Group_B_streptococcal_infections_in_neonates__GBS_interaction_with_the_host_innate_immune_system. Group_B_streptococcal_infections_in_neonates__GBS_interaction_with_the_host_innate_immune_system

A progressive increase has been identified in the incidence of GBS neonatal meningitis in the Netherlands between 1987 and 2011, whereas the incidence of E. coli neonatal meningitis has declined over the same 25-year observation period (Bekker et al, 2014. Lancet Infectious Diseases 14:1083-1089). This increase in GBS disease was accompanied by changes in genotype distribution as determined by multi-locus sequence typing (MLST). The introduction of risk-based GBS preventive treatment guidelines in 1999 (consisting of intravenous antibiotic prophylaxis during fever during delivery, premature labour or prolonged rupture of membranes) did not result in the expected decline of GBS disease incidence. We hypothesize that the sensitivity of GBS to the host innate immune response is associated with GBS genotype, and we will will investigate whether: 1. GBS isolates have gained virulence genes over time (whole genome sequencing); and whether 2. GBS strains have accordingly become less vulnerable to the early innate immune responses (cellular test panels, patient-derived GBS strains from our 25-year spanning collection, and virulence gene-specific deletion mutants). Understanding neonatal susceptibility to GBS and a change in bacterial virulence factors will lead to approaches to improve the current prevention strategies. Alternatively, protection by prior multivalent GBS vaccination of pregnant women is being considered a novel strategy to improve immunity in neonates, where success will depend on the correct selection of the vaccine components, which may be used to boost immunity in-vivo. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/.