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      Testing, tracing and isolation in compartmental models

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          Abstract

          Existing compartmental mathematical modelling methods for epidemics, such as SEIR models, cannot accurately represent effects of contact tracing. This makes them inappropriate for evaluating testing and contact tracing strategies to contain an outbreak. An alternative used in practice is the application of agent- or individual-based models (ABM). However ABMs are complex, less well-understood and much more computationally expensive. This paper presents a new method for accurately including the effects of Testing, contact-Tracing and Isolation (TTI) strategies in standard compartmental models. We derive our method using a careful probabilistic argument to show how contact tracing at the individual level is reflected in aggregate on the population level. We show that the resultant SEIR-TTI model accurately approximates the behaviour of a mechanistic agent-based model at far less computational cost. The computational efficiency is such that it can be easily and cheaply used for exploratory modelling to quantify the required levels of testing and tracing, alone and with other interventions, to assist adaptive planning for managing disease outbreaks.

          Author summary

          The importance of modeling to inform and support decision making is widely acknowledged. Understanding how to enhance contact tracing as part of the Testing-Tracing-Isolation (TTI) strategy for mitigation of COVID is a key public policy questions. Our work develops the SEIR-TTI model as an extension of the classic Susceptible, Exposed, Infected and Recovered (SEIR) model to include tracing of contacts of people exposed to and infectious with COVID-19. We use probabilistic argument to derive contact tracing rates within a compartmental model as aggregates of contact tracing at an individual level. Our adaptation is applicable across compartmental models for infectious diseases spread. We show that our novel SEIR-TTI model can accurately approximate the behaviour of mechanistic agent-based models at far less computational cost. The SEIR-TTI model represents an important addition to the theoretical methodology of modelling infectious disease spread and we anticipate that it will be immediately applicable to the management of the COVID-19 pandemic.

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          Most cited references88

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          Temporal dynamics in viral shedding and transmissibility of COVID-19

          We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.
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            A Contribution to the Mathematical Theory of Epidemics

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              Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts

              Summary Background Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. Methods We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R 0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. Findings Simulated outbreaks starting with five initial cases, an R 0 of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R 0 was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R 0 of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R 0 of 2·5 more than 70% of contacts had to be traced, and for an R 0 of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R 0 was 1·5. For R 0 values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. Interpretation In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. Funding Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Comput Biol
                PLoS Comput Biol
                plos
                ploscomp
                PLoS Computational Biology
                Public Library of Science (San Francisco, CA USA )
                1553-734X
                1553-7358
                March 2021
                4 March 2021
                : 17
                : 3
                : e1008633
                Affiliations
                [1 ] Scientific Computing Department, UKRI, Rutherford Appleton Laboratory, Harwell, United Kingdom
                [2 ] School of Informatics, University of Edinburgh, Edinburgh, United Kingdom
                [3 ] UCL Institute for Global Health, London, United Kingdom
                [4 ] University of Haifa Health and Risk Communication Research Center, Haifa, Israel
                [5 ] Department of Applied Health Research, UCL, London, United Kingdom
                [6 ] Wolfson Centre for Mathematical Biology and The Queen’s College, Oxford University, Oxford, United Kingdom
                ETH Zurich, SWITZERLAND
                Author notes

                The authors have declared that no competing interests exist.

                [¤]

                Current address: Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, UK is current address for W.Waites

                Author information
                https://orcid.org/0000-0003-4851-1144
                https://orcid.org/0000-0002-7759-6805
                https://orcid.org/0000-0002-6917-6552
                https://orcid.org/0000-0001-8599-8380
                https://orcid.org/0000-0002-7720-1121
                Article
                PCOMPBIOL-D-20-00860
                10.1371/journal.pcbi.1008633
                7932151
                33661888
                f161b425-2387-4644-a359-9c95fb4ba7b3
                © 2021 Sturniolo 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.

                History
                : 20 May 2020
                : 14 December 2020
                Page count
                Figures: 9, Tables: 1, Pages: 28
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100014589, Chief Scientist Office, Scottish Government Health and Social Care Directorate;
                Award ID: COV/EDI/20/12
                Award Recipient :
                Funded by: NIHR ARC North Thames
                Award Recipient :
                WW was supported by the Chief Scientist Office Scotland (COV/EDI/20/12). JPG was supported by the National Institute for Health Research (NIHR) Applied Health Research and Care North Thames at Bart’s Health NHS Trust (NIHR ARC North Thames). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.
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                Data underlying the findings are available at https://github.com/ptti/ptti/tree/ptti-theory-paper.

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