Bacterial meningitis: epidemiology, herd protection, clinical characteristics, and risk assessment

This thesis studied the epidemiology of community-acquired bacterial meningitis after the nationwide implementation of paediatric conjugate vaccines, as well as the long-term epidemiology of invasive meningococcal disease and neonatal group B streptococcal disease in the Netherlands. Furthermore, clinical features of adult community-acquired bacterial meningitis after the introduction of adjunctive dexamethasone therapy and routine paediatric conjugate vaccines were investigated in a prospective nationwide cohort. Predictors of severe illness were found, both in adults with bacterial meningitis as well as in patients presenting with cerebrospinal pleocytosis and a negative cerebrospinal fluid gram stain. A risk score was developed that identifies adults with cerebrospinal fluid pleocytosis and a negative cerebrospinal fluid Gram stain at low risk of an urgent treatable cause, and an external validation study of nine risk scores that predict adverse clinical outcome in bacterial meningitis was performed. Risk scores were identified through a systematic review of the literature. We found that bacterial meningitis is still a formidable disease with high mortality and morbidity, but progress has been made over the last decades. Outcome has been improved substantially by the introduction of adjunctive dexamethasone. Conjugate paediatric vaccines have greatly reduced the incidence of meningococcal, pneumococcal and H. influenzae type b meningitis. These vaccines have been unexpectedly effective against colonization and transmission, thereby making it possible to protect infants, immunocompromised patients, and the elderly by vaccinating healthy carriers. High quality and long-term surveillance studies will remain essential for vaccine development, implementation and evaluation.