Genetics and outcome of bacterial meningitis

Bacterial meningitis is a severe disease with a high morbidity and mortality. The last decennia adjunctive treatment with dexamethasone is added to the standard treatment with antibiotics and has changed the course of disease. The first part of this thesis describes the epidemiology, clinical characteristics and outcome of bacterial meningitis in this new era with adjunctive dexamethasone treatment. In a cross sectional cohort study, long term sequelae of pneumococcal meningitis were evaluated 1 to 5 years after acute illness. Neurological sequelae were often present and patients performed worse on neuropsychological tests compared to controls. Besides patients experienced a lower quality of life and had more often sleeping disturbances.
It is no fully understood why some people develop meningitis and others do not, or why some people survive the acute illness and others do not. Probably an interaction between environmental-, virulence- and susceptibility factors of the host (like a compromised immune system or genetics) play a role in this. The second part of this thesis aims to gain more insight in these factors influencing susceptibility and outcome of disease. This is done by investigating the inflammatory response of bacterial meningitis patients and how this is related to outcome of disease. Besides, two genetic associations studies are performed, one comparing the frequency of genetic variants between patients and controls and one between patients in different outcome groups. Finally an overview is given, presented as a systemic review, with all genetic association studies on susceptibility, phenotype and outcome of (invasive) pneumococcal disease.