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      An open challenge to advance probabilistic forecasting for dengue epidemics

      research-article
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      Proceedings of the National Academy of Sciences of the United States of America
      National Academy of Sciences
      forecast, dengue, epidemic, Peru, Puerto Rico

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          Significance

          Forecasts routinely provide critical information for dangerous weather events but not yet for epidemics. Researchers develop computational models that can be used for infectious disease forecasting, but forecasts have not been broadly compared or tested. We collaboratively compared forecasts from 16 teams for 8 y of dengue epidemics in Peru and Puerto Rico. The comparison highlighted components that forecasts did well (e.g., situational awareness late in the season) and those that need more work (e.g., early season forecasts). It also identified key facets to improve forecasts, including using multiple model ensemble approaches to improve overall forecast skill. Future infectious disease forecasting work can build on these findings and this framework to improve the skill and utility of forecasts.

          Abstract

          A wide range of research has promised new tools for forecasting infectious disease dynamics, but little of that research is currently being applied in practice, because tools do not address key public health needs, do not produce probabilistic forecasts, have not been evaluated on external data, or do not provide sufficient forecast skill to be useful. We developed an open collaborative forecasting challenge to assess probabilistic forecasts for seasonal epidemics of dengue, a major global public health problem. Sixteen teams used a variety of methods and data to generate forecasts for 3 epidemiological targets (peak incidence, the week of the peak, and total incidence) over 8 dengue seasons in Iquitos, Peru and San Juan, Puerto Rico. Forecast skill was highly variable across teams and targets. While numerous forecasts showed high skill for midseason situational awareness, early season skill was low, and skill was generally lowest for high incidence seasons, those for which forecasts would be most valuable. A comparison of modeling approaches revealed that average forecast skill was lower for models including biologically meaningful data and mechanisms and that both multimodel and multiteam ensemble forecasts consistently outperformed individual model forecasts. Leveraging these insights, data, and the forecasting framework will be critical to improve forecast skill and the application of forecasts in real time for epidemic preparedness and response. Moreover, key components of this project—integration with public health needs, a common forecasting framework, shared and standardized data, and open participation—can help advance infectious disease forecasting beyond dengue.

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          Most cited references28

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          A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970–2010

          Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.
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            Interactions between serotypes of dengue highlight epidemiological impact of cross-immunity

            Dengue, a mosquito-borne virus of humans, infects over 50 million people annually. Infection with any of the four dengue serotypes induces protective immunity to that serotype, but does not confer long-term protection against infection by other serotypes. The immunological interactions between serotypes are of central importance in understanding epidemiological dynamics and anticipating the impact of dengue vaccines. We analysed a 38-year time series with 12 197 serotyped dengue infections from a hospital in Bangkok, Thailand. Using novel mechanistic models to represent different hypothesized immune interactions between serotypes, we found strong evidence that infection with dengue provides substantial short-term cross-protection against other serotypes (approx. 1–3 years). This is the first quantitative evidence that short-term cross-protection exists since human experimental infection studies performed in the 1950s. These findings will impact strategies for designing dengue vaccine studies, future multi-strain modelling efforts, and our understanding of evolutionary pressures in multi-strain disease systems.
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              Ecological and immunological determinants of dengue epidemics.

              The management of infectious diseases is an increasingly important public health issue, the effective implementation of which is often complicated by difficulties in teasing apart the relative roles of extrinsic and intrinsic factors influencing transmission. Dengue, a vector-borne strain polymorphic disease, is one such infection where transmission dynamics are affected by environmental variables as well as immune-mediated serotype interactions. To understand how alternative hypotheses concerning dengue infection and transmission may explain observed multiannual cycles in disease incidence, we adopt a theoretical approach that combines both ecological and immunological mechanisms. We demonstrate that, contrary to perceived wisdom, patterns generated solely by antibody-dependent enhancement or heterogeneity in virus virulence are not consistent with serotype-specific notification data in important ways. Furthermore, to generate epidemics with the characteristic signatures observed in data, we find that a combination of seasonal variation in vector demography and, crucially, a short-lived period of cross-immunity is sufficient. We then show how understanding the persistence and eradication of dengue serotypes critically depends on the alternative assumed mechanisms.
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                Author and article information

