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Modeling the SARS epidemic in Hong Kong Dr. Liu Hongjie, Prof. Wong Tze Wai Department of Community & Family Medicine The Chinese University of Hong Kong Dr. James Derrick Department of Anaesthesia & Intensive Care Prince of Wales Hospital May 13, 2003 Modeling the SARS epidemic in Hong Kong • We aim to construct a model of the SARS epidemic in community (i.e., we have excluded the outbreaks among health care workers or the “common source” outbreak in Amoy Garden. • The model only applies to a person-toperson mode of transmission of SARS. Objectives of the Media Release: 1. Explain the natural course of an epidemic – the relationship between the population that is infectious (including patients and infected individuals who will become patients), susceptible population and immune (recovered) population; 2. Show how the natural progression of an epidemic is affected by the effectiveness and timeliness of public health measures, by introducing our mathematical model; 3. Using the assumptions and limitations of our model, discuss the current situation in terms of the trend of the epidemic and the likelihood of its resurgence; Dynamics of disease and of infectiousness at the individual level Dynamics of disease Time of infection Susceptible Susceptible Clinical onset Incubation period Latent period Resolution Symptomatic period • immune • carrier Relapse • dead • recovered infectious period Onset of infectiousness Dynamics of infectiousness End of infectiousness Times (days) Dynamics of infectiousness at the population level Susceptible St Infectious It Recovered / immune Rt SIR Basic Reproductive Number (R0) • The average number of individuals directly infected by an infectious case during his/her entire infectious period • In a population if R0 > 1 : epidemic if R0 = 1 : endemic stage if R0 < 1 : sucessful control of infection • If population is completely susceptible measles : R0 = 15-20 smallpox : R0 = 3 – 5 SARS: ??? Basic (R0) reproductive number R0 = Number of contact per day x Transmission probability per contact x Duration of infectiousness = D • Average number of contacts made by an infective individual during the infectious period: D e.g. 2 persons per day X 5 days = 10 persons • Number of new infections produced by one infective during his infectious period: No. of contacts during D ( D ) X transmission probability per contact ( ) e.g. 10 persons X 0.2 = 2 infected cases Basic (R0) reproductive number R0 = Number of contact per day x Transmission probability per contact x Duration of infectiousness = D Preventive measures targeting reducing any parts of the components will halt SARS epidemic SIR Model Susceptible St Infectious It Recovered / immune Rt SIR St: Proportion of population (n) that is susceptible at time t It: Proportion of n that is currently infected and infectious at time t Rt : Proportion of n that is recovered / immune SIR mode is used to predict the three proportions at different scenarios. Estimate of the 3 proportions changing over time t Susceptible St Infectious It Recovered / immune Rt Time derivatives of 3 proportion dX/dt, where X could be S, I or R At any time t during the epidemic, the 3 equations will be: dS/dt = - S I dI/dt = SI – I/D dR/dt = I/D SIR A close look at dS/dt = - S I Susceptible St Infectious It Recovered / immune Rt In population, there are 6 different types of possible contacts Susceptible meets susceptible (S - S, no transmission) Susceptible meets infectious (S - I, transmission) Susceptible meets resistant (immune) (S - R, no transmission) Infectious meets infectious (I - I, no transmission) Infectious meets resistant (I - R, no transmission) Resistant meets resistant (R - R, no transmission) SIR Assumptions of this model 1. the average household size is 3 (census data in 2001); 2. the interval between onset of disease and admission to hospitals is 5 days (based on the paper by Peiris et al. Coronavirus as a possible cause of SARS. Lancet online, 8 April, 2003); 3. Once SARS patients are hospitalized, they are not able to disseminate the infection back to the community; 4. Patients are infectious one day before the onset of their illness till hospitalized. Guideline for estimate R0 R0 Mean life expectancy / Average age at infection In Hong Kong, the mean life expectancy is about 80 years. The average age at the SARS infection is about 40, thus R0 80 / 40 2 The value of R0 is used to estimate the parameters in modeling the natural history of the SARS epidemic in Hong Kong. (Ref. Anderson and May. Infectious Diseases of Humans: Dynamics and Control, 1991) Estimate of parameters----- Natural history • Duration of infectivity (day): 6 days 1 day before onset of symptoms 5 day-delay in seeking treatment (Peiris’s paper) • : No. of contacted person: 14 Household (HH): 2 (Average household size is 3 according HK censes in 2001) Social contacts (SC): 12 No. of contacted persons / day: 14/6 = 2.33 • : Risk of transmission per contact HH: 0.25 SC: 0.1 Weighted average : 0.149995 • Two infectious cases enter the susceptible population Proportions of S, I and R Natural history of SARS epidemic 1 0.9 Susceptible 0.8 S I Recovered/Immune 0.6 R 0.5 0.4 0.3 0.2 0.1 Infectious Days of epidemic 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 0 Proportion 0.7 Proportions of infectious population (Control started on different dates) 0.2 Natural 0.18 0.16 Ro= 2.01 0.12 0.1 Day 20 0.08 Day 30 Day 10 0.06 Day 40 0.04 Ro= 1.44 0.02 Days of epidemic 348 336 324 312 300 288 276 264 252 240 228 216 204 192 180 168 156 144 132 120 108 96 84 72 60 48 36 24 12 0 0 Proportion 0.14 Proportions of infectious population at different Ro 0.2 Ro = 2.01 0.18 0.16 0.12 0.1 0.08 Ro = 1.44 0.06 Ro = 1.39 0.04 Ro = 1.3 0.02 Control started on day 10 Ro = 1.17 Days of epidemic 348 336 324 312 300 288 276 264 252 240 228 216 204 192 180 168 156 144 132 120 108 96 84 72 60 48 36 24 12 0 0 Proportion 0.14 Predicted number of SARS infectious cases 180 Control Stage 1 starting from on day 20: = 0.144, = 2, D = 5, Ro= 1.44 160 Control Stage 2 starting from on day 30: = 0.14, = 2, D = 3, Ro= 0.84 120 100 80 60 40 20 Days of epidemic 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 0 Infectious cases 140 Proportions of S, I and R on log scale (Control at two stages) 95 10 0 10 5 11 0 11 5 12 0 12 5 13 0 13 5 14 0 85 90 75 80 65 70 55 60 45 50 35 40 25 30 15 20 5 10 0 1 0.1 Susceptible S Proportion on log scale 0.01 I 0.001 Recovered/Immune R 0.0001 0.00001 Infectious 0.000001 0.0000001 0.00000001 Days of epidemic Computer Assisted SARS Modeling Main Messages to bring across 1. If the epidemic is allowed “to run its natural course”, in other words, to die down by itself, up to several million people will fall victim to SARS. Sufficient herd immunity that will protect the community from further epidemics will only be achieved at the expense of this magnitude of community infection; 2. An epidemic will die down only when the basic reproductive number, Ro (number of people infected by a patient) is less than one. This can be achieved only in two ways:- when herd immunity is high enough (natural course of events), or when effective public health measures limit the spread of the epidemic; Main Messages to bring across: 3. At present, with all the public health measures in place, it appears our public health measures are capable to reduce the number (Ro) to <1; 4. To effectively control the epidemic, efforts must be sustained keep Ro to <1. Otherwise, the epidemic can start again at any time, because the proportion of immune individuals in our population (herd immunity) is far too low to offer any “natural protection”.