APLICACION DEL MODELAMIENTO MATEMATICO EN LA
Transcription
APLICACION DEL MODELAMIENTO MATEMATICO EN LA
Dr aft APLICACION DEL MODELAMIENTO MATEMATICO EN LA PREDICCION DE ESCENARIOS DE RIESGO EN EPIDEMIOLOGIA Carlos Castillo-Chavez1 Regents Professor, Director Joaquin Bustoz Professor of Mathematical Biology Simon A. Levin Mathematical, Computational and Modeling Sciences Center Tempe, AZ 85287-1904, USA Universidad de Lima Lima, Peru Miercoles, November 25, 2015 1 [email protected];: https://twitter.com/mcmsc01 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Steven Strogatz. The Real Scientific Hero of 1953. New York Times (1923-Current file), page 1, 2003. Three ways of doing science brought by James D. Watson and Francis Crick & the inventors of the computer experiment: Enrico Fermi, John Pasta and Stanislaw Ulam. The computer experiment offered a third way of doing science. Data Science (Big Data) is the fourth way of doing science APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 2 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Enrico Fermi, John Pasta and Stanislaw Ulam – in 1953 invented the concept of a "computer experiment. "... the most important lesson ...is how feeble even the best minds are at grasping the dynamics of large, nonlinear systems. Faced with a thicket of interlocking feedback loops, where everything affects everything else, our familiar ways of thinking fall apart. To solve the most important problems of our time, we’re going to have to change the way we do science." NYT 2003, S. Strogatz APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 3 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Training of Mathematical Scientists for the 21st Century “... As Fermi and his colleagues taught us, a complex system like cancer can’t be understood merely by cataloging its parts and the rules governing their interactions. The nonlinear logic of cancer will be fathomed only through the collaborative efforts of molecular biologists.” (Strogatz, 2003). The world’s ability to train 21st century mathematical scientists must rely on models of learning and thinking embedded within interdisciplinary educational research/mentorship models. Mathematical scientists must become proficient on multiple models of doing science including the systematic use of computer experiments and in data science. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 4 / 64 Dr aft Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Source: hlp://www.datasciencecentral.com/forum/topics/the-‐3vs-‐that-‐define-‐big-‐data APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 5 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft OakRidgeNaTonalLaboratory-June6,2013 Cray-madeTitan–thefastestcomputerintheworld Chinaannouncesfastercomputer Milky–Way2onJune17,2013 hl p://www.voanews.com/content/china-boasts-worldsfastest-computer/1683465.html APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 6 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d A Brief History Block of Mathematical Epidemiology Daniel Bernoulli (1700–1782) Dr aft The field was the result of the work of medical doctors - mathematical scientists Sir Ronald Ross (1857–1932) Anderson G. McKendrick (1876–1943) William O. Kermack (1898–1970) www.fameimages.com/daniel-bernoulli www.nobelprize.org/nobel_prizes/medicine/laureates/1902/ross-bio.html www.york.ac.uk/depts/maths/histstat/people/ Photograph courtesy of Godfrey Argent Studios APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 7 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d The mathematical theory of infectious diseases started by medical doctors Dr aft Sir Ronald Ross (1857–1932) www.nobelprize.org/nobel_prizes/medicine/laureates/1902/ross-bio.html Nobel Laureate 1902 APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 8 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Basic Malaria Model The Life–cycle of malaria parasites Ross-Macdonald Model Dr aft x : Proportion of infected humans y : Proportion of infected mosquitoes Parameter M N a b r µ dx dt = ab M N y (1 − x) − rx dy dt = ax (1 − y) − µy Definition Number of female mosquitoes per human host Biting rate on a human per mosquito Infected mosquito to human transmission efficiency Per capita human recovery rate Per capita mortality rate of mosquitos APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center Units day−1 day−1 day−1 9 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Basic Reproductive Number for Malaria R20 = ma2 b µr Biological interpretation R20 is the number of secondary cases of infection on hosts or vectors generated by a single