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.
Highlights
Molecular analyses of attachment (G) gene sequences from hospitalized cases suggest that multiple genotypes and variants co-circulate during epidemics and that respiratory syncytial virus (RSV) persistence over successive seasons is characterized by replacement and multiple new introductions of variants
Respiratory syncytial virus (RSV) is a leading viral cause of acute respiratory illnesses (ARI) worldwide (Haynes et al 2013), with the virus infecting 5–10% of the world population annually (Falsey et al 2005) resulting in an estimated 3 million hospitalizations of children aged under 5 years (Nair et al 2010) and more than 160,000 deaths across all age groups each year (Nair et al 2010)
Analysis of RSV strains detected in several parts of the world found that RSV epidemics frequently comprise multiple genotypes but locally a single genotype normally predominates an epidemic with periodic replacement in successive epidemics (Cane et al 1992; Peret et al 1998, 2000; Agoti et al 2015a; Otieno et al 2016)
Summary
Respiratory syncytial virus (RSV) is a leading viral cause of acute respiratory illnesses (ARI) worldwide (Haynes et al 2013), with the virus infecting 5–10% of the world population annually (Falsey et al 2005) resulting in an estimated 3 million hospitalizations of children aged under 5 years (Nair et al 2010) and more than 160,000 deaths across all age groups each year (Nair et al 2010). Information on the origins of RSV seed strains for local epidemics, hubs of virus transmission, and spread patterns during outbreaks is limited (Nokes and Cane 2008; Munywoki et al 2014; Agoti et al 2015a). We pointed out that a large fraction of RSV strains collected from local epidemics possess identical or highly similar G sequences (Agoti et al 2015a; Zlateva et al 2004; 2005) This illustrated the challenge of low phylogenetic resolution in undertaking detailed tracking of RSV transmission in a community by analyzing G gene sequences alone (Munywoki et al 2014). The analysis reported here investigated RSV A transmission in a community setting, the source of seed viruses and genomic diversification in a subset of samples collected during the household cohort study (Munywoki et al 2014). In this report we show the utility of whole genome sequencing in defining RSV transmission, persistence, evolution and spread in households and at the local community level
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