                Journal
                Proc Natl Acad Sci U S A
                Proc. Natl. Acad. Sci. U.S.A
                pnas
                pnas
                PNAS
                Proceedings of the National Academy of Sciences of the United States of America
                National Academy of Sciences
                0027-8424
                1091-6490
                26 November 2019
                11 November 2019
                11 November 2019
                : 116
                : 48
                : 24268-24274
                Affiliations
                [1] aDivision of Vector-Borne Diseases, Centers for Disease Control and Prevention , San Juan 00920, Puerto Rico;
                [2] bDepartment of Epidemiology, Harvard T. H. Chan School of Public Health , Boston, MA 02115;
                [3] cData Analytics, Areté Associates , Northridge, CA 91324;
                [4] dSystems Integration Branch, Johns Hopkins University Applied Physics Laboratory , Laurel, MD 20723;
                [5] eDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University , New York, NY 10032;
                [6] fData to Decisions Cooperative Research Center , Kent Town, SA 5067, Australia;
                [7] gHeinz College Information System Management, Carnegie Mellon University , Adelaide, SA 5000, Australia;
                [8] hSchool of Computer Science, Carnegie Mellon University , Pittsburgh, PA 15213;
                [9] iDepartment of Statistics, Carnegie Mellon University , Pittsburgh, PA 15213;
                [10] jDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD 21205;
                [11] kDepartment of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts , Amherst, MA 01003;
                [12] lDepartment of Biology, University of Florida , Gainesville, FL 32611;
                [13] mEmerging Pathogens Institute, University of Florida , Gainesville, FL 32611;
                [14] nDepartment of Biological Sciences, University of Notre Dame , Notre Dame, IN 46556;
                [15] oEck Institute for Global Health, University of Notre Dame , Notre Dame, IN 46556;
                [16] pHospital for Tropical Diseases, Oxford University Clinical Research Unit , Ho Chi Minh City, Vietnam;
                [17] qDepartment of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine , London WC1E 7HT, United Kingdom;
                [18] rClimate and Health Program, Barcelona Institute for Global Health , 08003 Barcelona, Spain;
                [19] sCollege of Engineering, Mathematics and Physical Sciences, University of Exeter , Exeter EX4 4QF, United Kingdom;
                [20] tPredictia Intelligent Data Solutions , 39005 Santander, Spain;
                [21] uScientific Computation Program, Oswaldo Cruz Foundation , Rio de Janeiro 21040-900, Brazil;
                [22] vCatalan Institution for Research and Advanced Studies , 08010 Barcelona, Spain;
                [23] wDepartment of Mathematical Biology, Indian Statistical Institute, Kolkata, India 700108;
                [24] xPasteur Kyoto International Joint Research Unit for Integrative Vaccinomics , 606-8501 Kyoto, Japan;
                [25] yDepartment of Global Health, Centre National de la Recherche Scientifique , 75016 Paris, France;
                [26] zDepartment of Mathematics and Statistics, Mount Holyoke College , South Hadley, MA 01075;
