title: Reduced evolutionary rate in reemerged Ebola virus transmission chains.
abstract: On 29 June 2015, Liberia's respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak ("flare-up") of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over.
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Blackley
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wiley
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Jason T
authors.identifier: 0000-0001-7751-4366
authors.initials: JT
authors.lastname: Ladner
authors.affiliation: Ministry of Health, Monrovia, Liberia.
authors.forename: Mosoka
authors.identifier: 0000-0001-8740-4072
authors.initials: M
authors.lastname: Fallah
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: Terrence
authors.initials: T
authors.lastname: Lo
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Merle L
authors.initials: ML
authors.lastname: Gilbert
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gregory
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: D'ambrozio
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: Stewart
authors.identifier: 0000-0003-2963-5440
authors.initials: S
authors.lastname: Coulter
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Mate
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: Zephaniah
authors.initials: Z
authors.lastname: Balogun
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kugelman
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: William
authors.initials: W
authors.lastname: Nwachukwu
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Karla
authors.identifier: 0000-0001-7674-0855
authors.initials: K
authors.lastname: Prieto
authors.affiliation: Ministry of Health, Monrovia, Liberia.
authors.forename: Adolphus
authors.initials: A
authors.lastname: Yeiah
authors.affiliation: Ministry of Health, Monrovia, Liberia.
authors.forename: Fred
authors.initials: F
authors.lastname: Amegashie
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Brian
authors.identifier: 0000-0001-6318-997X
authors.initials: B
authors.lastname: Kearney
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Meagan
authors.initials: M
authors.lastname: Wisniewski
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: John
authors.identifier: 0000-0002-1034-0960
authors.initials: J
authors.lastname: Saindon
authors.affiliation: Illumina Inc., San Diego, CA 92122, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Schroth
authors.affiliation: Liberian Institute for Biomedical Research, Charlesville, Liberia.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fakoli
authors.affiliation: Naval Medical Research Unit No. 3, U.S. Navy, Cairo, Egypt.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Diclaro
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Jens H
authors.identifier: 0000-0002-7800-6045
authors.initials: JH
authors.lastname: Kuhn
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: Ute
authors.initials: U
authors.lastname: Ströher
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: Stuart T
authors.identifier: 0000-0002-7173-5093
authors.initials: ST
authors.lastname: Nichol
authors.affiliation: Ministry of Health, Monrovia, Liberia.
authors.forename: Moses
authors.initials: M
authors.lastname: Massaquoi
authors.affiliation: Ministry of Health, Monrovia, Liberia.
authors.forename: Francis
authors.initials: F
authors.lastname: Kateh
authors.affiliation: World Health Organization, CH-1211 Geneva 27, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Clement
authors.affiliation: World Health Organization, CH-1211 Geneva 27, Switzerland.
authors.forename: Alex
authors.identifier: 0000-0002-1381-2732
authors.initials: A
authors.lastname: Gasasira
authors.affiliation: Liberian Institute for Biomedical Research, Charlesville, Liberia.
authors.forename: Fatorma
authors.initials: F
authors.lastname: Bolay
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: Stephan S
authors.identifier: 0000-0002-5424-716X
authors.initials: SS
authors.lastname: Monroe
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK.; Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.; Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3FL, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Mariano
authors.initials: M
authors.lastname: Sanchez-Lockhart
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: A
authors.initials: A
authors.lastname: Scott Laney
authors.affiliation: Ministry of Health, Monrovia, Liberia.
authors.forename: Tolbert
authors.initials: T
authors.lastname: Nyenswah
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors.forename: Athalia
authors.initials: A
authors.lastname: Christie
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Gustavo
authors.identifier: 0000-0001-5062-1938
authors.initials: G
authors.lastname: Palacios
mesh_terms: D004196:Disease Outbreaks; D029043:Ebolavirus / Q000235:genetics / Q000472:pathogenicity*; D016679:Genome, Viral / Q000235:genetics; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology* / Q000235:genetics / Q000635:transmission* / Q000821:virology; D006801:Humans; D007988:Liberia
keywords: Ebola virus; Ebola virus disease; Liberia; Western Africa; flare-up; persistent infection; reduced evolutionary rate; reemerged; transmission chain