Uncovering infant group B streptococcal (GBS) disease clusters in the UK and Ireland through genomic analysis: a population-based epidemiological study
Background: The true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases. Methods: Potentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7-89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists. Results: Analysis of sequences indicated a cut-off of =5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically-identical pairs with 0 SNP differences, one pair with 3 SNP differences, one cluster of 4 cases with =1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and one an early-onset index case. Serial intervals between cases ranged from 0-59 (median 12) days. Conclusions: Approximately one in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of clusters were previously undetected, emphasising the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation.