Detection of infectious disease outbreak by an optimal Bayesian alarm system



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Detection of infectious disease outbreak by an optimal Bayesian alarm system Antónia Turkman, Valeska Andreozzi, Sandra Ramos, Marília Antunes and Feridun Turkman Centre of Statistics and Applications of Lisbon University METMAVI International Workshop on Spatio-Temporal Modelling Guimarães, Portugal September 2012

Outline of the talk Background Objective Methods 1. Construction of warning systems 2. Event prediction and screening Application Discussion 2 of 28

3 of 28 Background

Introduction Let {Y t } be a time series (e.g. the number of dengue cases at time t monthly, weekly or otherwise). The interest lies in predicting whether the process will upcross a fixed level u at time t + h: Y t+l 1 < u Y t+l 4 of 28

Introduction Let {Y t } be a time series (e.g. the number of dengue cases at time t monthly, weekly or otherwise). The interest lies in predicting whether the process will upcross a fixed level u at time t + h: Y t+l 1 < u Y t+l A naive way to proceed is to foretell at time t that Y t+l will upcross u if a point predictor, Ŷt+l,t, say upcrosses some level û. Ŷ t+l,t = E [Y t+l Y s, < s t, l > 0], Since V (Ŷt+l,t) < V (Y t+l,t ) it is reasonable to take û < u. 4 of 28

Introduction Let {Y t } be a time series (e.g. the number of dengue cases at time t monthly, weekly or otherwise). The interest lies in predicting whether the process will upcross a fixed level u at time t + h: Y t+l 1 < u Y t+l A naive way to proceed is to foretell at time t that Y t+l will upcross u if a point predictor, Ŷt+l,t, say upcrosses some level û. Ŷ t+l,t = E [Y t+l Y s, < s t, l > 0], Since V (Ŷt+l,t) < V (Y t+l,t ) it is reasonable to take û < u. However this alarm system (Lindgren, 1985), does not have a good performance on the ability to: detect the events, locate them accurately in time and give as few false alarms as possible. 4 of 28

Warning systems - basic ideas Let {Y t }, t = 1, 2,..., be a discrete parameter stochastic process. Consider at time t and for some q > 0, D t = {y 1,...,y t q } be the informative experiment (data) Y 2,t = {Y t q+1,...,y t } be the present experiment Y 3,t = {Y t+1,...} be the future experiment The event of interest C t (e.g., the process will upcross a fixed level u) is any event in the σ-field generated by Y 3,t. 5 of 28

Warning systems - basic ideas Let {Y t }, t = 1, 2,..., be a discrete parameter stochastic process. Consider at time t and for some q > 0, D t = {y 1,...,y t q } be the informative experiment (data) Y 2,t = {Y t q+1,...,y t } be the present experiment Y 3,t = {Y t+1,...} be the future experiment The event of interest C t (e.g., the process will upcross a fixed level u) is any event in the σ-field generated by Y 3,t. The objective is to construct a region (event predictor) so that whenever the process enters the region a warning (alarm) is given for the event of interest. An event predictor A t (warning region) for C t is any event in the σ-field generated by Y 2,t. 5 of 28

Warning systems - basic ideas The construction of that region is based on an optimality criterion; a warning (alarm) system is said to be optimal when for a set of available data it possesses the highest probability of correctly detecting the event giving as few false alarms as possible. The predictive probabilities P(C t A t, D t ) = γ t and P(A t D t ) = α t are the probability of correct detection and size of the warning region, respectively. 6 of 28

Warning systems - basic ideas The construction of that region is based on an optimality criterion; a warning (alarm) system is said to be optimal when for a set of available data it possesses the highest probability of correctly detecting the event giving as few false alarms as possible. The predictive probabilities P(C t A t, D t ) = γ t and P(A t D t ) = α t are the probability of correct detection and size of the warning region, respectively. A t is optimal of size α t if A t = {y 2 R q : P(C t y 2, D t ) P(C t D t ) k t }, where k t is such that P(A t D t ) = α t. 6 of 28