infective host or infective vector. a – number of bites per unit time b – infected bites that produce an infection m= 1 r 1 µ M N – number of female mosquitoes per human host – duration of infection in human – lifetime of a mosquito APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 10 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Holistic Perspective on Malaria Dr aft How can we use what we learned from person to vector to person or vector to host to vector transmission at higher levels of organization? Holistic view - Public good: Can malaria be controlled at higher levels of organization? Problem across scales: how do we use knowledge at the individual level to understand phenomena at the population level? Validation of proposed control policies via the existence of a threshold: the prestige of mathematics and mathematical modeling Power of abstraction, can we use this framework elsewhere: STDs APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 11 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Gonorrhea: Transmission Dynamics and Control University of Iowa Kenneth Cooke James A. Yorke Dr aft Herbert Hethcote Pomona College University of Maryland, College Park Herbert Hethcote and Jim Yorke changed health policy with their work on gonorrhea via their concept of Core Group Ken Cooke and Jim Yorke expanded significantly the work of Ross in 1970s with their work on Gonorrhea transmission and control APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 12 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Ross’ "students" Kermack and McKendrick Anderson Gray McKendrick (1876–1943) Photograph courtesy of Godfrey Argent Studios www.york.ac.uk/depts/maths/histstat/people/ Dr aft William Ogilvy Kermack (1898–1970) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 13 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Index case Dr aft The basic reproduction number for the SIR model without vital dynamics Infected T(4) T(3) T(2) T(1) Susceptible T(0) Infected Susceptible Index case R0=2 No Transmission Transmission The basic reproduction number, R0 , defined as the number of secondary cases generated by a typical infectious individual during its period of infectiousness in an entirely susceptible population. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 14 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft System of equations without vital dynamics - single outbreak S dS dt dI dt dR dt SI , N SI = β − γI, N = −β = γI, N = S + I + R. APLICACION DEL MODELAMIENTO β IS I States S I R Parameters β γ Carlos Castillo-Chavez γ R Meaning # of Susceptible # of Infectecd # of Recovered Meaning Transmission coefficient Per-capita recovery rate Simon A. Levin Modeling Center 15 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft On the basic reproduction number R0 R0 = β γ 1 R0 depends on number of contacts and probability of transmission (both quantities captured by β) and the infectious period (1/γ). 2 If R0 < 1 then the infection dies out. 3 If R0 > 1 then an epidemic ensues 4 Accurate estimation of the value of the reproductive number are central in the planning of control of intervention efforts. → The goal of public health interventions can often be reduced to that of bringing R0 below 1. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 16 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Model fitting and predictions using Influenza outbreak data Dr aft Estimate parameters from data using the SIR model Prevalence of an influenza outbreak in a boys boarding school, in the UK, 1978. 300 Total population size: N = 763, 150 1978 UK Boarding School Data Best fit Parameter estimates and standard 250 200 error: β̂ = 1.6682 ± 0.0294 days−1 γ̂ = 0.4417 ± 0.0177 days1 100 Initial # of susceptible: S0 = 762, 50 Initial # of infectives: I0 = 1. 0 0 2 4 6 8 10 12 14 SIR epidemic model simulated with estimated parameters Infective Fraction(I) 0.2 0 0 S+ 5 Population Size 0.2 0 0 0.2 0.4 0.6 0.8 Susceptible Fraction (S) Carlos Castillo-Chavez 10 15 20 25 Time (Days) 1 I 0.4 Infective 0.1 = APLICACION DEL MODELAMIENTO 0.6 0.3 N Initial conditions: S(0) = 762, I(0) = 1, R(0) = 0. 0.8 Infective Fraction (I) Parameter values: β = 1.6682, γ = 0.4417 0.4 S − I Phase Plane Por tr ait 1 1 0.5 0 0 5 10 15 Time (Days) Simon A. Levin Modeling Center Susceptible Recovered S (25) = 0. 02 20 25 17 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Sara del Valle Dr aft Computational Epidemiology: The case of EpiSims MTBI alumni – now a leading scientist Research Interests: Develop mathematical and computational models to help mitigate he spread of infectious diseases. (EpiSims slides courtesy of Sara del Valle et al.) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 18 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Typical Family Day- Families using Same Locations P. Stroud, S. Del Valle, S. Sydoriak, J. Riese, S. Mniszewski, Spatial dynamics of pandemic influenza in a massive artificial society, Journal of Artificial Societies and Social Simulation, 10, (4) (2007) 9. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 19 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Mobility in a Network Simulation Dr aft G. Chowell, J. M. Hyman, S. Eubank, and C. Castillo-Chavez. Scaling laws for the movement of people between locations in a large city. Phys. Rev. E, 68, 066102 – Published 15 December 2003 APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 20 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Portland-Simulated Flu Pandemic-75% stay at home S. Eubank, H. Guclu, V. S. Anil Kumar, M. V. Marathe, A. Srinivasan, Z. Toroczkai, N. Wang, Modelling disease outbreaks in realistic urban social networks, Nature 429 (6988) (2004) 180–184. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 21 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Heterogeneous Spread APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 22 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Characteristics of the 2014 Ebola epidemic Dr aft G Chowell, N W Hengartner, C Castillo-Chavez, P W Fenimore, and J M Hyman. The basic reproductive number of Ebola and the effects of public health measures: the cases of Congo and Uganda J Theor Biol, 229(1):119–126, Jul 2004. The causative Ebola strain in west Africa is closely related to a strain associated with past outbreaks in Central Africa Likely common reservoir: Fruit bats Epidemiological characteristics include: R0 ∼ 2.0 (substantial uncertainty) Incubation period 11 days Serial interval 15 days Case fatality ratio 70.8% (95% IC 68.6 − 72.8%) Photograph courtesy of AP Photo/Abbas Dulleh High mortality rate (50-90% in previous outbreaks, 70% currently) Bodily fluids are highly infectious, as are the unburied dead APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 23 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft 2014 West African Outbreak Index case Dec 2013, 2 year old girl in mountainous region of Guinea Porous borders and trafficking have likely aided the spread of the disease (distribution as of Oct 6th., 2014 Image source: bbc.com) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 24 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft What is unique about this epidemic? Affected region lacked experience with EVD outbreaks Substantial delays in detection and implementation of control interventions in a region characterized by porous borders and high population movement Limited public health infrastructure in affected region including epidemiological surveillance systems and diagnostic testing Unsafe burials and health-care settings contributed to seeding the epidemic in multiple districts and across borders APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 25 / 64 Dr aft Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d http://www.bbc.com/news/world-africa-28755033 APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 26 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Example 1: Exponential rise in new cases APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Dr. Sherry Towers (Faculty, ASU) Dr. Oscar Patterson (Postdoc, Harvard Univ) Simon A. Levin Modeling Center 27 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Example 1: Exponential rise in new cases APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 28 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Exponential rise in new cases www.newfluwiki2.com Early in an epidemic, when the population is predominantly naive, initial rise in cases is exponential, When everybody is susceptible the reproduction number is called R0 , The Effective Reproduction Number measures the changes in exponential growth as a function of time (Reff (t)), Reff (t) is the average number of new cases one case will cause over the course of their infection at time t. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 29 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Reproduction number In closed populations, Reff (t) usually declines as an epidemic progresses (fewer and fewer naïve people available to infect) As an epidemic progresses social distancing due to fear can also cause additional reductions in Reff (t) But poorly designed control strategies can, unfortunately, potentially do more harm than good. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 30 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Temporal variations in Reff (t) Temporal variations in the effective reproduction number of the 2014 West Africa Ebola outbreak Rate of exponential rise, in conjunction with a mathematical model of the spread of the disease, can be used to determine Reff (t). For instance, SEIRD model for Ebola. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 31 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Temporal variations in Reff (t) contd... Dr aft Developed a simple, model-independent way to determine if the relative transmission rate of a disease in a closed population appears to increase or decrease in time; Method applies piece-wise exponential fits to the time series of cases in outbreak to determine if the rate of exponential rise in cases increases over time (evidence that effective Reff (t) is increasing). APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 32 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Example 2: Research question Volume 15, Issue 2, February 2015, Pages 148–149 Modelling the effect of early detection of Ebola Diego Chowella, b, Carlos Castillo-Chaveza, Sri Krishnab, Xiangguo Qiuc, Karen S Andersonb, a Simon A Levin Mathematical, Computational and Modeling Sciences Center, Biodesign Institute, Arizona State University, Tempe, AZ, USA b Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA c National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, MB, Canada Copyright © 2015 Elsevier Ltd. All rights reserved What is the effect of pre-symptomatic stage Ebola Virus detection on its transmission dynamics? Diego Chowell (PhD student) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 33 / 64 Dr aft Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez • Twenty'four,“asymptoma2c”,individuals, exposed,to,Ebola,were,tested,using,P.C.R.,, • Eleven,of,the,exposed,pa2ents,eventually, developed,the,infec2on.,, • Seven,of,the,11,tested,posi2ve,for,the, P.C.R.,assay;,none,of,the,other,13,did., Simon A. Levin Modeling Center 34 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Modeling the effect of early detection of Ebola The polymerase chain reaction (PCR) can detect Ebola virus in both human beings and non-human primates in the pre-symptomatic stage. We evaluated the potential effect of early diagnosis of pre-symptomatic individuals in west Africa. We used a simple mathematical model calibrated to the transmission dynamics of Ebola virus in west Africa. The baseline model includes the effects of contact tracing and effective isolation of infectious individuals in health-care settings. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Members of the European Mobile Laboratory Project use PCR tests in Guéckédou, Guinea. G. Vogel, Testing new Ebola tests, Science (2014). Simon A. Levin Modeling Center 35 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d S Class S E1 E2 I J P Dr aft Model of transmission dynamics of Ebola infection incorporating diagnosis of infected and pre-symptomatic individuals E1 E2 Description Susceptible Latent undetectable Latent detectable Infectious and symptomatic Isolated Recovered and Dead APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez I J Parameter 1/k2 1/k2 1/α 1/γ 1/γr P Value 4 days 3 days 3 days 6 days 7 days Simon A. Levin Modeling Center 36 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Predictions on the effect of diagnosing pre-symptomatic individuals on the Ebola epidemic attack rate 100 Effectiveness of isolation 50% Effectiveness of isolation 60% Effectiveness of isolation 65% 90 Attack rate (%) 80 70 60 50 40 30 20 10 0 0 5 10 15 20 25 30 35 40 45 Proportion of latent individuals diagnosed before onset of symptoms (%) 50 We can make now two observations: The effect of early Ebola detection is a function of existing public health measures and resources. There is a tipping point, where early diagnosis of high risk individuals, combined with adequate isolation, can lead to rapid reduction in Ebola transmission. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 37 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Example 3: A disease model framework under virtual dispersal and varying residence times Dr aft Difficulties in defining a contact in the context of communicable diseases. Notion of contact is well-defined in STDs and vector-born diseases. Estimate the average risk of acquiring TB or flu to individuals spending 3 hours on the average per day, in public transportation. http://pilgrimagetoindia.com/gallery/26.html Contacts or variable environmental risks? From differential susceptibility to local environmental risk infectivity. http://www.livetradingnews.com Overall Question: How does environmental pathogen risk defined by risk/transmission vector B and patch residence time distribution P = (pij ) impact disease transmission dynamics and control. Formulation of epidemic models (host parasite dynamics) where risk of infection (parasitism) is a function of local residence times. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 38 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Two approaches to incorporate heterogeneity Eulerian Approach: Patch 1 Focus on the whole population stratified into different patches. Individuals take the identity of the host patch after leaving their residence patch. More realistic for long term dispersal. Lagrangian Approach: 12 p 21 Patch 1 Keep track of individuals for population in each patch through time and space. Focus on the patch level of population interacting between different patches . More realistic for short scale movements. APLICACION DEL MODELAMIENTO Patch 2 p Carlos Castillo-Chavez Patch 2 p12 p21 Simon A. Levin Modeling Center 39 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Model formulation p12 is the proportion of times residents of Patch 1 spend in Patch 2. p21 is the proportion of times residents of Patch 2 spend in Patch 1. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 40 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Patch-specific dynamics We define a Patch-specific basic reproduction number: Ri0 (P) = Ri0 × n X βj j=1 βi pij dbi i . pij Pn bk k=1 pkj d k If Ri0 (P) > 1 then the disease persists in Patch i. If pkj = 0 for all k = 1, .., n, and k 6= i, whenever pij > 0 and Ri0 (P) < 1, then the disease dies out in Patch i. Remarks: • This results also include the non-strongly connected patches case. • The connectivity of Patch i to other patches may promote or suppress endemicity: β Via the presence of high risk patches. For instance, if there exists a patch j such that βj is large i enough. In this last case Patch j is actually a source and Patch i a sink. Whenever individuals spend more time in high risk patches than in low risk patches. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 41 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Findings Dr aft We have used residence times in heterogeneous environments as a proxy for “effective” contacts over a certain window in time; We have formulated general multi-patch SIS epidemic models with residence times that provide conditions for extinction or persistence of the disease at global level and patch-specific level. Derdei Bichara, Yun Kang, Carlos Castillo-Chavez, Richard Horan, and Charles Perrings. SIS and SIR Epidemic Models Under Virtual Dispersal. pages 1–31, 2015. Joint work with: Derdei Bichara APLICACION DEL MODELAMIENTO Yun Kang Carlos Castillo-Chavez Charles Perrings Richard Horan Simon A. Levin Modeling Center 42 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Heterogeneity challenges Dr aft A cordon sanitaire is a medieval control strategy that involves creating boundaries around an area experiencing an epidemic of disease. This strategy was used in 1821 in the border of France and Spain to avert the spread of a deadly fever. Prior 2014, it was last used in 1918 at the Polish-Russian border in an attempt to stop the spread of typhus. cordons sanitaire were used in 2014 in some of the Ebola-stricken countries. The effectiveness of cordons sanitaire is controversial and debatable. Soldiers enforcing the cordon securitaire in Kanema, Sierra Leone (via the NYT) Research question: How does the movement of individuals between a low and high risk area promote, mitigate or suppress disease dynamics? A Lagrangian conceptual framework that models the movement of individuals across different areas keeping track of residence times is used on the Ebola outbreak. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 43 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d 4.5 ×10 4 Infected class patch 1 3 10000 Dr aft 3.5 Infected class patch 2 12000 p12=0 p12=0.15 p12=0.3 p12=0.45 4 p12=0 p12=0.15 p12=0.3 p12=.0.45 8000 2.5 6000 2 1.5 4000 1 2000 0.5 0 0 0 500 1000 1500 Time Figure: 0 500 1000 1500 Time Dynamics of incidence in each patch for p21 = 0 and varying p12 . Parameter values: εD = 1, β1 = 0.35, β2 = 0.1, fdeath = 0.8, k = 1/24, α = 0, ν = 1/2 and γ = 1/5.6. The blue graph is the case where the patches are isolated. The disease reaches its highest pick in the high risk Patch 1 whereas it dies off without a major outbreak in the low risk patch 2. Besides the isolated case, we note that the disease prevalence decreases in both patches as p12 increases. While the results in Patch 1 are expected, the results are counterintuitive in Patch 2, as we expect more infections as the flow of individuals from the high risk area increases. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 44 / 64 Dr aft Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Figure: Dynamics of the cumulative incidence in each patch for p21 = 0 and varying p12 . The predicted dynamics of the overall infected individuals is similar to those in Patch 1 since it is assumed that the high risk Patch 1 is overpopulated when compared to the low risk Patch 2. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 45 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Conclusion A conceptual framework to test the effectiveness of control strategies aimed at limiting the movements of individuals across different risk areas has been introduced. It was observed, for example, that increases in the time that residents of high risk areas spend in low risk areas do not necessarily generates notable prevalence increases in low risk areas. Joint work with: Baltazar Derdei APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Victor Simon A. Levin Modeling Center 46 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Mass Media and contagion of fear Dr aft Sherry Towers, Shehzad Afzal, Gilbert Bernal, Nadya Bliss, Shala Brown, Baltazar Espinoza, , et al. Mass media and the contagion of fear: The case of ebola in america. PLoS ONE, 10(6):e0129179 EP –, 06 2015. Ebola related searches and tweets originating in the U. S. during the outbreak tied in to public interest or panic. Of interest, how would public interest, curiosity, or panic on certain topic affects social media and Internet search dynamics? A mathematical model has been employed to simulate the potential influence of Ebola-related news videos on peoples’ tendency to perform Ebola-related Internet searches or tweets. Fits of the news media contagion model, and a simple linear regres model, to the sources of data used in this study. Overall Goal: Determine if news coverage was a significant factor on the temporal patterns in Ebola-related Internet and Twitter data. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 47 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft News on Ebola Significant evidence of contagion was found, with each Ebola-related news video inspiring tens of thousands of Ebola-related tweets and Internet searches. There is no significant evidence of contagion due to effects other than news videos. There is no statistically significant evidence that people return to the susceptible class after recovery. In all cases, the contagion model had a better predictive power than the linear regression model. There is no statistically significant evidence that Ebola-related Internet searches and tweets Granger-cause temporal patterns in Ebola-related news videos, but there is evidence in several cases that the reverse is true. APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 48 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d SIR with diffusion Dr aft SIR no diffusion Ṡ = −βSI İ = βSI − αI Standard model with diffusion St = −βSI + Ds Sxx It = βSI − αI + Di Ixx APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 49 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Necessary and sufficient conditions for Aggregation Turin’s Method Superposition and Instability ci (x, t) = αi cos(qx)eσt ∂c1 ∂t ∂c2 ∂t values of q s.t. <(σ) > 0 α1 (σ − a11 + D1 q2 ) − α2 a12 = 0 ∂ 2 c1 ∂2x ∂ 2 c2 = a21 c1 + a22 c2 + D2 2 ∂ x = a11 c1 + a12 c2 + D1 −α1 a21 + α2 (σ − a22 + D2 q2 ) = 0 Necessary and Sufficient Conditions APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez 1 a11 + a22 < 0 2 a11 a22 − a12 a21 > 0 3 a11 pD2 + a22 D1 > 2 D1 D2 (a11 a22 − a12 a21 ) Simon A. Levin Modeling Center 50 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft RESULT K. E. Yong, E. Díaz Herrera, and C. Castillo-Chavez. From bee species aggregation to models of disease avoidance: The Ben − Hur effect. ArXiv e-prints, October 2015. ∂S ∂t ∂I1 ∂t ∂I2 ∂t ∂2S β SI1 + αI2 + DS 2 1 + I2 ∂x 2 β ∂ I1 = SI1 − δI1 + DI1 2 1 + I2 ∂x 2 ∂ I2 = δI1 − αI2 + DI2 2 ∂ x = − (1) Theorem (Diffusive Instability in Epidemics) The linearization of the system (1) satisfies the necessary and sufficient conditions for instability if and only if βδ > 1 and αβ > 1 APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 51 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Different diffusion rates: linear model time = 0 time = 6 0 20 20 40 40 60 60 80 80 0 20 40 60 80 0 time = 19 0 20 20 40 40 60 60 80 80 20 40 60 80 time = 38 20 20 40 40 60 60 80 80 0 20 40 20 40 60 20 40 20 20 20 40 40 40 60 60 60 60 80 80 80 80 0 20 60 80 40 60 80 20 40 20 0 20 40 80 60 80 0 20 20 20 20 40 40 40 40 60 60 60 80 20 40 60 80 20 40 60 80 0 20 time = 38 40 80 0 0 20 20 20 20 40 40 40 40 60 60 60 80 60 80 20 40 60 80 0 20 40 60 80 60 80 60 80 0 40 time = 50 0 40 20 time = 44 0 20 80 80 60 0 0 60 60 80 0 40 time = 31 0 0 20 time = 25 0 D2 D1 APLICACION DEL MODELAMIENTO 80 0 80 80 60 0 time = 50 60 40 time = 19 80 0 0 time = 31 60 time = 13 0 40 time = 44 0 time = 6 0 20 80 0 0 time = 0 0 time = 25 0 0 time = 13 0 Dr aft 0 80 60 80 0 20 40 D2 > D1 Carlos Castillo-Chavez Simon A. Levin Modeling Center 52 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Different diffusion rates: nonlinear model u 1 0.5 0 150 2 0 −2 140 120 140 100 100 150 120 80 100 60 80 100 50 60 40 40 20 50 20 0 0 0 Slow aggregation Fast aggregation APLICACION DEL MODELAMIENTO 0 Carlos Castillo-Chavez Simon A. Levin Modeling Center 53 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Beyond Ebola: lessons to mitigate future pandemics < Volume Previous Article 3, . 7, No – 354 355, e e July 2015 Next Article > Access this article on ScienceD Comment Beyond Ebola - , Carlos Castillo Chavez , Poste : lessons to mitigate future pandemics , Roy Curtiss Peter Daszak , , Simon A Levin - , Oscar Patterson Lomba , Charles Perrings George Sherry Towers Open Access : DOI // : http . . /10.1016/ 2214-109 (15)00068-6 dx doi org S X Article Info Summary Full Text References It is now just more than a year since the official confirmation of an outbreak of Ebola haemorrhagic fever in west Africa .1 With new cases occurring at their lowest rate for , outbreak in sight for all three countries predominantly affected , strategies to prevent future outbreaks of this like many other emerging diseases , , and other 2015,2 and the end of the now is the time to consider . zoonotic pathogens . , The Ebola outbreak , illustrates the crucial role of the ecological , social , political and economic context within which diseases emerge APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 54 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d So what have we learned from influenza pandemics, SARS and Ebola? The cost of management of infectious disease outbreaks is almost always greater than the cost of avoiding them. “For severe acute respiratory syndrome (SARS), the global cost of a single outbreak was estimated to be between US 13 billion and US 50 billion at the currency values of the 2003 outbreak. For Ebola, the cost might be higher? both in the direct, short-term cost of control, patient care, and hospital admission, and in the indirect, longer-term dislocation of the regional economies in west Africa." Lancet Global Health, Volume 3, No. 7, e354-355, 2015) The economic costs of disease emergence are projected to continue to rise in line with increasing frequency of outbreaks driven by expanding socioeconomic and environmental changes that cause diseases. Lancet Global Health, Volume 3, No. 7, e354-355, 2015) Mitigation of future pandemic threats such as Ebola is therefore more cost-effective than the current approach of responding to outbreaks after they have begun to spread rapidly in the human population. Lancet Global Health, Volume 3, No. 7, e354-355, 2015) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 55 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Is it possible to design a strategy for an as-yet unknown pathogen? This task seems daunting, but it has already begun, partly though reduction of the size of the problem and allocation of resources in an objective way to the locations most at risk. (Lancet Global Health, Volume 3, No. 7, e354-355, 2015) “Analysis of trends in disease emergence provides a strategy to identify the places most likely to propagate the next pandemic... hotspots for disease emergence tend to be tropical regions with high wildlife diversity that harbour known or unknown zoonoses, and high levels of socioeconomic and environmental change." Lancet Global Health, Volume 3, No. 7, e354-355, 2015) USAID’s Emerging Pandemic Threats (PREDICT) programme targets these hotspots to identify known and previously unknown viruses in wildlife species known to be zoonotic reservoirs, analyses patterns of high-risk human behaviour, tests people for evidence of these viruses moving across the species barrier, and enables the design of strategies to reduce the risk of even the first spillover event. Lancet Global