The fundamental steps in the pathophysiology of meningitis

Streptococcus pneumoniae is the most frequent cause of acute bacterial meningitis with a case fatality rate of 17 - 30%. Majority of patients that survive suffer from neurological sequelae such a cognitive impairment, behaviour problems, seizures or paralysis. The pathophysiology of pneumococcal meningitis remains to be elucidated however, the host immune response and the interactions between the pathogen and immune cells appears to play a crucial role in disease outcome. Animal models has greatly improved scientific knowledge in understanding diseases and appropriate treatment options however, many lack translatability resulting in failed human clinical trials despite promising results in animal experimentation. This project will exploit a new experimental infection model to assess disease progression and test both pathogen and host-directed therapeutic interventions. The long-term aim is to improve translatability to humans resulting in better prioritisation of drugs entering clinical tail and translating into better treatment outcomes.