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Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

Published Online August 28 2014Science 12 September 2014: 
Vol. 345 no. 6202 pp. 1369-1372 
DOI: 10.1126/science.1259657

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Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

1. Stephen K. Gire1,2,*, 
2. Augustine Goba3,*,†, 
3. Kristian G. Andersen1,2,*,†, 
4. Rachel S. G. Sealfon2,4,*, 
5. Daniel J. Park2,*,
6. Lansana Kanneh3, 
7. Simbirie Jalloh3, 
8. Mambu Momoh3,5, 
9. Mohamed Fullah3,5,‡, 
10. Gytis Dudas6, 
11. Shirlee Wohl1,2,7,
12. Lina M. Moses8, 
13. Nathan L. Yozwiak1,2, 
14. Sarah Winnicki1,2, 
15. Christian B. Matranga2, 
16. Christine M. Malboeuf2,
17. James Qu2, 
18. Adrianne D. Gladden2, 
19. Stephen F. Schaffner1,2, 
20. Xiao Yang2, 
21. Pan-Pan Jiang1,2, 
22. Mahan Nekoui1,2,
23. Andres Colubri1, 
24. Moinya Ruth Coomber3, 
25. Mbalu Fonnie3,‡, 
26. Alex Moigboi3,‡, 
27. Michael Gbakie3, 
28. Fatima K. Kamara3,
29. Veronica Tucker3, 
30. Edwin Konuwa3, 
31. Sidiki Saffa3,‡, 
32. Josephine Sellu3, 
33. Abdul Azziz Jalloh3, 
34. Alice Kovoma3,‡,
35. James Koninga3, 
36. Ibrahim Mustapha3, 
37. Kandeh Kargbo3, 
38. Momoh Foday3, 
39. Mohamed Yillah3, 
40. Franklyn Kanneh3,
41. Willie Robert3, 
42. James L. B. Massally3, 
43. Sinéad B. Chapman2, 
44. James Bochicchio2, 
45. Cheryl Murphy2,
46. Chad Nusbaum2, 
47. Sarah Young2, 
48. Bruce W. Birren2, 
49. Donald S. Grant3, 
50. John S. Scheiffelin8, 
51. Eric S. Lander2,7,9,
52. Christian Happi10, 
53. Sahr M. Gevao11, 
54. Andreas Gnirke2,§, 
55. Andrew Rambaut6,12,13,§, 
56. Robert F. Garry8,§,
57. S. Humarr Khan3,‡§, 
58. Pardis C. Sabeti1,2,†§

+Author Affiliations

1. ¹Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
2. ²Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
3. ³Kenema Government Hospital, Kenema, Sierra Leone.
4. ⁴Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5. ⁵Eastern Polytechnic College, Kenema, Sierra Leone.
6. ⁶Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK.
7. ⁷Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
8. ⁸Tulane University Medical Center, New Orleans, LA 70112, USA.
9. ⁹Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
10. ¹⁰Redeemer’s University, Ogun State, Nigeria.
11. ¹¹University of Sierra Leone, Freetown, Sierra Leone.
12. ¹²Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.
13. ¹³Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK.

+Author Notes

• ↵‡ Deceased.

1. ↵†Corresponding author. E-mail: andersen@broadinstitute.org (K.G.A.); augstgoba@yahoo.com (A.G.);psabeti@oeb.harvard.edu (P.C.S.)

1. ↵* These authors contributed equally to this work.

• ABSTRACT
• EDITOR'S SUMMARY

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.

Ebola virus (EBOV; formerly Zaire ebolavirus), one of five ebolaviruses, is a lethal human pathogen, causing Ebola virus disease (EVD) with an average case fatality rate of 78% (1). Previous EVD outbreaks were confined to remote regions of central Africa; the largest, in 1976, had 318 cases (2) (Fig. 1A). The current outbreak started in February 2014 in Guinea, West Africa (3) and spread into Liberia in March, Sierra Leone in May, and Nigeria in late July. It is the largest known EVD outbreak and is expanding exponentially, with a doubling period of 34.8 days (Fig. 1B). As of 19 August 2014, 2240 cases and 1229 deaths have been documented (4, 5). Its emergence in the major cities of Conakry (Guinea), Freetown (Sierra Leone), Monrovia (Liberia), and Lagos (Nigeria) raises the specter of increasing local and international dissemination.

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Fig. 1Ebola outbreaks, historical and current.

(A) Historical EVD outbreaks, colored by decade. Circle area represents total number of cases (RC = Republic of the Congo; DRC = Democratic Republic of Congo). (B) 2014 outbreak growth (confirmed, probable, and suspected cases). (C) Spread of EVD in Sierra Leone by district. The gradient denotes number of cases; the arrow depicts likely direction. (D) EBOV samples from 78 patients were sequenced in two batches, totaling 99 viral genomes [replication = technical replicates (6)]. Mean coverage and median depth of coverage with range are shown. (E) Combined coverage (normalized to the sample average) across sequenced EBOV genomes.