Replication Data for: Defining the vaccination window for respiratory syncytial virus (RSV) using age-seroprevalence data for children in Kilifi, Kenya

Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children To date there are no licensed vaccines for prevention of RSV disease in infants and young children. Some candidate vaccines have shown promising results[6–8]. Most recently, an attenuated vaccine MEDI ΔM2-2, developed by the use of reverse genetics systems has been shown to be highly restricted in replication and more immunogenic in RSV seronegative children than the previous lead live attenuated RSV vaccine candidates [9]. As a result, these findings provide evidence of availability of a promising candidate vaccine for young children and infants in the near future. The primary target for RSV vaccination is children under 6 months of age; a group highly susceptible to severe RSV disease[10]. However, vaccination of this age group is complicated by the presence of maternal antibodies, among other factors[11]. Assuming the efficacy of a potential vaccine is significantly reduced if administered in the presence of maternal antibodies, it follows that the age of vaccination should be delayed. However, a majority of primary RSV infections are acquired early in life[12] and so delaying vaccination could result in missing out on a large proportion of preventable infections. As such a vaccination window or age should be established such that there is minimal maternal antibody interference and a majority of infections have not occurred. In this study we present the age-specific prevalence of antibodies to RSV from a rural community at the Kenyan coast. We then develop three nested catalytic models that explore different assumptions on the RSV specific antibody dynamics. Samples were selected randomly from pediatric admissions to a County hospital in coastal Kenya, and screened for antibodies to RSV by ELISA. The data from this study provides basic understanding on natural response to RSV infection and has a bearing on the optimal age of RSV vaccine delivery.</p

Replication Data for: Transmission patterns and evolution of respiratory syncytial virus in a community outbreak identified by genomic analysis.

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.</p

Specific skills, imperfect information and job rationing

SIGLETIB: RO 2708 (58) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman