Detecting critical slowing down in high-dimensional epidemiological systems

Despite medical advances, the emergence and re-emergence of infectious diseases continue to pose a public health threat. Low-dimensional epidemiological models predict that epidemic transitions are preceded by the phenomenon of critical slowing down (CSD). This has raised the possibility of anticipating disease (re-)emergence using CSD-based early-warning signals (EWS), which are statistical moments estimated from time series data. For EWS to be useful at detecting future (re-)emergence, CSD needs to be a generic (model-independent) feature of epidemiological dynamics irrespective of system complexity. Currently, it is unclear whether the predictions of CSD—derived from simple, low-dimensional systems—pertain to real systems, which are high-dimensional. To assess the generality of CSD, we carried out a simulation study of a hierarchy of models, with increasing structural complexity and dimensionality, for a measles-like infectious disease. Our five models included: i) a nonseasonal homogeneous Susceptible-Exposed-Infectious-Recovered (SEIR) model, ii) a homogeneous SEIR model with seasonality in transmission, iii) an age-structured SEIR model, iv) a multiplex network-based model (Mplex) and v) an agent-based simulator (FRED). All models were parameterised to have a herd-immunity immunization threshold of around 90% coverage, and underwent a linear decrease in vaccine uptake, from 92% to 70% over 15 years. We found evidence of CSD prior to disease re-emergence in all models. We also evaluated the performance of seven EWS: the autocorrelation, coefficient of variation, index of dispersion, kurtosis, mean, skewness, variance. Performance was scored using the Area Under the ROC Curve (AUC) statistic. The best performing EWS were the mean and variance, with AUC > 0.75 one year before the estimated transition time. These two, along with the autocorrelation and index of dispersion, are promising candidate EWS for detecting disease emergence.

[1]  Rustom Antia,et al.  The role of evolution in the emergence of infectious diseases , 2003, Nature.

[2]  M. Rietkerk,et al.  Spatial vegetation patterns and imminent desertification in Mediterranean arid ecosystems , 2007, Nature.

[3]  Shawn T. Brown,et al.  The Role of Subway Travel in an Influenza Epidemic: A New York City Simulation , 2011, Journal of Urban Health.

[4]  Aravind Srinivasan,et al.  Modelling disease outbreaks in realistic urban social networks , 2004, Nature.

[5]  John M. Drake,et al.  Leading indicators of mosquito-borne disease elimination , 2015, Theoretical Ecology.

[6]  John M. Drake,et al.  Theory of early warning signals of disease emergenceand leading indicators of elimination , 2013, Theoretical Ecology.

[7]  S. Merler,et al.  Deciphering the relative weights of demographic transition and vaccination in the decrease of measles incidence in Italy , 2014, Proceedings of the Royal Society B: Biological Sciences.

[8]  P. Hohenberg,et al.  Theory of Dynamic Critical Phenomena , 1977 .

[9]  Pejman Rohani,et al.  Combating pertussis resurgence: One booster vaccination schedule does not fit all , 2015, Proceedings of the National Academy of Sciences.

[10]  Charles T Perretti,et al.  Regime shift indicators fail under noise levels commonly observed in ecological systems. , 2012, Ecological applications : a publication of the Ecological Society of America.

[11]  Derin B. Wysham,et al.  Regime shifts in ecological systems can occur with no warning. , 2010, Ecology letters.

[12]  David K. Smith,et al.  The genesis and source of the H7N9 influenza viruses causing human infections in China , 2013, Nature.

[13]  Matthew J. Ferrari,et al.  Characterizing the impact of spatial clustering of susceptibility for measles elimination , 2019, Vaccine.

[14]  R. Mikolajczyk,et al.  Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases , 2008, PLoS medicine.

[15]  D. E. Barton,et al.  The Elements of Stochastic Processes with Applications to the Natural Sciences , 1964 .

[16]  James O. Lloyd-Smith,et al.  Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting , 2016, Science.

[17]  Paige B. Miller,et al.  Forecasting infectious disease emergence subject to seasonal forcing , 2017, Theoretical Biology and Medical Modelling.

[18]  S. Carpenter,et al.  Early-warning signals for critical transitions , 2009, Nature.

[19]  A. McKane,et al.  Stochastic formulation of ecological models and their applications. , 2012, Trends in ecology & evolution.

[20]  R. Webster,et al.  Are We Ready for Pandemic Influenza? , 2003, Science.

[21]  M. Scheffer,et al.  Slowing Down in Spatially Patterned Ecosystems at the Brink of Collapse , 2011, The American Naturalist.

[22]  A. Fauci,et al.  The challenge of emerging and re-emerging infectious diseases , 2004, Nature.

[23]  N. Grassly,et al.  Mathematical models of infectious disease transmission , 2008, Nature Reviews Microbiology.

[24]  John Salvatier,et al.  Probabilistic programming in Python using PyMC3 , 2016, PeerJ Comput. Sci..

[25]  Shawn T. Brown,et al.  FRED (A Framework for Reconstructing Epidemic Dynamics): an open-source software system for modeling infectious diseases and control strategies using census-based populations , 2013, BMC Public Health.

