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Transmission patterns and evolution of respiratory syncytial virus in a community outbreak identified by genomic analysis

Title: Transmission patterns and evolution of respiratory syncytial virus in a community outbreak identified by genomic analysis
Authors: Agoti, CN
Munywoki, PK
Phan, MVT
Otieno, JR
Kamau, E
Bett, A
Kombe, I
Githinji, G
Medley, GF
Cane, PA
Kellam, P
Cotten, M
Nokes, DJ
Item Type: Journal Article
Abstract: Detailed information on the source, spread and evolution of respiratory syncytial virus (RSV) during seasonal community outbreaks remains sparse. Molecular analyses of attachment (G) gene sequences from hospitalized cases suggest that multiple genotypes and variants co-circulate during epidemics and that RSV persistence over successive seasons is characterized by replacement and multiple new introductions of variants. No studies have defined the patterns of introduction, spread and evolution of RSV at the local community and household level. We present a whole genome sequence analysis of 131 RSV group A viruses collected during 6-month household-based RSV infection surveillance in Coastal Kenya, 2010 within an area of 12 km2. RSV infections were identified by regular symptom-independent screening of all household members twice weekly. Phylogenetic analysis revealed that the RSV A viruses in nine households were closely related to genotype GA2 and fell within a single branch of the global phylogeny. Genomic analysis allowed the detection of household-specific variation in seven households. For comparison, using only G gene analysis, household-specific variation was found only in one of the nine households. Nucleotide changes were observed both intra-host (viruses identified from same individual in follow-up sampling) and inter-host (viruses identified from different household members) and these coupled with sampling dates enabled a partial reconstruction of the within household transmission chains. The genomic evolutionary rate for the household dataset was estimated as 2.307 × 10 − 3 (95% highest posterior density: 0.935–4.165× 10 − 3) substitutions/site/year. We conclude that (i) at the household level, most RSV infections arise from the introduction of a single virus variant followed by accumulation of household specific variation and (ii) analysis of complete virus genomes is crucial to better understand viral transmission in the community. A key question arising is whether prevention of RSV introduction or spread within the household by vaccinating key transmitting household members would lead to a reduced onward community-wide transmission.
Issue Date: 11-Mar-2017
Date of Acceptance: 1-Mar-2017
URI: http://hdl.handle.net/10044/1/61786
DOI: https://dx.doi.org/10.1093/ve/vex006
ISSN: 2057-1577
Publisher: Oxford University Press
Journal / Book Title: VIRUS EVOLUTION
Volume: 3
Issue: 1
Copyright Statement: © 2017 The Author. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
full-genome sequencing
RSV
WAIFW
household transmission
community transmission
MAXIMUM-LIKELIHOOD PHYLOGENIES
CIRCULATION PATTERNS
SUBGROUP-A
MOLECULAR EVOLUTION
GENETIC-VARIABILITY
HOUSEHOLD COHORT
VIRAL-INFECTIONS
KILIFI DISTRICT
G-GLYCOPROTEIN
ATTACHMENT-G
Publication Status: Published
Article Number: vex006
Online Publication Date: 2017-03-11
Appears in Collections:Department of Medicine
Faculty of Medicine



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