                [27] aaRAND Corporation, Santa Monica CA 90401;
                [28] bbOpen Philanthropy , San Francisco, CA 94105;
                [29] ccDepartment of Computer Science and Software Engineering , Miami University, Oxford, OH 45056;
                [30] ddF. I. Proctor Foundation for Research in Ophthalmology, University of California , San Francisco, CA 94122;
                [31] eeInformation Science and Technology, Hokkaido University , Sapporo 060-0808, Japan;
                [32] ffDivision of Environmental Health Sciences, School of Public Health, University of Minnesota , Twin Cities, MN 55455;
                [33] ggVectorAnalytica, Washington, DC 20007;
                [34] hhDepartment of Aeronautical Engineering , Universidade de Sao Paolo, Sao Paolo 13566-590, Brazil;
                [35] iiDepartment of Philosophy, University of Miami , Coral Gables, FL 33146;
                [36] jjDepartment of Statistics, Virginia Tech , Blacksburg, VA 24060;
                [37] kkIntegrative Biology, University of South Florida , Tampa, FL 33620;
                [38] llDepartment of Biology, Stanford University , Stanford, CA 94305;
                [39] mmInfectious Diseases, College of Veterinary Medicine, University of Georgia, Athens , GA 30602;
                [40] nnOdum School of Ecology, University of Georgia , Athens, GA 30602;
                [41] ooDepartment of Geography, University of Florida , Gainesville, FL 32608;
                [42] ppSchool of Life Sciences, University of KwaZulu , Natal 3629, South Africa;
                [43] qqDepartment of Medicine, State University of New York Upstate Medical University , Syracuse, NY 13421;
                [44] rrDepartment of Biostatistics, University of Michigan , Ann Arbor, MI 48109;
                [45] ssDepartment of Civil and Environmental Engineering, West Virginia University , Morgantown, WV 26505;
                [46] ttDepartment of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742;
                [47] uuPuerto Rico Department of Health , San Juan 00927, Puerto Rico;
                [48] vvDepartment of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California , Davis, CA 95616;
                [49] wwDepartment of Environmental, Agricultural, and Occupational Health, College of Public Health, University of Nebraska Medical Center , Omaha, NE 68198;
                [50] xxInfluenza Division, Centers for Disease Control and Prevention , Atlanta, GA 30329;
                [51] yyArmed Forces Health Surveillance Branch, Department of Defense , Silver Spring, MD 20904;
                [52] zzClimate Program Office, National Oceanic and Atmospheric Administration , Silver Spring, MD 20910;
                [53] aaaLeidos supporting the Biomedical Advanced Research and Development Authority, Department of Health and Human Services , Washington, DC 20201;
                [54] bbbBureau of Oceans, International Environmental and Scientific Affairs , US Department of State, Washington, DC 20520;
                [55] cccOffice of Science and Technology Policy , The White House, Washington, DC 20502;
                [56] dddBNext, In-Q-Tel, Arlington , VA 22201
                Author notes
                1To whom correspondence may be addressed. Email: mjohansson@ 123456cdc.gov .

