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Virus genomes reveal the factors that spread and sustained the West African Ebola epidemic

Gytis Dudas, Luiz Max Carvalho, Trevor Bedford, Andrew J. Tatem, Guy Baele, Nuno Faria, Daniel J. Park, Jason Ladner, Armando Arias, Danny Asogun, Filip Bielejec, Sarah Caddy, Matt Cotten, Jonathan Dambrozio, Simon Dellicour, Antonino Di Caro, Joseph W. Diclaro II, Sophie Duraffour, Mike Elmore, Lawrence Fakoli, Merle Gilbert, Sahr M Gevao, Stephen Gire, Adrianne Gladden-Young, Andreas Gnirke, Augustine Goba, Donald S. Grant, Bart Haagmans, Julian A. Hiscox, Umaru Jah, Brima Kargbo, Jeffrey Kugelman, Di Liu, Jia Lu, Christine M. Malboeuf, Suzanne Mate, David A. Matthews, Christian B. Matranga, Luke Meredith, James Qu, Joshua Quick, Susan D. Pas, My VT Phan, Georgios Poliakis, Chantal Reusken, Mariano Sanchez-Lockhart, Stephen F. Schaffner, John S. Schieffelin, Rachel S. Sealfon, Etienne Simon-Loriere, Saskia L. Smits, Kilian Stoecker, Lucy Thorne, Ekaete A. Tobin, Mohamed A. Vandi, Simon J. Watson, Kendra West, Shannon Whitmer, Michael R. Wiley, Sarah M. Winnicki, Shirlee Wohl, Roman Wölfel, Nathan L. Yozwiak, Kristian G. Andersen, Sylvia Blyden, Fatorma Bolay, Miles Carroll, Boubacar Diallo, Pierre Formenty, Christophe Fraser, George F. Gao, Robert F. Garry, Ian Goodfellow, Stephan Günther, Christian Happi, Edward C Holmes, Brima Kargbo, Paul Kellam, Marion P. G. Koopmans, Nicholas J. Loman, N’Faly Magassouba, Dhamari Naidoo, Stuart T. Nichol, Tolbert Nyenswah, Gustavo Palacios, Oliver G Pybus, Pardis Sabeti, Amadou Sall, Ute Ströher, Isatta Wury, Marc A Suchard, Philippe Lemey, Andrew Rambaut
doi: https://doi.org/10.1101/071779
Gytis Dudas
1Institute of Evolutionary Biology, University of Edinburgh, King’s Buildings, Edinburgh, EH9 3FL, UK
2Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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  • For correspondence: a.rambaut@ed.ac.uk gdudas@fredhutch.org philippe.lemey@rega.kuleuven.be
Luiz Max Carvalho
1Institute of Evolutionary Biology, University of Edinburgh, King’s Buildings, Edinburgh, EH9 3FL, UK
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Trevor Bedford
2Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Andrew J. Tatem
3WorldPop, Department of Geography and Environment, University of Southampton, Highfield, Southampton SO17 1BJ, UK
4Flowminder Foundation, Stockholm, Sweden
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Guy Baele
5Department of Microbiology and Immunology, Rega Institute, KU Leuven University of Leuven, Leuven, Belgium
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Nuno Faria
6Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK
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Daniel J. Park
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Jason Ladner
8Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
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Armando Arias
9Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK
10Section for Virology, National Veterinary Institute, Technical University of Denmark, Blowsvej 27, 1870, Frederiksberg C, Denmark
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Danny Asogun
11Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria
12The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
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Filip Bielejec
5Department of Microbiology and Immunology, Rega Institute, KU Leuven University of Leuven, Leuven, Belgium
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Sarah Caddy
9Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK
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Matt Cotten
13Virus Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
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Jonathan Dambrozio
8Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
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Simon Dellicour
5Department of Microbiology and Immunology, Rega Institute, KU Leuven University of Leuven, Leuven, Belgium
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Antonino Di Caro
14National Institute for Infectious Diseases “L. Spallanzani” - IRCCS, Via Portuense 292, 00149 Rome, Italy
12The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
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Joseph W. Diclaro II
15Naval Medical Research Unit 3, 3A Imtidad Ramses Street, Cairo, 11517, Egypt
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Sophie Duraffour
16Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
12The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
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Mike Elmore
17National Infections Service, Public Health England, Porton Down, Salisbury, Wilts SP4 0JG, UK
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Lawrence Fakoli
18Liberian Institute for Biomedical Research, Charlesville, Liberia.
