Bacterial meningitis and the complement system

Bacterial meningitis is a life threatening infectious disease in which bacteria enter the subarachnoid space and meninges surrounding the brain and spinal cord. Mortality ranges between 7-30% in high income countries and half of the survivors develop neuropsychological sequelae.
In the first part of this thesis we describe 1412 episodes of community-acquired bacterial meningitis included in our nationwide prospective cohort study from 2006 to 2014. We observed a decline in incidence from 1.72 cases per 100,000 per year in 2007-2008 to 0.94 per 100,000 per year in 2013-2014. Outcome of pneumococcal meningitis improved substantially compared to our previous cohort with mortality rates declining from 30% to 18%. The proportion of patients treated with adjuvant dexamethasone increased from 17% to 89% and this was independently associated with favourable outcome and increased survival.
The complement system plays a crucial role in the detrimental host inflammatory response during bacterial meningitis. In the second part of this thesis we used translational research to investigate the role of the complement system in bacterial meningitis to find potential targets for new adjuvant treatments. Inhibition of complement component 5 (C5) seems to be the most promising target to improve outcome of pneumococcal meningitis. An alternative approach might be to use anti-C5a antibodies or C5a receptor antagonists, this way the strong anaphylotoxin C5a is inhibited without inhibiting the formation of the membrane attack complex, important in de defence against Neisseria meningitidis. We propose a phase II randomized controlled trial where bacterial meningitis patients are treated with adjuvant IFX-1 (InflaRx).