Explorer Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H 3 N 2

Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control. Citation: Lemey P, Rambaut A, Bedford T, Faria N, Bielejec F, et al. (2014) Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2. PLoS Pathog 10(2): e1003932. doi:10.1371/journal.ppat. 1003932 Editor: Neil M. Ferguson, Imperial College London, United Kingdom Received October 21, 2013; Accepted January 2, 2014; Published February 20, 2014 Copyright: 2014 Lemey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The research leading to these results has received funding from the European Union Seventh Framework Programme [FP7/2007–2013] under Grant Agreement no. 278433-PREDEMICS and ERC Grant agreement no. 260864. MAS is in part supported by NSF grant DMS 1264153 and NIH grants R01 AI107034 and R01 HG006139. Collaboration between MAS, AR and PL was supported by the National Evolutionary Synthesis Center (NESCent), NSF EF-0423641. This work was supported by the Wellcome Trust [092807] to AR. TB is supported by the Royal Society. DJS and CAR acknowledge EU FP7 programs EMPERIE (223498) and ANTIGONE (278976), Human Frontier Science Program (HFSP) program grant P0050/2008, Wellcome 087982AIA, NIH Director’s Pioneer Award DP1-OD000490-01 and National Institute of Allergy and Infectious Diseases NIH CEIRS contract HHSN266200700010C. CAR was supported by a University Research Fellowship from the Royal Society. Further, research was partially completed while PL and MAS were visiting the Institute for Mathematical Sciences, National University of Singapore in 2011. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: philippe.lemey@rega.kuleuven. be