Operating characteristics of the warning system The following predictive probabilities are the operating characteristics of the warning system. 1. Warning size: P(A t D t ) 2. probability of correct detection: P(C t A t, D t ) 3. probability of correct warning: P(A t C t, D t ) 4. probability of false warning P(A t C c t, D t ) 5. probability of false detection P(C t A c t, D t ) It is an on-line warning system since the informative experiment constantly updates posterior probabilities of the events. 7 of 28

Objective The aim of this work is to develop a warning system for disease outbreak by: the construction of a critical region (event predictor A t ) so that whenever a vector of variables related to the disease occurrence ({X t } e.g. weather conditions) enters the critical region, a warning (alarm) is given for the event of interest C t (e.g. the process {Y t } will upcross a fixed level u) 8 of 28

Alternative warning system The warning system described does not answer the question of interest: relating the process {Y t } (dengue cases) with the processes {X t } = ({X 1,t }, {X 2,t }) (weather conditions: precipitation and temperature). A simple alternative is to construct a joint model using [Y t {X t }][{X t }]. But how? 9 of 28

Alternative warning system The warning system described does not answer the question of interest: relating the process {Y t } (dengue cases) with the processes {X t } = ({X 1,t }, {X 2,t }) (weather conditions: precipitation and temperature). A simple alternative is to construct a joint model using [Y t {X t }][{X t }]. But how? By using a screening procedure as in epidemiological studies. Most papers dealing with this issue (e.g. Lowe, et al 2010, Vasquez-Prokopec et al 2010) consider a Poisson regression model for [Y t {X t } = {x t }], but no attempt is made to model {X t }. 9 of 28

10 of 28 Proposed methodology

Warning system based on screening Let l be the lag with which the warning for time t + l, based on the observations of the process {X t }, is supposed to be given. 11 of 28

Warning system based on screening Let l be the lag with which the warning for time t + l, based on the observations of the process {X t }, is supposed to be given. Again Y 3,t = {Y t+l,...} is the future experiment; the event of interest C t is that Y t+l > u, for some level u; 11 of 28

Warning system based on screening Let l be the lag with which the warning for time t + l, based on the observations of the process {X t }, is supposed to be given. Again Y 3,t = {Y t+l,...} is the future experiment; the event of interest C t is that Y t+l > u, for some level u; Now, the present experiment is X 2,t = {X t q+1...,x t }; 11 of 28

Warning system based on screening Let l be the lag with which the warning for time t + l, based on the observations of the process {X t }, is supposed to be given. Again Y 3,t = {Y t+l,...} is the future experiment; the event of interest C t is that Y t+l > u, for some level u; Now, the present experiment is X 2,t = {X t q+1...,x t }; Similarly, the event predictor A t (warning region) for C t is any event in the in the σ-field generated by X 2,t. 11 of 28

Warning system based on screening Let l be the lag with which the warning for time t + l, based on the observations of the process {X t }, is supposed to be given. Again Y 3,t = {Y t+l,...} is the future experiment; the event of interest C t is that Y t+l > u, for some level u; Now, the present experiment is X 2,t = {X t q+1...,x t }; Similarly, the event predictor A t (warning region) for C t is any event in the in the σ-field generated by X 2,t. The informative experiment (data) is D t = {(Y 1,X 1 ),...(Y t q,x t q )}, ie, all the data available till time t q. This is used to obtain the posterior distribution for the parameters of the model. 11 of 28

Warning system based on screening Now A t is optimal of size α t if A t = {x 2 R pq : P(C t x 2, D t ) P(C t D t ) k t }, where p is the dimension of the vector X and k t is such that P(A t D t ) = α t. 12 of 28

Warning system based on screening Now A t is optimal of size α t if A t = {x 2 R pq : P(C t x 2, D t ) P(C t D t ) k t }, where p is the dimension of the vector X and k t is such that P(A t D t ) = α t. Note that, since P(C t D t ) does not depend on x 2, it can be disregarded and hence A t = {x 2 R pq : P(C t x 2, D t ) k t }, where k t is such that P(A t D t ) = α t. 12 of 28

Warning system based on screening Now A t is optimal of size α t if A t = {x 2 R pq : P(C t x 2, D t ) P(C t D t ) k t }, where p is the dimension of the vector X and k t is such that P(A t D t ) = α t. Note that, since P(C t D t ) does not depend on x 2, it can be disregarded and hence A t = {x 2 R pq : P(C t x 2, D t ) k t }, where k t is such that P(A t D t ) = α t. If p > 1, in practice values of q > 1 can complicate the analysis unnecessarily. 12 of 28