                Edited by Simon A. Levin, Princeton University, Princeton, NJ, and approved September 30, 2019 (received for review June 18, 2019)

                Author contributions: M.A.J., B.R.-G., C.M.B., M.B., D.S., L.M.-y.T.-R., B.M.F., J.T., J.A., M.C., H.S.M., A.M.H., D.G., and J.-P.C. designed research; M.A.J., K.M.A., S.D., J.D., A.L.B., B.B., L.J.M., S.M.B., E.G., T.K.Y., J.S., T.M., N.L., A.L., G.O., G.J., L.C.B., D.C.F., S.H., R.J.T., R.R., J.L., N.G.R., D.A.T.C., S.A.L., S.M.M., H.E.C., R.L., T.C.B., M.G.-D., M.S.C., X.R., T.S., R.P., E.L.R., K.S., A.C.B., X.M., O.O., R.V., D.M., M.M., D.M.R., T.C.P., S.A., F.L., L.W., M.C., Y.L., A.R., E.O., J.R., H.B., A. Juarrero, L.R.J., R.B.G., J.M.C., E.A.M., C.C.M., J.R.R, S.J.R., A.M.S.-I., D.P.W., A. Jutla, R.K., M.P., and R.R.C. performed research; M.A.J., K.M.A., S.D., J.D., A.L.B., B.B., L.J.M., T.B., S.M.B., E.G., T.K.Y., J.S., T.M., N.L., A.L., G.O., G.J., L.C.B., D.C.F., S.H., R.J.T., R.R., J.L., N.G.R., D.A.T.C., S.A.L., S.M.M., H.E.C., R.L., T.C.B., M.G.-D., M.S.C., X.R., T.S., R.P., E.L.R., K.S., A.C.B., X.M., O.O., R.V., D.M., M.M., D.M.R., T.C.P., S.A., F.L., L.W., M.C., Y.L., A.R., E.O., J.R., H.B., A. Juarrero, L.R.J., R.B.G., J.M.C., E.A.M., C.C.M., J.R.R., S.J.R., A.M.S.-I., D.P.W., A. Jutla, R.K., M.P., R.R.C., and J.E.B. contributed new reagents/analytic tools; M.A.J., T.B., L.M.-y.-T.-R., B.M.F., J.A., and M.C. analyzed data; and M.A.J., K.M.A., A.L.B., T.K.Y., T.M., L.C.B., J.L., R.L., X.R., E.L.R., O.O., D.M.R., T.C.P., M.C., E.O., L.R.J., A. Jutla, B.R.-G., C.M.B., J.E.B., M.B., D.S., L.M.-y.-T.-R., B.M.F., J.T., J.A., M.C., H.S.M., A.M.H., D.G., and J.-P.C. wrote the paper.

                Author information
                http://orcid.org/0000-0002-5090-7722
                http://orcid.org/0000-0002-9741-8109
                http://orcid.org/0000-0003-3503-9899
                http://orcid.org/0000-0002-9437-1907
                http://orcid.org/0000-0003-2948-630X
                http://orcid.org/0000-0002-2531-161X
                http://orcid.org/0000-0003-3939-7343
                http://orcid.org/0000-0002-9566-0284
                http://orcid.org/0000-0003-4843-6180
                http://orcid.org/0000-0003-4035-0243
                http://orcid.org/0000-0003-2046-9415
                http://orcid.org/0000-0001-8599-8380
                http://orcid.org/0000-0001-9611-9150
                http://orcid.org/0000-0002-4402-5547
                http://orcid.org/0000-0002-4308-6321
                http://orcid.org/0000-0001-8143-6823
                Article
                201909865
                10.1073/pnas.1909865116
                6883829
                31712420
                2306d1dd-9815-4059-adeb-b35493a90b32
                Copyright © 2019 the Author(s). Published by PNAS.

