Bacterial meningitis is a life-threatening infection of the brain in which a complex interplay the bacteria and the host inflammatory response determines the outcome. Genetic studies have provided important clues to which mechanisms play a role in the response to the bacteria and secondary damage to the brain. Blocking such mechanisms is now studied to improve the prognosis in patient with bacterial meningitis.

Ongoing data collection

Bacterial meningitis is a severe infection of the membranes surrounding the brain in which both the bacteria and the patient’s immune response contribute to damage of the brain. Despite treatment with antibiotics and anti-inflammatory therapy (dexamethasone), still one in five patients dies and half of the survivors have neurological sequelae.

The neuro-infections research group of Amsterdam UMC has an ongoing nationwide prospective cohort study since 2006 in which currently over 2500 patients have been included. From these patients we collect clinical data, DNA, blood and cerebrospinal fluid samples, and DNA. Furthermore, we collect the bacteria isolated from the cerebrospinal fluid and analyse the bacterial DNA as well. Finally, in patients who died from bacterial meningitis we study the brain to get a detailed analysis of the disease process.

Translational research

By combining the information from the patient and bacteria we aim to dissect the harmful interaction between host and pathogen in bacterial meningitis leading to brain damage and eventually death. Blocking these harmful mechanisms is thought to reduce the disease severity and improve outcome.

In a translational research design, we start with the patients’ materials to perform genetic analysis, extensive measurements of gene expression and protein levels, and brain pathology analysis. In a next step, we perform experimental studies to validate these findings in an experimental setting using cell lines experiments and a zebra fish embryo model. In these models we can study the effect of new treatments, which we subsequently test in patients in a randomized clinical trial.

Some of the researchers involved