Components in a Mixture? Discussion Appendix: S-PLUS Code for the Laplace-Metropolis Estimator MODEL CHECKING AND MODEL IMPROVEMENT Introduction Model Checking Using Posterior Predictive Simulation Model Improvement via Expansion Example: Hierarchical Mixture Modelling of Reaction Times STOCHASTIC SEARCH VARIABLE SELECTION Introduction A Hierarchical Bayesian Model for Variable Selection Searching the Posterior by Gibbs Sampling Extensions Constructing Stock Portfolios With SSVS Discussion BAYESIAN MODEL COMPARISON VIA JUMP DIFFUSIONS Introduction Model Choice Jump-Diffusion Sampling Mixture Deconvolution Object Recognition Variable Selection Change-Point Identification Conclusions ESTIMATION AND OPTIMIZATION OF FUNCTIONS Non-Bayesian Applications of MCMC Monte Carlo Optimization Monte Carlo Likelihood Analysis Normalizing-Constant Families Missing Data Decision Theory Which Sampling Distribution? Importance Sampling Discussion STOCHASTIC EM: METHOD AND APPLICATION Introduction The EM Algorithm The Stochastic EM Algorithm Examples GENERALIZED LINEAR MIXED MODELS Introduction Generalized Linear Models (GLMs) Bayesian Estimation of GLMs Gibbs Sampling for GLMs Generalized Linear Mixed Models (GLMMs) Specification of Random-Effect Distributions Hyperpriors and the Estimation of Hyperparameters Some Examples Discussion HIERARCHICAL LONGITUDINAL MODELLING Introduction Clinical Background Model Detail and MCMC Implementation Results Summary and Discussion MEDICAL MONITORING Introduction Modelling Medical Monitoring Computing Posterior Distributions Forecasting Model Criticism Illustrative Application Discussion MCMC FOR NONLINEAR HIERARCHICAL MODELS Introduction Implementing MCMC Comparison of Strategies A Case Study from Pharmacokinetics-Pharmacodynamics Extensions and Discussion BAYESIAN MAPPING OF DISEASE Introduction Hypotheses and Notation Maximum Likelihood Estimation of Relative Risks Hierarchical Bayesian Model of Relative Risks Empirical Bayes Estimation of Relative Risks Fully Bayesian Estimation of Relative Risks Discussion MCMC IN IMAGE ANALYSIS Introduction The Relevance of MCMC to Image Analysis Image Models at Different Levels Methodological Innovations in MCMC Stimulated by Imaging Discussion MEASUREMENT ERROR Introduction Conditional-Independence Modelling Illustrative examples Discussion GIBBS SAMPLING METHODS IN GENETICS Introduction Standard Methods in Genetics Gibbs Sampling Approaches MCMC Maximum Likelihood Application to a Family Study of Breast Cancer Conclusions MIXTURES OF DISTRIBUTIONS: INFERENCE AND ESTIMATION Introduction The Missing Data Structure Gibbs Sampling Implementation Convergence of the Algorithm Testing for Mixtures Infinite Mixtures and Other Extensions AN ARCHAEOLOGICAL EXAMPLE: RADIOCARBON DATING Introduction Background to Radiocarbon Dating Archaeological Problems and Questions Illustrative Examples Discussion Index

7,399 citations

BookDOI
01 Jan 2001
TL;DR: This book presents the first comprehensive treatment of Monte Carlo techniques, including convergence results and applications to tracking, guidance, automated target recognition, aircraft navigation, robot navigation, econometrics, financial modeling, neural networks, optimal control, optimal filtering, communications, reinforcement learning, signal enhancement, model averaging and selection.
Abstract: Monte Carlo methods are revolutionizing the on-line analysis of data in fields as diverse as financial modeling, target tracking and computer vision. These methods, appearing under the names of bootstrap filters, condensation, optimal Monte Carlo filters, particle filters and survival of the fittest, have made it possible to solve numerically many complex, non-standard problems that were previously intractable. This book presents the first comprehensive treatment of these techniques, including convergence results and applications to tracking, guidance, automated target recognition, aircraft navigation, robot navigation, econometrics, financial modeling, neural networks, optimal control, optimal filtering, communications, reinforcement learning, signal enhancement, model averaging and selection, computer vision, semiconductor design, population biology, dynamic Bayesian networks, and time series analysis. This will be of great value to students, researchers and practitioners, who have some basic knowledge of probability. Arnaud Doucet received the Ph. D. degree from the University of Paris-XI Orsay in 1997. From 1998 to 2000, he conducted research at the Signal Processing Group of Cambridge University, UK. He is currently an assistant professor at the Department of Electrical Engineering of Melbourne University, Australia. His research interests include Bayesian statistics, dynamic models and Monte Carlo methods. Nando de Freitas obtained a Ph.D. degree in information engineering from Cambridge University in 1999. He is presently a research associate with the artificial intelligence group of the University of California at Berkeley. His main research interests are in Bayesian statistics and the application of on-line and batch Monte Carlo methods to machine learning. Neil Gordon obtained a Ph.D. in Statistics from Imperial College, University of London in 1993. He is with the Pattern and Information Processing group at the Defence Evaluation and Research Agency in the United Kingdom. His research interests are in time series, statistical data analysis, and pattern recognition with a particular emphasis on target tracking and missile guidance.