                This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

                History
                Page count
                Pages: 7
                Funding
                Funded by: HHS | NIH | National Institute of General Medical Sciences (NIGMS) 100000057
                Award ID: GM088491
                Award Recipient : Teresa K Yamana Award Recipient : Jeffrey Shaman Award Recipient : Logan Brooks Award Recipient : David Farrow Award Recipient : Sangwon Hyun Award Recipient : Ryan Joseph Tibshirani Award Recipient : Roni Rosenfeld Award Recipient : Nicholas G. Reich Award Recipient : Evan L Ray Award Recipient : Krzysztof Sakrejda Award Recipient : Alexandria C Brown Award Recipient : Xi Meng Award Recipient : Travis C Porco Award Recipient : Lee Worden
                Funded by: HHS | NIH | National Institute of General Medical Sciences (NIGMS) 100000057
                Award ID: GM110748
                Award Recipient : Teresa K Yamana Award Recipient : Jeffrey Shaman Award Recipient : Logan Brooks Award Recipient : David Farrow Award Recipient : Sangwon Hyun Award Recipient : Ryan Joseph Tibshirani Award Recipient : Roni Rosenfeld Award Recipient : Nicholas G. Reich Award Recipient : Evan L Ray Award Recipient : Krzysztof Sakrejda Award Recipient : Alexandria C Brown Award Recipient : Xi Meng Award Recipient : Travis C Porco Award Recipient : Lee Worden
                Funded by: DOD | Defense Threat Reduction Agency (DTRA) 100000774
                Award ID: HDTRA1- 15-C-0018
                Award Recipient : Teresa K Yamana Award Recipient : Jeffrey Shaman
                Funded by: National Science Foundation (NSF) 100000001
                Award ID: DGE-1252522
                Award Recipient : Logan Brooks Award Recipient : David Farrow Award Recipient : Sangwon Hyun Award Recipient : Ryan Joseph Tibshirani Award Recipient : Roni Rosenfeld
                Funded by: HHS | National Institutes of Health (NIH) 100000002
                Award ID: EB009403
                Award Recipient : David Farrow Award Recipient : Leah R Johnson Award Recipient : Robert B Gramacy Award Recipient : Jeremy M. Cohen Award Recipient : Erin A. Mordecai Award Recipient : Courtney C. Murdock Award Recipient : Jason R. Rohr Award Recipient : Sadie J Ryan Award Recipient : Anna Stewart Ibarra Award Recipient : Daniel P Weikel
                Funded by: National Science Foundation (NSF) 100000001
                Award ID: DMS-1309174
                Award Recipient : Logan Brooks Award Recipient : David Farrow Award Recipient : Sangwon Hyun Award Recipient : Ryan Joseph Tibshirani Award Recipient : Roni Rosenfeld
                Funded by: HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 100000060
                Award ID: AI102939
                Award Recipient : Justin Lessler Award Recipient : Nicholas G. Reich Award Recipient : Derek A.T. Cummings Award Recipient : Stephen A Lauer Award Recipient : Sean M Moore Award Recipient : Hannah E. Clapham
                Funded by: Royal Society 501100000288
                Award ID: Dorothy Hodgkin Fellowship
                Award Recipient : Rachel Lowe
                Funded by: HHS | NIH | National Institute of General Medical Sciences (NIGMS) 100000057
                Award ID: R21AI115173
                Award ID: R01AI102939
                Award ID: R35GM119582
                Award Recipient : Teresa K Yamana Award Recipient : Jeffrey Shaman Award Recipient : Logan Brooks Award Recipient : David Farrow Award Recipient : Sangwon Hyun Award Recipient : Ryan Joseph Tibshirani Award Recipient : Roni Rosenfeld Award Recipient : Nicholas G. Reich Award Recipient : Evan L Ray Award Recipient : Krzysztof Sakrejda Award Recipient : Alexandria C Brown Award Recipient : Xi Meng Award Recipient : Travis C Porco Award Recipient : Lee Worden
                Funded by: HHS | NIH | National Institute of General Medical Sciences (NIGMS) 100000057
                Award ID: GM087728
                Award Recipient : Teresa K Yamana Award Recipient : Jeffrey Shaman Award Recipient : Logan Brooks Award Recipient : David Farrow Award Recipient : Sangwon Hyun Award Recipient : Ryan Joseph Tibshirani Award Recipient : Roni Rosenfeld Award Recipient : Nicholas G. Reich Award Recipient : Evan L Ray Award Recipient : Krzysztof Sakrejda Award Recipient : Alexandria C Brown Award Recipient : Xi Meng Award Recipient : Travis C Porco Award Recipient : Lee Worden
                Funded by: HHS | National Institutes of Health (NIH) 100000002
                Award ID: AI122284
                Award Recipient : David Farrow Award Recipient : Leah R Johnson Award Recipient : Robert B Gramacy Award Recipient : Jeremy M. Cohen Award Recipient : Erin A. Mordecai Award Recipient : Courtney C. Murdock Award Recipient : Jason R. Rohr Award Recipient : Sadie J Ryan Award Recipient : Anna Stewart Ibarra Award Recipient : Daniel P Weikel
                Categories
                Biological Sciences
                Medical Sciences

                forecast,dengue,epidemic,peru,puerto rico
                forecast, dengue, epidemic, peru, puerto rico

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