Invasive group B streptococcal disease in the Netherlands

In the first part of this thesis, we provided an overview of the epidemiology of bacterial meningitis over the past three decades in the Netherlands and described the impact of conjugate vaccines against Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae. In the second part of this thesis, we focussed on GBS as a causative pathogen of bacterial meningitis in all age-groups and sepsis and meningitis in neonates and young infants. We addressed several aspects, including the incidence, acute mortality and long-term disability in survivors to estimate the current burden of disease and to calculate cost-effectiveness of future vaccines. We described the clinical characteristics of adults with GBS meningitis, and found that GBS meningitis mainly occurs in adults with underlying conditions such as immunocompromised state, cerebrospinal fluid leakage, and endocarditis. We subsequently described the molecular epidemiology of GBS isolates that caused bacterial meningitis the Netherlands over the past 30 years. We observed a steady increase of neonatal GBS disease due to the emergence of a hypervirulent genetic GBS subtype. Furthermore, we described higher mortality rates in children with invasive GBS disease and observed a higher risk of long-term neurodevelopmental impairment in survivors compared to children without a history of GBS disease. Strategies to prevent invasive disease in infants have not resulted in declining incidence rates in the Netherlands. Maternal immunization is a promising new strategy to prevent neonatal GBS disease. A pentavalent polysaccharide conjugate vaccine against GBS holds the potential to prevent most of the invasive GBS disease cases in young infants in the Netherlands.