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

Joel Hellewell, Sam Abbott, Amy Gimma, Nikos I Bosse, Christopher I Jarvis, Timothy W Russell, James D Munday, Adam J Kucharski, W John Edmunds, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Sebastian Funk, Rosalind M Eggo, Fiona Sun, Stefan Flasche, Billy J Quilty, Nicholas Davies, Yang Liu, Samuel Clifford, Petra Klepac, Mark Jit, Charlie Diamond, Hamish Gibbs, Kevin van Zandvoort, Joel Hellewell, Sam Abbott, Amy Gimma, Nikos I Bosse, Christopher I Jarvis, Timothy W Russell, James D Munday, Adam J Kucharski, W John Edmunds, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Sebastian Funk, Rosalind M Eggo, Fiona Sun, Stefan Flasche, Billy J Quilty, Nicholas Davies, Yang Liu, Samuel Clifford, Petra Klepac, Mark Jit, Charlie Diamond, Hamish Gibbs, Kevin van Zandvoort

Abstract

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 (R0), 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 R0 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 R0 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 R0 of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2·5 more than 70% of contacts had to be traced, and for an R0 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 R0 was 1·5. For R0 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.

Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Example of the simulated process that starts with person A being infected After an incubation period, person A shows symptoms and is isolated at a time drawn from the delay distribution (table). A draw from the negative binomial distribution with mean reproduction number (R0) and distribution parameter determines how many people person A potentially infects. For each of those, a serial interval is drawn. Two of these exposures occur before the time person A is isolated. Each contact is traced with probability ρ, with probability 1–ρ they are missed by contact tracing. Person B is successfully traced, which means that they will be isolated without delay when they develop symptoms. They could, however, still infect others before they are isolated. Person C is missed by contact tracing. This means that they are only detected if and when symptomatic, and are isolated after a delay from symptom onset. Because person C was not traced, they infected two more people (E and F), in addition to person D, than if they had been isolated at symptom onset. A version with subclinical transmission is given in the appendix appendix (p 12).
Figure 2
Figure 2
Probability distributions used in simulations (A) The short and long delay distributions between the onset of symptoms and isolation (median marked by line). Parameter values and references are given in the table. (B) The incubation distribution estimate fitted to data from the Wuhan outbreak by Backer and colleagues. (C) An example of the method used to sample the serial interval for a case that has an incubation period of 5 days. Each case has an incubation period drawn from the distribution in (B), their serial interval is then drawn from a skewed normal distribution with the mean set to the incubation period of the case. In (C), the incubation period was 5 days. The skew parameter of the skewed normal distribution controls the proportion of transmission that occurs before symptom onset; the three scenarios explored are less than 1%, 15%, and 30% of transmission before onset.
Figure 3
Figure 3
Effect of isolation and contact tracing on controlling outbreaks and on the effective reproduction number (A) The percentage of outbreaks that are controlled for scenarios with varying reproduction number (R0), at each value of contacts traced. The baseline scenario is R0 of 2·5, 20 initial cases, a short delay to isolation, 15% of transmission before symptom onset, and 0% subclinical infection. A simulated outbreak is defined as controlled if there are no cases between weeks 12 and 16 after the initial cases. Other scenarios are presented in the appendix (p 2). (B) Effective reproduction number in the presence of case isolation and contact tracing. Median, and 50% and 95% intervals are shown.
Figure 4
Figure 4
Achieving control of simulated outbreaks under different transmission scenarios The percentage of outbreaks controlled for the baseline scenario, and varied number of initial cases (A), time from onset to isolation (B), percentage of transmission before symptoms (C), and proportion of subclinical (asymptomatic) cases (D). The baseline scenario is a basic reproduction number (R0) of 2·5, 20 initial cases, a short delay to isolation, 15% of transmission before symptom onset, and 0% subclinical infection. Results for R0=1·5 and 3·5 are given in the appendix. A simulated outbreak is defined as controlled if there are no cases between weeks 12 and 16 after the initial cases.
Figure 5
Figure 5
The maximum weekly cases requiring contact tracing and isolation in scenarios with 20 index cases that achieved control within 3 months Scenarios vary by reproduction number and the mean delay from onset to isolation. 15% of transmission occurred before symptom onset, and 0% subclinical infection. The percentage of simulations that achieved control is shown in the boxplot. This illustrates the potential size of the eventually controlled simulated outbreaks, which would need to be managed through contact tracing and isolation. *The interval extends out of the plotting region.