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Merle Gilbert
8Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
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Sahr M Gevao
19University of Sierra Leone, Freetown, Sierra Leone
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Stephen Gire
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
20Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
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Adrianne Gladden-Young
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Andreas Gnirke
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Augustine Goba
21Viral Hemorrhagic Fever Program, Kenema Government Hospital, 1 Combema Road, Kenema, Sierra Leone
22Ministry of Health and Sanitation, 4th Floor Youyi Building, Freetown, Sierra Leone
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Donald S. Grant
21Viral Hemorrhagic Fever Program, Kenema Government Hospital, 1 Combema Road, Kenema, Sierra Leone
22Ministry of Health and Sanitation, 4th Floor Youyi Building, Freetown, Sierra Leone
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Bart Haagmans
23Department of Viroscience, Erasmus University Medical Centre, P.O. Box 20140, 300 CA Rotterdam, the Netherlands
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Julian A. Hiscox
24Institute of Infection and Global Health, University of Liverpool, Liverpool L69 2BE, United Kingdom
25NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, UK.
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Umaru Jah
26University of Makeni, Makeni, Sierra Leone
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Brima Kargbo
22Ministry of Health and Sanitation, 4th Floor Youyi Building, Freetown, Sierra Leone
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Jeffrey Kugelman
8Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
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Di Liu
27Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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Jia Lu
9Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK
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Christine M. Malboeuf
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Suzanne Mate
8Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
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David A. Matthews
28University of Bristol, BS8 1TD, United Kingdom
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Christian B. Matranga
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Luke Meredith
9Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK
26University of Makeni, Makeni, Sierra Leone
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James Qu
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Joshua Quick
29Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
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Susan D. Pas
23Department of Viroscience, Erasmus University Medical Centre, P.O. Box 20140, 300 CA Rotterdam, the Netherlands
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My VT Phan
13Virus Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
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Georgios Poliakis
24Institute of Infection and Global Health, University of Liverpool, Liverpool L69 2BE, United Kingdom
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Chantal Reusken
23Department of Viroscience, Erasmus University Medical Centre, P.O. Box 20140, 300 CA Rotterdam, the Netherlands
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Mariano Sanchez-Lockhart
8Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
30University of Nebraska Medical Center, Omaha, NE, USA
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Stephen F. Schaffner
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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John S. Schieffelin
31Department of Pediatrics, Section of Infectious Diseases, New Orleans, LA 70112, USA
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Rachel S. Sealfon
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Etienne Simon-Loriere
32Institut Pasteur, Functional Genetics of Infectious Diseases Unit, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
33CNRS URA3012, Paris 75015, France
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Saskia L. Smits
23Department of Viroscience, Erasmus University Medical Centre, P.O. Box 20140, 300 CA Rotterdam, the Netherlands
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Kilian Stoecker
34Bundeswehr Institute of Microbiology, Neuherbergstrasse 11, 80937 Munich, Germany
12The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
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Lucy Thorne
9Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK
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Ekaete A. Tobin
11Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria
12The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
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Mohamed A. Vandi
21Viral Hemorrhagic Fever Program, Kenema Government Hospital, 1 Combema Road, Kenema, Sierra Leone
22Ministry of Health and Sanitation, 4th Floor Youyi Building, Freetown, Sierra Leone
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Simon J. Watson
13Virus Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
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Kendra West
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Shannon Whitmer
35Viral Special Pathogens Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Atlanta, Georgia, USA
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Michael R. Wiley
8Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
30University of Nebraska Medical Center, Omaha, NE, USA
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Sarah M. Winnicki
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
20Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
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Shirlee Wohl
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
20Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
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Roman Wölfel
34Bundeswehr Institute of Microbiology, Neuherbergstrasse 11, 80937 Munich, Germany
12The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
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Nathan L. Yozwiak
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
20Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
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Kristian G. Andersen
36The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA.
37Scripps Translational Science Institute, La Jolla, CA 92037, USA
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
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Sylvia Blyden
22Ministry of Health and Sanitation, 4th Floor Youyi Building, Freetown, Sierra Leone
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Fatorma Bolay
18Liberian Institute for Biomedical Research, Charlesville, Liberia.
