The Netherlands Reference Laboratory for Bacterial Meningitis (NRLBM) had its unofficial start in 1959; Prof. Charlotte Ruys (University of Amsterdam) started collecting and characterizing isolates from patients with meningococcal meningitis across the Netherlands to gain insight into transmission patterns. In 1975, an official collaboration with the National Institute of Public Health and the Environment (RIVM) was initiated and the bacteriological surveillance was expanded to other all-cause community acquired bacterial meningitis.
Currently, the NRLBM yearly receives on average 4,000 bacterial isolates submitted by all Medical Microbiology laboratories nationwide. Submission is on a voluntary basis. These isolates comprise all bacterial isolates (~300 per year) cultured from cerebrospinal fluid (CSF) as well as culture negative PCR-positive CSF samples from patients with bacterial meningitis (~60 per year). Remaining isolates are predominantly from blood or other normally sterile bodily sites from patients with other invasive bacterial disease presentations. All received bacterial isolates characterized by serogrouping/serotyping and/or subtyped, as relevant for that particular species, to provide insight into the incidence and molecular epidemiology of invasive bacterial infections in the Netherlands. All isolates are stored. Since its initiation, the NRLBM has archived ~110,000 isolates (up to Oct 2025) and these strains are available for studies on the epidemiology of bacterial meningitis, invasive disease and on the pathogenicity and antibiotic susceptibility of isolates.
Objectives of the NRLBM
perform surveillance of community-acquired bacterial meningitis and other invasive bacterial infections;
perform diagnosis with molecular methods in culture-negative patient specimens
describe the (molecular) epidemiology of community-acquired bacterial meningitis and select invasive bacterial infections in the Netherlands;
provide insights and performs research on potential new vaccine components;
provide insight into type-specific antibiotic susceptibility of isolates.
Surveillance task
S. pneumoniae, N. meningitidis and H. influenzae, the three main causes of bacterial meningitis, have been the historical focus of the NRLBM with regard to national bacteriological surveillance. Vaccines against these three pathogens are now included in the National Immunization Program and infections with these pathogens are notifiable for specific age groups. The NRLBM shares the bacteriological information of the submitted isolates for these three pathogens with the National Institute of Public Health and Environment (RIVM), where the information is linked to the information from the mandatory notifications to closely monitor vaccine efficacy or possible changes in epidemiology or outbreaks. The NRLBM performs the following typing for these three pathogens:
- S. pneumoniae: serogrouping and sero(sub)typing using co-agglutination and Quellung assays; penicillin and oxacillin resistance. In the absence of an isolate, DNA is isolated and used for qPCR analysis targeting the pia and lytR genes, whole genome sequencing in case of outbreaks or noticeable changes in epidemiology.
- N. meningitidis: serogrouping through Ouchterlony, phenotypic penicillin and rifampicine resistance, porA and fetA genosubtyping. In the absence of an isolate, DNA is isolated and used for qPCR analysis targeting the soda gene and serogroup-specific genes.
- H. influenzae: serotyping using co-agglutination, b-lactamase production, biotyping for non-typeable H. influenzae isolates. In the absence of an isolate, DNA is isolated and used for qPCR analysis targeting the siaT gene.
Over the years, the NRLBM has expanded national surveillance to invasive diseases (including meningitis) caused by other bacterial species such as the neonatal pathogens Escherichia coli and Streptococcus agalactiae (Group B Streptococcus), and for all ages Streptococcus pyogenes (Group A Streptococcus; all manifestations notifiable since January 2023) and Listeria monocytogenes (notifiable). For Listeria infections, the also NRLBM collaborates with the RIVM with regard to yearly reporting and identification of clusters and source tracing.