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Nature. 2016 Feb 11;530(7589):228-232. doi: 10.1038/nature16996. Epub 2016 Feb 3.

Real-time, portable genome sequencing for Ebola surveillance.

Author information

1
Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.
2
The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
3
Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
4
Ontario Institute for Cancer Research, Toronto, Canada.
5
Department of Computer Science, University of Toronto, Toronto, Canada.
6
European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
7
National Infection Service, Public Health England, London, UK.
8
Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK.
9
Postgraduate Training for Applied Epidemiology (PAE, German FETP), Robert Koch Institute, Berlin, Germany.
10
Public Health England, Porton Down, Wiltshire SP4 0JG, UK.
11
Swiss Tropical and Public Health Institute, Basel, Switzerland.
12
Robert Koch Institute, Berlin, Germany.
13
University College London, London, UK.
14
Paul-Ehrlich-Institut, Division of Veterinary Medicine, Langen, Germany.
15
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
16
Laboratory for Clinical and Epidemiological Virology, Department of Microbiology and Immunology, KU Leuven, Belgium.
17
Ministry of Health Guinea, Conakry, Guinea.
18
Kenya Medical Research Institute, Nairobi, Kenya.
19
National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
20
Friedrich-Loeffler-Institute, Greifswald, Germany.
21
Spiez Laboratory, Spiez, Switzerland.
22
Janssen-Cilag, Stockholm, Sweden.
23
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, L69 7BE.
24
Institute of Virology, Technische Universität München, Munich, Germany.
25
Public Health Agency of Canada, Winnipeg, Canada.
26
Institut Pasteur Dakar, Dakar, Senegal.
27
Laboratoire de Fièvres Hémorragiques de Guinée, Conakry, Guinea.
28
Sandia National Laboratories, Albuquerque, New Mexico, USA.
29
Ratoma Ebola Diagnostic Center, Conakry, Guinea.
30
MRIGlobal, Kansas City, USA.
31
Expertise France, Laboratoire K-plan de Forecariah en Guinée, Paris, France.
32
Fédération des Laboratoires - HIA Bégin, Paris, France.
33
Laboratoire de Biologie - Centre de Traitement des Soignants, Conakry, Guinée.
34
World Health Organization, Conakry, Guinea.
35
London School of Hygiene and Tropical Medicine, London, UK.
36
Norwegian Institute of Public Health, Oslo, Norway.
37
Public Health Wales, Cardiff, UK.
38
Defence Science and Technology Laboratory (Dstl) Porton Down, Salisbury SP4 0JQ, UK.
39
Oxford Nanopore Technologies, Oxford, UK.
40
Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
41
Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham, UK.
42
Centre of Defence Pathology, Royal Centre of Defence Medicine, Birmingham UK.
43
Queen Elizabeth Hospital, Birmingham, UK.
44
Bundeswehr Institute of Microbiology, Munich, Germany.
45
Institut National de Santé Publique, Conakry, Guinea.
46
Fogarty International Center, National Institutes of Health, Bethesda, USA.
47
Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 2FL, UK.
48
University of Southampton, South General Hospital, Southampton SO16 6YD, UK.
49
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, PHE Porton Down, UK.
#
Contributed equally

Abstract

The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10(-3) and 1.42 × 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.

PMID:
26840485
PMCID:
PMC4817224
DOI:
10.1038/nature16996
[Indexed for MEDLINE]
Free PMC Article

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