References

    1. WHO . World Health Organization; 2020. Novel coronavirus (2019-nCoV) situation report 16.
    1. WHO . World Health Organization; 2020. Novel coronavirus (2019-nCoV) situation report 2.
    1. European Centre for Disease Prevention and Control . European Centre for Disease Prevention and Control; 2020. Public health management of persons having had contact with novel coronavirus cases in the European Union.
    1. Quilty B, Clifford S, CCMID nCoV working group. Flasche S, Eggo RM. Effectiveness of airport screening at detecting travellers infected with 2019-nCoV. 2020.
    1. Fraser C, Riley S, Anderson RM, Ferguson NM. Factors that make an infectious disease outbreak controllable. Proc Natl Acad Sci USA. 2004;101:6146–6151.
    1. Peak CM, Childs LM, Grad YH, Buckee CO. Comparing nonpharmaceutical interventions for containing emerging epidemics. Proc Natl Acad Sci USA. 2017;114:4023–4028.
    1. Glasser JW, Hupert N, McCauley MM, Hatchett R. Modeling and public health emergency responses: lessons from SARS. Epidemics. 2011;3:32–37.
    1. Swanson KC, Altare C, Wesseh CS, et al. Contact tracing performance during the Ebola epidemic in Liberia, 2014–2015. PLoS Negl Trop Dis. 2018;12
    1. WHO . World Health Organization; 2015. Implementation and management of contact tracing for Ebola virus disease.
    1. Kang M, Song T, Zhong H, et al. Contact tracing for imported case of Middle East respiratory syndrome, China, 2015. Emerging Infect Dis. 2016;22:9.
    1. Public Health England MERS-CoV close contact algorithm. Public health investigation and management of close contacts of Middle East Respiratory Coronavirus (MERS-CoV) cases (v17 29 January 2019) 2019.
    1. European Centre for Disease Prevention and Control Risk assessment guidelines for diseases transmitted on aircraft. Part 2: Operational guidelines for assisting in the evaluation of risk for transmission by disease. 2011.
    1. Hoang TTT, Nguyen VN, Dinh NS, et al. Active contact tracing beyond the household in multidrug resistant tuberculosis in Vietnam: a cohort study. BMC Public Health. 2019;19:241.
    1. Klinkenberg D, Fraser C, Heesterbeek H. The effectiveness of contact tracing in emerging epidemics. PLoS One. 2006;1:e12.
    1. Abbott S, Hellewell J, Munday J, CMMID nCoV working group. Funk S. The transmissibility of novel coronavirus in the early stages of the 2019–20 outbreak in Wuhan: exploring initial point-source exposure sizes and durations using scenario analysis. Wellcome Open Res. 2020;5:17.
    1. Imai N, Cori A, Dorigatti I, et al. Report 3: transmissibility of 2019-nCov. 2020.
    1. Kucharski AJ, Eggo RM, Watson CH, Camacho A, Funk S, Edmunds WJ. Effectiveness of ring vaccination as control strategy for Ebola virus disease. Emerg Infect Dis. 2016;22:105–108.
    1. Imai N, Dorigatti I, Cori A, Riley S, Ferguson NM. Estimating the potential total number of novel coronavirus cases in Wuhan City, China. 2020.
    1. Lloyd-Smith JO, Schreiber SJ, Kopp PE, Getz WM. Superspreading and the effect of individual variation on disease emergence. Nature. 2005;438:355–359.
    1. Donnelly CA, Ghani AC, Leung GM, et al. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet. 2003;361:1761–1766.
    1. Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020 doi: 10.1056/NEJMoa2001316. published online Jan 29.
    1. Backer JA, Klinkenberg D, Wallinga J. The incubation period of 2019-nCoV infections among travellers from Wuhan, China. medRxiv. 2020 doi: 10.1101/2020.01.27.20018986. published online Jan 28. (preprint).
    1. BBC News Coronavirus patient is University of York student. Feb 1, 2020.
    1. Riou J, Althaus CL. Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020. Eurosurveillance. 2020;25
    1. Bedford T, Neher R, Hadfield J, Hodcroft E, Ilcisin M, Müller N. Genomic analysis of nCoV spread. Situation report 2020-01-30. 2020.
    1. Majumder M, Mandl KD. Social Science Research Network; Rochester, NY: 2020. Early transmissibility assessment of a novel coronavirus in Wuhan, China.
    1. Read JM, Bridgen JR, Cummings DA, Ho A, Jewell CP. Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions. medRxiv. 2020 doi: 10.1101/2020.01.23.20018549. published online Jan 28. (preprint).
    1. Zhao S, Ran J, Musa SS, et al. Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: a data-driven analysis in the early phase of the outbreak. Int J Infect Dis. 2020;92:214–217.
    1. Dugas AF, Jalalpour M, Gel Y, et al. Influenza forecasting with Google Flu Trends. PLoS One. 2013;8
    1. Yu P, Zhu J, Zhang Z, Han Y, Huang L. A familial cluster of infection associated with the 2019 novel coronavirus indicating potential person-to-person transmission during the incubation period. J Infect Dis. 2020 doi: 10.1093/infdis/jiaa077. published online Feb 18.
    1. Heymann DL, Shindo N. COVID-19: what is next for public health? Lancet. 2020;395:542–545.
    1. Dhillon RS, Srikrishna D. When is contact tracing not enough to stop an outbreak? Lancet Infect Dis. 2018;18:1302–1304.
    1. Olu OO, Lamunu M, Nanyunja M, et al. Contact tracing during an outbreak of Ebola virus disease in the Western area districts of Sierra Leone: lessons for future Ebola outbreak response. Front Public Health. 2016;4:130.
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. Pang X, Zhu Z, Xu F, et al. Evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in Beijing, 2003. JAMA. 2003;290:3215–3221.

Source: PubMed

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