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Nationwide prospective study on community-acquired bacterial meningitis: from genetics to therapy

Final Report Summary - MENINGENE (Nationwide prospective study on community-acquired bacterial meningitis: from genetics to therapy)

Bacterial meningitis is a devastating infectious disease of the brain. In a nationwide study we investigated the occurrence and driving genetic factors of host and pathogen of this disease. Introduction of conjugate vaccines has greatly impacted the
epidemiology of bacterial meningitis and nowadays 70% is caused by the pneumococcal bacterium. The death toll is still high despite the introduction of a new therapy, dexamethasone, a strong adjunctive anti-inflammatory treatment. Half of survivors of bacterial meningitis have disabling neurological sequelae. The project has discovered new genetic factors of patient and bacteria indicating a strong interaction between host and bacteria. A well-functioning immune system protects you from getting meningitis, but also providing a risk if the disease occurs. The severity of the inflammatory response determines the outcome, and genetic factors largely determine how active the immune system. Genetic variation in the complement, toll like receptor and interleukin-1 R, and M-TOR-systems play an essential role in meningitis. Bacterial genetic variation determines growth of the bacteria and decreased sensitivity to antibiotics. This project has shown that, in particular, the complement system is of great importance in the outcome of meningitis. Inhibition of the complement system was found in animal experiments to improve the outcome of meningitis.