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Miles Carroll
17National Infections Service, Public Health England, Porton Down, Salisbury, Wilts SP4 0JG, UK
12The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
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Boubacar Diallo
39World Health Organization, Conakry, Guinea
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Pierre Formenty
40WHO Ebola Response Team
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Christophe Fraser
41Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analyses and Modelling, School of Public Health, Imperial College London, UK
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George F. Gao
27Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
42Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China
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Robert F. Garry
43Department of Microbiology & Immunology, New Orleans, LA 70112, USA
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Ian Goodfellow
9Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK
26University of Makeni, Makeni, Sierra Leone
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Stephan Günther
16Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
12The European Mobile Laboratory Consortium, 20359 Hamburg, Germany
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Christian Happi
44Redeemer’s University, Ede, Osun State, Nigeria
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Edward C Holmes
45Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, the University of Sydney, Sydney, NSW 2006, Australia
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Brima Kargbo
22Ministry of Health and Sanitation, 4th Floor Youyi Building, Freetown, Sierra Leone
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Paul Kellam
13Virus Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
47Division of Infectious Diseases, Imperial College Faculty of Medicine, London W2 1PG, UK
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Marion P. G. Koopmans
23Department of Viroscience, Erasmus University Medical Centre, P.O. Box 20140, 300 CA Rotterdam, the Netherlands
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Nicholas J. Loman
29Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
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N’Faly Magassouba
48Universit Gamal Abdel Nasser de Conakry, Laboratoire des Fivres Hmorragiques en Guine, Conakry, Guinea
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Dhamari Naidoo
40WHO Ebola Response Team
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Stuart T. Nichol
35Viral Special Pathogens Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Atlanta, Georgia, USA
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Tolbert Nyenswah
38Minstry of Health Liberia, Monrovia, Liberia
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Gustavo Palacios
8Center for Genome Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA
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Oliver G Pybus
6Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK
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Pardis Sabeti
7Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA
20Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
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Amadou Sall
32Institut Pasteur, Functional Genetics of Infectious Diseases Unit, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
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Ute Ströher
35Viral Special Pathogens Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Atlanta, Georgia, USA
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Isatta Wury
46Ministry of Health Guinea, Conakry, Guinea
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Marc A Suchard
49Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, CA, USA
50Department of Biomathematics David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA
51Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA
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Philippe Lemey
5Department of Microbiology and Immunology, Rega Institute, KU Leuven University of Leuven, Leuven, Belgium
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  • For correspondence: a.rambaut@ed.ac.uk gdudas@fredhutch.org philippe.lemey@rega.kuleuven.be
Andrew Rambaut
1Institute of Evolutionary Biology, University of Edinburgh, King’s Buildings, Edinburgh, EH9 3FL, UK
52Centre for Immunology, Infection and Evolution, University of Edinburgh, King’s Buildings, Edinburgh, EH9 3FL, UK
53Fogarty International Center, National Institutes of Health, Bethesda, MD, USA
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  • For correspondence: a.rambaut@ed.ac.uk gdudas@fredhutch.org philippe.lemey@rega.kuleuven.be
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Summary