Health, Volume 3, No. 7, e354-355, 2015) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 56 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Is it possible to generate massive beahviour changes? Targeted programmes for behaviour change, focusing on incentives for bushmeat hunting, should be part of the mitigation strategy...This approach was trialled in central Africa, with education programmes designed to reduce the consumption of primates found dead in forests, and has been shown to off er a cost-eff ective way to mitigate the risk of an Ebola outbreak (Lancet Global Health, Volume 3, No. 7, e354-355, 2015) Projects aimed to reduce dependency on bushmeat need to be supported, either through creative approaches to farming of some wildlife species, or by expansion of livestock production, with appropriate biosecurity and surveillance to prevent emergence of other zoonoses Lancet Global Health, Volume 3, No. 7, e354-355, 2015) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 57 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d What about the use of technology ... training and preparedness? The acceleration of vaccine development for Ebola as part of an outbreak control strategy could also have a crucial role to mitigate future outbreaks. (Lancet Global Health, Volume 3, No. 7, e354-355, 2015) Ebola’s propensity for nosocomial spread (noted in west Africa and in many previous Ebola outbreaks) could be curtailed by preoutbreak vaccination of critical care workers in Ebola virus hotspots. (Lancet Global Health, Volume 3, No. 7, e354-355, 2015) Targeted training in infection control, and efforts to maintain surge capacity between outbreaks, will be crucial for rapid response to the first cases in a future emergence event. (Lancet Global Health, Volume 3, No. 7, e354-355, 2015) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 58 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Can these approaches be scaled up to mitigate future pandemics on a global scale? “Global mitigation of future pandemic risk must focus on the large scale behaviours that lead to zoonotic spillovers. This approach means engaging with the sectors that drive disease emergence, including industries involved in land-use change, resource extraction, livestock production, travel, and trade, among others” (Lancet Global Health, Volume 3, No. 7, e354-355, 2015) “Large economic development programmes will need health impact assessments that deal explicitly with the risk of emergence of novel diseases, and plans to set up new clinics and surveillance programmes listed as project deliverables.” (Lancet Global Health, Volume 3, No. 7, e354-355, 2015) “An improved understanding of the liability for disease emergence will drive this change; when all are at risk, collective action is needed to strengthen the weakest links in the chain”, (Lancet Global Health, Volume 3, No. 7, e354-355, 2015) APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 59 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Mathematical and Theoretical Biology Institute, 1996 APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 60 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Presidential award for excellence in Sciences, Math and Engineering mentoring, 2011 – Given in recognition to the Mathematical and Theoretical Biology Institute – MTBI APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 61 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft MCMSC Center Renaming Ceremony in Honor of Simon A. Levin APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 62 / 64 Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d Dr aft Grad students and researchers involved in the Ebola research at SAL-MCMSC - all MTBI alumni Dr. Derdei Bichara: Epidemiology, Infectious Diseases Baltazar Espinoza: Epidemiology, Game theory, Economics Diego Chowell: Evolutionary biology, Cancer, Computational modeling Maryam Khan: Epidemiology, Social Sciences, Environment Kamal Barley: Epidemiology, Health disparities APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Dr. Kamuela Yong: Ecology, Diffusion Victor Moreno: Epidemiology, Graph theory Claudia Rodriguez: Math education and policy, Retention of underrepresented students Dr. Edgar Herera Diaz: Epidemiology, Diffusion Dr. Anuj Mubayi: Mathematical Epidemiology, Quantitative Social Sciences Simon A. Levin Modeling Center 63 / 64 Dr aft Overview Big Data Risk factors and recent outbreaks Modeling disease dynamics using a Lagrangian perspective Spatial spread of infectious d APLICACION DEL MODELAMIENTO Carlos Castillo-Chavez Simon A. Levin Modeling Center 64 / 64