6,574 citations

Book
01 Jan 2001
TL;DR: This book provides a self-contained and up-to-date treatment of the Monte Carlo method and develops a common framework under which various Monte Carlo techniques can be "standardized" and compared.
Abstract: This paperback edition is a reprint of the 2001 Springer edition. This book provides a self-contained and up-to-date treatment of the Monte Carlo method and develops a common framework under which various Monte Carlo techniques can be "standardized" and compared. Given the interdisciplinary nature of the topics and a moderate prerequisite for the reader, this book should be of interest to a broad audience of quantitative researchers such as computational biologists, computer scientists, econometricians, engineers, probabilists, and statisticians. It can also be used as the textbook for a graduate-level course on Monte Carlo methods. Many problems discussed in the alter chapters can be potential thesis topics for masters or Ph.D. students in statistics or computer science departments. Jun Liu is Professor of Statistics at Harvard University, with a courtesy Professor appointment at Harvard Biostatistics Department. Professor Liu was the recipient of the 2002 COPSS Presidents' Award, the most prestigious one for statisticians and given annually by five leading statistical associations to one individual under age 40. He was selected as a Terman Fellow by Stanford University in 1995, as a Medallion Lecturer by the Institute of Mathematical Statistics (IMS) in 2002, and as a Bernoulli Lecturer by the International Bernoulli Society in 2004. He was elected to the IMS Fellow in 2004 and Fellow of the American Statistical Association in 2005. He and co-workers have published more than 130 research articles and book chapters on Bayesian modeling and computation, bioinformatics, genetics, signal processing, stochastic dynamic systems, Monte Carlo methods, and theoretical statistics. "An excellent survey of current Monte Carlo methods. The applications amply demonstrate the relevance of this approach to modern computing. The book is highly recommended." (Mathematical Reviews) "This book provides comprehensive coverage of Monte Carlo methods, and in the process uncovers and discusses commonalities among seemingly disparate techniques that arose in various areas of application. The book is well organized; the flow of topics follows a logical development. The coverage is up-to-date and comprehensive, and so the book is a good resource for people conducting research on Monte Carlo methods. The book would be an excellent supplementary text for a course in scientific computing ." (SIAM Review) "The strength of this book is in bringing together advanced Monte Carlo (MC) methods developed in many disciplines. Throughout the book are examples of techniques invented, or reinvented, in different fields that may be applied elsewhere. Those interested in using MC to solve difficult problems will find many ideas, collected from a variety of disciplines, and references for further study." (Technometrics)

2,973 citations

Journal ArticleDOI
27 Jul 2006-Nature
TL;DR: It is found that border restrictions and/or internal travel restrictions are unlikely to delay spread by more than 2–3 weeks unless more than 99% effective, and vaccine stockpiled in advance of a pandemic could significantly reduce attack rates even if of low efficacy.
Abstract: Development of strategies for mitigating the severity of a new influenza pandemic is now a top global public health priority. Influenza prevention and containment strategies can be considered under the broad categories of antiviral, vaccine and non-pharmaceutical (case isolation, household quarantine, school or workplace closure, restrictions on travel) measures. Mathematical models are powerful tools for exploring this complex landscape of intervention strategies and quantifying the potential costs and benefits of different options. Here we use a large-scale epidemic simulation to examine intervention options should initial containment of a novel influenza outbreak fail, using Great Britain and the United States as examples. We find that border restrictions and/or internal travel restrictions are unlikely to delay spread by more than 2-3 weeks unless more than 99% effective. School closure during the peak of a pandemic can reduce peak attack rates by up to 40%, but has little impact on overall attack rates, whereas case isolation or household quarantine could have a significant impact, if feasible. Treatment of clinical cases can reduce transmission, but only if antivirals are given within a day of symptoms starting. Given enough drugs for 50% of the population, household-based prophylaxis coupled with reactive school closure could reduce clinical attack rates by 40-50%. More widespread prophylaxis would be even more logistically challenging but might reduce attack rates by over 75%. Vaccine stockpiled in advance of a pandemic could significantly reduce attack rates even if of low efficacy. Estimates of policy effectiveness will change if the characteristics of a future pandemic strain differ substantially from those seen in past pandemics.

2,099 citations


"Estimating the impact of school clo..." refers background in this paper

  • ...The second term is the sampling density for the complete history Z of the epidemic (equation (1))....

    [...]

  • ...Irrespective of {dcom, dhous}, we find that accounting for holidays improves the model fit: (1) log-likelihoods are larger (see Supplementary Information); (2) child RPE becomes close to 0% during holidays (Fig....

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Journal ArticleDOI
TL;DR: The strength of this book is in bringing together advanced Monte Carlo methods developed in many disciplines, including the Ising model, molecular structure simulation, bioinformatics, target tracking, hypothesis testing for astronomical observations, Bayesian inference of multilevel models, missing-data problems.
Abstract: (2002). Monte Carlo Strategies in Scientific Computing. Technometrics: Vol. 44, No. 4, pp. 403-404.

1,434 citations