The 2013-2016 epidemic of Ebola virus disease in West Africa was of unprecedented magnitude, duration and impact. Extensive collaborative sequencing projects have produced a large collection of over 1600 Ebola virus genomes, representing over 5% of known cases, unmatched for any single human epidemic. In a comprehensive analysis of this entire dataset, we reconstruct in detail the history of migration, proliferation and decline of Ebola virus throughout the region. We test the association of geography, climate, administrative boundaries, demography and culture with viral movement among 56 administrative regions. Our results show that during the outbreak viral lineages moved according to a classic ‘gravity’ model, with more intense migration between larger and more proximate population centers. Despite a strong attenuation of international dispersal after border closures, localized cross-border transmission beforehand had already set the seeds for an international epidemic, rendering these measures relatively ineffective in curbing the epidemic. We use this empirical evidence to address why the epidemic did not spread into neighboring countries, showing that although these regions were susceptible to developing significant outbreaks, they were also at lower risk of viral introductions. Finally, viral genome sequence data uniquely reveals this large epidemic to be a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help inform approaches to intervention in such epidemics in the future.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Virus genomes reveal the factors that spread and sustained the West African Ebola epidemic
Gytis Dudas, Luiz Max Carvalho, Trevor Bedford, Andrew J. Tatem, Guy Baele, Nuno Faria, Daniel J. Park, Jason Ladner, Armando Arias, Danny Asogun, Filip Bielejec, Sarah Caddy, Matt Cotten, Jonathan Dambrozio, Simon Dellicour, Antonino Di Caro, Joseph W. Diclaro II, Sophie Duraffour, Mike Elmore, Lawrence Fakoli, Merle Gilbert, Sahr M Gevao, Stephen Gire, Adrianne Gladden-Young, Andreas Gnirke, Augustine Goba, Donald S. Grant, Bart Haagmans, Julian A. Hiscox, Umaru Jah, Brima Kargbo, Jeffrey Kugelman, Di Liu, Jia Lu, Christine M. Malboeuf, Suzanne Mate, David A. Matthews, Christian B. Matranga, Luke Meredith, James Qu, Joshua Quick, Susan D. Pas, My VT Phan, Georgios Poliakis, Chantal Reusken, Mariano Sanchez-Lockhart, Stephen F. Schaffner, John S. Schieffelin, Rachel S. Sealfon, Etienne Simon-Loriere, Saskia L. Smits, Kilian Stoecker, Lucy Thorne, Ekaete A. Tobin, Mohamed A. Vandi, Simon J. Watson, Kendra West, Shannon Whitmer, Michael R. Wiley, Sarah M. Winnicki, Shirlee Wohl, Roman Wölfel, Nathan L. Yozwiak, Kristian G. Andersen, Sylvia Blyden, Fatorma Bolay, Miles Carroll, Boubacar Diallo, Pierre Formenty, Christophe Fraser, George F. Gao, Robert F. Garry, Ian Goodfellow, Stephan Günther, Christian Happi, Edward C Holmes, Brima Kargbo, Paul Kellam, Marion P. G. Koopmans, Nicholas J. Loman, N’Faly Magassouba, Dhamari Naidoo, Stuart T. Nichol, Tolbert Nyenswah, Gustavo Palacios, Oliver G Pybus, Pardis Sabeti, Amadou Sall, Ute Ströher, Isatta Wury, Marc A Suchard, Philippe Lemey, Andrew Rambaut
bioRxiv 071779; doi: https://doi.org/10.1101/071779
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Virus genomes reveal the factors that spread and sustained the West African Ebola epidemic
Gytis Dudas, Luiz Max Carvalho, Trevor Bedford, Andrew J. Tatem, Guy Baele, Nuno Faria, Daniel J. Park, Jason Ladner, Armando Arias, Danny Asogun, Filip Bielejec, Sarah Caddy, Matt Cotten, Jonathan Dambrozio, Simon Dellicour, Antonino Di Caro, Joseph W. Diclaro II, Sophie Duraffour, Mike Elmore, Lawrence Fakoli, Merle Gilbert, Sahr M Gevao, Stephen Gire, Adrianne Gladden-Young, Andreas Gnirke, Augustine Goba, Donald S. Grant, Bart Haagmans, Julian A. Hiscox, Umaru Jah, Brima Kargbo, Jeffrey Kugelman, Di Liu, Jia Lu, Christine M. Malboeuf, Suzanne Mate, David A. Matthews, Christian B. Matranga, Luke Meredith, James Qu, Joshua Quick, Susan D. Pas, My VT Phan, Georgios Poliakis, Chantal Reusken, Mariano Sanchez-Lockhart, Stephen F. Schaffner, John S. Schieffelin, Rachel S. Sealfon, Etienne Simon-Loriere, Saskia L. Smits, Kilian Stoecker, Lucy Thorne, Ekaete A. Tobin, Mohamed A. Vandi, Simon J. Watson, Kendra West, Shannon Whitmer, Michael R. Wiley, Sarah M. Winnicki, Shirlee Wohl, Roman Wölfel, Nathan L. Yozwiak, Kristian G. Andersen, Sylvia Blyden, Fatorma Bolay, Miles Carroll, Boubacar Diallo, Pierre Formenty, Christophe Fraser, George F. Gao, Robert F. Garry, Ian Goodfellow, Stephan Günther, Christian Happi, Edward C Holmes, Brima Kargbo, Paul Kellam, Marion P. G. Koopmans, Nicholas J. Loman, N’Faly Magassouba, Dhamari Naidoo, Stuart T. Nichol, Tolbert Nyenswah, Gustavo Palacios, Oliver G Pybus, Pardis Sabeti, Amadou Sall, Ute Ströher, Isatta Wury, Marc A Suchard, Philippe Lemey, Andrew Rambaut
bioRxiv 071779; doi: https://doi.org/10.1101/071779

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