Project Details

Early Career

Status: Funded - Open

Whole-genome sequencing of group B Streptococcus to establish pathogen genetic associations with transmission

Kirsty Le Doare, MD, PhD, MRCPCH

Summary

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis in many countries and although early-onset GBS disease is thought to be associated with transmission of an infecting strain between mother and child, we know little about transmission dynamics in late-onset disease. Whole genome sequencing has enabled the identification of certain strains that are more likely to cause invasive disease.

GAP: It is not known whether transmission of bacteria from mother to infant occurs after birth or whether the infant gut harbors pathogens that cause episodes of late onset sepsis.

HYPOTHESIS:

1. Bacterial genetic identifiers can be used to determine GBS transmission from colonised mothers to neonates.

2. Specific GBS genetic variants are associated with the ability to colonise the infant intestine

METHODS: 750 mother-infant pair samples collected in a Thrasher Foundation funded study in The Gambia in 2014. Will be analysed including: maternal rectovaginal swabs and breastmilk; infant rectal and nasopharyngeal swabs at birth, 6-7 and 60-89 days. Whole-genome sequencing of GBS isolates will be used to determine phylogeny, sequence types and identify factors associated with transmission and persistent colonisation.

RESULTS: Pending.

IMPACT: Understanding transmission and pathogen genetics for GBS could inform targeted intervention strategies such as decolonization of colonized mothers and newborns to reduce the risk of infant infection. Alternatively, it may be possible to design an intervention to specifically prevent establishment of chorioamnionitis, which could have advantages over intravenous penicillin in preventing the initiation of sepsis in labour. Finally, this work could inform selection of protein vaccine targets for GBS and establish the validity of infant colonisation as an endpoint for vaccine efficacy.