Model Adopting a Bayesian framework, the joint model for [Y t+l,x t ] is described as follows: 1. [Y t+l X t = x t,z,θ][x t ψ], where z contains any extra information; 2. [θ,ψ] = [θ][ψ]. Construction of the region and calculation of operating characteristics (OC) can be obtained via Monte Carlo Methods if no analytical solution is available. We used p = 2, q = 1 and hence, at time t, the present experiment is just X 2,t = {X 1,t, X 2,t }, (precipitation and temperature) 13 of 28

Implementation of the procedure 1 Simulate θ (i), i = 1,..., M from the posterior distribution of θ based on the informative experiment D t 14 of 28

Implementation of the procedure 1 Simulate θ (i), i = 1,..., M from the posterior distribution of θ based on the informative experiment D t 2 Simulate N values x (j) 2 from the predictive distribution X 2 D t 14 of 28

Implementation of the procedure 1 Simulate θ (i), i = 1,..., M from the posterior distribution of θ based on the informative experiment D t 2 Simulate N values x (j) 2 from the predictive distribution X 2 D t 3 Define a grid of values x 2 from the present experiment. Call it G. This grid of values will be necessary to compute the warning region A t. 14 of 28

Implementation of the procedure 1 Simulate θ (i), i = 1,..., M from the posterior distribution of θ based on the informative experiment D t 2 Simulate N values x (j) 2 from the predictive distribution X 2 D t 3 Define a grid of values x 2 from the present experiment. Call it G. This grid of values will be necessary to compute the warning region A t. 4 Let u be the threshold. For each x 2 G compute the predictive probability P(Y t+l > u X t = x 2, z, D t ) 1 M P(Yt+l > u X t = x 2, z, θ (i) ) 14 of 28

Implementation of the procedure 1 Simulate θ (i), i = 1,..., M from the posterior distribution of θ based on the informative experiment D t 2 Simulate N values x (j) 2 from the predictive distribution X 2 D t 3 Define a grid of values x 2 from the present experiment. Call it G. This grid of values will be necessary to compute the warning region A t. 4 Let u be the threshold. For each x 2 G compute the predictive probability P(Y t+l > u X t = x 2, z, D t ) 1 M P(Yt+l > u X t = x 2, z, θ (i) ) 5 For a fixed k register the values of x 2 for which the predictive probability is above k. These values belong to the region A t 14 of 28

Implementation of the procedure 1 Simulate θ (i), i = 1,..., M from the posterior distribution of θ based on the informative experiment D t 2 Simulate N values x (j) 2 from the predictive distribution X 2 D t 3 Define a grid of values x 2 from the present experiment. Call it G. This grid of values will be necessary to compute the warning region A t. 4 Let u be the threshold. For each x 2 G compute the predictive probability P(Y t+l > u X t = x 2, z, D t ) 1 M P(Yt+l > u X t = x 2, z, θ (i) ) 5 For a fixed k register the values of x 2 for which the predictive probability is above k. These values belong to the region A t 6 Find the boundaries of the region A t so that it is well defined. 14 of 28

Implementation of the procedure 7 Compute the size of this region, ie, the predictive probability P(A t D t ) 1 N IAt (x (j) 2 ). 15 of 28

Implementation of the procedure 7 Compute the size of this region, ie, the predictive probability P(A t D t ) 1 N IAt (x (j) 2 ). 8 Compute P(Y t+l > u,x 2 A t ) 1 N P(Yt+l > u x (j) 2, z, D t)i At (x (j) 2 ) 15 of 28

Implementation of the procedure 7 Compute the size of this region, ie, the predictive probability P(A t D t ) 1 N IAt (x (j) 2 ). 8 Compute P(Y t+l > u,x 2 A t ) 1 N P(Yt+l > u x (j) 2, z, D t)i At (x (j) 2 ) 9 Similarly compute P(Y t+l > u,x 2 / A t ). 15 of 28

Implementation of the procedure 7 Compute the size of this region, ie, the predictive probability P(A t D t ) 1 N IAt (x (j) 2 ). 8 Compute P(Y t+l > u,x 2 A t ) 1 N P(Yt+l > u x (j) 2, z, D t)i At (x (j) 2 ) 9 Similarly compute P(Y t+l > u,x 2 / A t ). 10 P(Y t+l > u D t ) = P(Y t+l > u,x 2 A t ) + P(Y t+l > u,x 2 / A t ). 15 of 28

Implementation of the procedure 7 Compute the size of this region, ie, the predictive probability P(A t D t ) 1 N IAt (x (j) 2 ). 8 Compute P(Y t+l > u,x 2 A t ) 1 N P(Yt+l > u x (j) 2, z, D t)i At (x (j) 2 ) 9 Similarly compute P(Y t+l > u,x 2 / A t ). 10 P(Y t+l > u D t ) = P(Y t+l > u,x 2 A t ) + P(Y t+l > u,x 2 / A t ). 11 All the operating characteristics (OC) can then be computed from [7:10]. 15 of 28

Implementation of the procedure 7 Compute the size of this region, ie, the predictive probability P(A t D t ) 1 N IAt (x (j) 2 ). 8 Compute P(Y t+l > u,x 2 A t ) 1 N P(Yt+l > u x (j) 2, z, D t)i At (x (j) 2 ) 9 Similarly compute P(Y t+l > u,x 2 / A t ). 10 P(Y t+l > u D t ) = P(Y t+l > u,x 2 A t ) + P(Y t+l > u,x 2 / A t ). 11 All the operating characteristics (OC) can then be computed from [7:10]. 12 Choose the k which gives better OC. 15 of 28

Implementation of the procedure 7 Compute the size of this region, ie, the predictive probability P(A t D t ) 1 N IAt (x (j) 2 ). 8 Compute P(Y t+l > u,x 2 A t ) 1 N P(Yt+l > u x (j) 2, z, D t)i At (x (j) 2 ) 9 Similarly compute P(Y t+l > u,x 2 / A t ). 10 P(Y t+l > u D t ) = P(Y t+l > u,x 2 A t ) + P(Y t+l > u,x 2 / A t ). 11 All the operating characteristics (OC) can then be computed from [7:10]. 12 Choose the k which gives better OC. 15 of 28

16 of 28 Application

Description of the data RJ data: monthly notified cases of dengue (Y t ) for the 33 health administrative regions in the city of Rio de Janeiro (RJ), Brazil. RJ total population: 5,857,904 The warning region is built based on X 1,t preciptation (known for all 33 regions) and X 2,t temperature (common to all regions). RJ data: region 12 dengue cases 0 16 34 71 97 121 164 223 300 1 4 13 16 25 28 37 40 49 52 61 64 73 76 month 17 of 28

Preliminary analysis A preliminary data analysis (cross correlations) suggested a lag l = 2 months Box-Cox transformation applied to maximum temperature (λ = 2.65) and total amount of precipitation (λ = 0.54) [Y t+l X t = x t, z, θ] Spatio-temporal Poisson regression model with transformed temperature and precipitation as covariates. [X t ψ] Bivariate Gaussian model for the joint distribution of temperature and precipitation. Also a nonparametric Bayesian model was tested. 18 of 28

Spatio-temporal Poisson regression model for the incidence of dengue (7 years of monthly data) Dengue incidence per 100,000hab. in RJ 2007 observed under 50 50 150 150 300 over 300 Dengue incidence per 100,000hab. in RJ 2007 CAR model under 50 50 150 150 300 over 300 19 of 28

Region 12 - warning region for u = 40, k = 0.3 RJ region 12 f(temperature) 2 4 6 8 Y> 40 Y<= 40 temperature 20 25 30 35 40 45 Y> 40 Y<= 40 0 10 20 30 40 0 100 200 300 f(precipitation) precipitation Epidemic: 300 cases/100,000 inhab/year. Region 12: 161,178*(300/12)/100,000 40 cases/month. 20 of 28

Region 12 - warning region, new cases RJ region 12 f(temperature) 2 4 6 8 Y> 40 Y<= 40 temperature 20 25 30 35 40 45 Y> 40 Y<= 40 new cases 0 10 20 30 40 0 100 200 300 f(precipitation) precipitation 21 of 28

Region 12 - Operating characteristics Operating Characteristics (fixed - based on all available data), u = 40, k = 0.3, (yearly incidence rate - 298 in 100,000) Probability of the event: P(Y > 40 D) = 0.20 (empirical estimate 0.16) Warning region size P(A t D t ) = 0.25 Probability of correct detection P(C t A t, D t ) = 0.64 Probability of correct warning P(A t C t, D t ) = 0.80 Probability of false warning P(A t Ct c, D t ) = 0.11 Probability of false detection P(C t A c t, D t ) = 0.05 22 of 28

23 of 28 Discussion

Discussion and further work This is a work under progress; spatial data on temperature for Rio de Janeiro has just become available. The topography of RJ makes particularly difficult the spacial analysis of dengue. This warning system, as it was devised, is not time dependent. Warning region is fixed. However it is possible to improve on the model in order to construct a recursive system of warning regions. This is our next goal. Include in the model socio-economic and other environment characteristics which are relevant to explain dengue epidemics. Consider the construction of spatio-temporal warning systems. 24 of 28

25 of 28 References

References Amaral-Turkman, M.A., Turkman, K.F., 1990. Optimal alarm systems for autoregressive process; a Bayesian approach. Computational Statistics and Data Analysis 19, 307-314. Antunes, M., Amaral-Turkman, M.A., Turkman, F.K., 2003. A Bayesian approach to event prediction. Journal of Time Series Analysis 24, 631-646. Baxevani, A, Wilson, and Scotto, M. (2011). Prediction of Catastrophes in Space over Time. Preprint 2011/9. University of Gothenburgh, Chalmers University of Technology Cirillo, P. and Husler, J. (2011) Alarm systems and catastrophes from a diverse point of view. Technical Report, University of Bern. Costa, C., Scotto, M.G., and Pereira, I. (2010) Optimal alarm systems for FIAParch processes REVSTAT, 8, pp. 37-55. de Maré, J., 1980. Optimal prediction of catastrophes with application to Gaussian process. Annals of Probability 8, 841-850. Grage, H., Holst, J., Lindgren, G., Saklak, M., 2010. Level crossing prediction with neural networks. Methodology and Computing in Applied Probability 12, 623-645. Lindgren, G., 1975b. Prediction of catastrophes and high level crossings. Bulletin of the International Statistical Institute 46, 225-240. Lindgren, G., 1980. Model process in non-linear prediction, with application to detection and alarm. Annals of Probability 8, 775-792. Lindgren, G., (1985). Optimal Prediction of Level Crossings in Gaussian Processes and Sequences Ann. Probab., 13, Number 3, pp. 804-824. 26 of 28

References Lowe R, Bailey TC, Stephenson DB, Graham RJ, Coelho CAS, Sá Carvalho M, Barcellos C. (2010). Spatio-temporal modelling of climate-sensitive disease risk: Towards an early warning system for dengue in Brazil. Computers & Geosciences (in Press). Monteiro, M., Pereira, I., Scotto, M.G., 2008. Optimal alarm systems for count process. Communications in Statistics: Theory and Methods 37, 3054-3076. Svensson, A., Lindquist, R., Lindgren, G., 1996. Optimal prediction of catastrophes in autoregressive moving average processes. Journal of Time Series Analysis 17, 511-531. Svensson, A. and Hoslt,J. (1997). Prediction of high water levels in the Baltic. Journal of the Turkish Statistical Association, 1, 39-46. Svensson, A. and Hoslt,J. (1998). Optimal prediction of events in Time Series. Technical Report 1998:9. Lund University. Turkman, K. F. and Amaral Turkman, M.A., (1989). Optimal Screening Methods. J. R. Statist. Soc. B, 51, No.2, pp. 287-295. Vasquez-Prokopec GM, Kiltron,U., Montgomery B., Horne P. and Ritchie SA (2010). Quantifying the Spatial Dimension of Dengue Virus Epidemic Spread within a Tropical Urban Environment. PLOS Neglected Tropical Diseases, 4, issue 12, e920 27 of 28

This research has been partially supported by National Funds through FCT Fundação para Ciência e Tecnologia, projects PTDC/MAT/118335/2010 and PEst-OE/MAT/UI0006/2011 Thank you very much for your attention! 28 of 28