[26]  Andrew Gelman,et al.  The No-U-turn sampler: adaptively setting path lengths in Hamiltonian Monte Carlo , 2011, J. Mach. Learn. Res..

[27]  D. Lathrop Nonlinear Dynamics and Chaos: With Applications to Physics, Biology, Chemistry, and Engineering , 2015 .

[28]  R. Leggiadro,et al.  Outbreaks in a Rapidly Changing Central Africa , 2019, Pediatric Infectious Disease Journal.

[29]  Lei Dai,et al.  Generic Indicators for Loss of Resilience Before a Tipping Point Leading to Population Collapse , 2012, Science.

[30]  Alessandro Vespignani,et al.  Measurability of the epidemic reproduction number in data-driven contact networks , 2018, Proceedings of the National Academy of Sciences.

[31]  S. Omer,et al.  Vaccine Refusal, Mandatory Immunization, and the Risks of Vaccine-Preventable Diseases , 2010 .

[32]  Trevor Hastie,et al.  The Elements of Statistical Learning , 2001 .

[33]  Ottar N. Bjørnstad,et al.  The impact of specialized enemies on the dimensionality of host dynamics , 2001, Nature.

[34]  Leah R Johnson,et al.  Detecting the impact of temperature on transmission of Zika, dengue, and chikungunya using mechanistic models , 2017, PLoS neglected tropical diseases.

[35]  Alessandro Vespignani,et al.  Inferring the Structure of Social Contacts from Demographic Data in the Analysis of Infectious Diseases Spread , 2012, PLoS Comput. Biol..

[36]  M. Keeling,et al.  Modeling Infectious Diseases in Humans and Animals , 2007 .

[37]  S. Carpenter,et al.  Early Warnings of Regime Shifts: A Whole-Ecosystem Experiment , 2011, Science.

[38]  Alessandro Vespignani,et al.  Comparing large-scale computational approaches to epidemic modeling: Agent-based versus structured metapopulation models , 2010, BMC infectious diseases.

[39]  Éric Marty,et al.  Anticipating epidemic transitions with imperfect data , 2018, PLoS Comput. Biol..

[40]  A. King,et al.  The impact of past vaccination coverage and immunity on pertussis resurgence , 2018, Science Translational Medicine.

[41]  P. Kaye Infectious diseases of humans: Dynamics and control , 1993 .

[42]  Alessandro Vespignani,et al.  Spatiotemporal dynamics of the Ebola epidemic in Guinea and implications for vaccination and disease elimination: a computational modeling analysis , 2016, BMC Medicine.

[43]  John M Drake,et al.  Anticipating the emergence of infectious diseases , 2017, Journal of The Royal Society Interface.

[44]  J. Drake,et al.  Early warning signals of extinction in deteriorating environments , 2010, Nature.

[45]  W. Ebeling Stochastic Processes in Physics and Chemistry , 1995 .

[46]  Eric R. Ziegel,et al.  The Elements of Statistical Learning , 2003, Technometrics.

[47]  C. Kuehn Multiple Time Scale Dynamics , 2015 .

[48]  Lennart Martens,et al.  Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins , 2018, Scientific Reports.

[49]  W. Team Ebola Virus Disease in West Africa — The First 9 Months of the Epidemic and Forward Projections , 2014 .

[50]  John M Drake,et al.  Disentangling reporting and disease transmission , 2017, Theoretical Ecology.

[51]  Mary E. Wilson,et al.  Travel and the emergence of infectious diseases. , 1995, Emerging infectious diseases.

[52]  M. Lässig,et al.  A predictive fitness model for influenza , 2014, Nature.

[53]  S. Merler,et al.  The role of different social contexts in shaping influenza transmission during the 2009 pandemic , 2014, Scientific Reports.

[54]  Peter Svedlindh,et al.  Dynamics of an Interacting Particle System: Evidence of Critical Slowing Down , 1997 .

[55]  O. Diekmann,et al.  On the definition and the computation of the basic reproduction ratio R0 in models for infectious diseases in heterogeneous populations , 1990, Journal of mathematical biology.

[56]  Norman T. J. Bailey The Elements of Stochastic Processes with Applications to the Natural Sciences , 1964 .

[57]  M. Scheffer,et al.  Slowing down as an early warning signal for abrupt climate change , 2008, Proceedings of the National Academy of Sciences.

[58]  Stefano Merler,et al.  An individual-based model of hepatitis A transmission. , 2009, Journal of theoretical biology.

[59]  Michael A. Gibson,et al.  Efficient Exact Stochastic Simulation of Chemical Systems with Many Species and Many Channels , 2000 .

[60]  Maria E. Sundaram,et al.  The True Cost of Measles Outbreaks During the Postelimination Era , 2019, JAMA.

[61]  N. Kampen,et al.  Stochastic processes in physics and chemistry , 1981 .

[62]  Mikiko Senga,et al.  Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections. , 2014, The New England journal of medicine.

[63]  Tom Fawcett,et al.  An introduction to ROC analysis , 2006, Pattern Recognit. Lett..

[64]  Pejman Rohani,et al.  Epidemiological Consequences of Imperfect Vaccines for Immunizing Infections , 2014, SIAM J. Appl. Math..