Molecular epidemiology and mortality of group B streptococcal meningitis and infant sepsis in the Netherlands: a 30-year nationwide surveillance study

Abstract

Streptococcus agalactiae (group B streptococcus) causes invasive disease in all age groups. In the Netherlands, the incidence of group B streptococcal sepsis in early infancy is increasing because of a specific genetic subtype, clonal complex (CC) 17-A1. We assessed the molecular epidemiology, incidence, and mortality of group B streptococcal meningitis in the Netherlands over 30 years. We used nationwide surveillance data from Jan 1, 1987, to Dec 31, 2016, on all group B streptococcal meningitis and sepsis cases. The surveillance database of the Netherlands Reference Laboratory for Bacterial Meningitis-which receives approximately 90% of cerebrospinal fluid isolates from all patients with bacterial meningitis in the Netherlands-was the data source for the study. All patients with group B streptococcus-positive cerebrospinal fluid cultures (meningitis) and infants (0-89 days) with group B streptococcus-positive blood cultures (sepsis) were included. Patients with missing date of birth were excluded. Multi-locus sequence typing and clade profiles were extracted from whole genome sequences. Serotyping was done by latex agglutination and genome sequencing. Survival data was obtained through Municipal Personal Records. 1501 episodes in 1490 patients were identified: 626 meningitis cases (in patients of all ages) and 875 sepsis cases (in patients aged 0-89 days). Mean annual group B streptococcal meningitis incidence was 1·32 per 1 000 000 population. CC17-A1 caused 16 (5%) of 307 meningitis cases in the first half of the study and 77 (26%) of 296 meningitis cases in the second half of the observation period (p<0·0001). Because of a simultaneous decline in CC19, the overall meningitis incidence remained stable. 27 (8%) of 323 patients with meningitis younger than 3 months died and 14 (21%) of 66 patients older than 3 months died. Patients older than 65 years with sequence type (ST) 24 disease were independently associated with death. Serotype III and ST17 were associated with meningitis in early infancy, serotype III remained associated with meningitis in children younger than 3 months after correcting for ST17 (odds ratio 3·71, 95%CI 2·75-5·01). Serotype Ia, Ib, II, III, and V accounted for 98% of the meningitis cases in patients younger than 3 months and 92% cases in patients older than 3 months. CC17-A1 is an increasing cause of group B streptococcal meningitis in all age groups. A pentavalent polysaccharide vaccine would cover most meningitis cases. Netherlands Organization for Health Research and Development and Amsterdam University Medical Centres.