Persistence of Pneumolysin in the Cerebrospinal Fluid of Patients With Pneumococcal Meningitis Is Associated With Mortality

Poor prognosis in Pneumococcal meningitis may be associated with high pneumolysin levels in cerebrospinal fluid (CSF). In patient samples we showed that pneumolysin levels in CSF remained high after 48 hours in nonsurvivors of meningitis compared with survivors. Selective antipneumolysin treatment may present a novel therapeutic option.

Streptococcus pneumoniae accounts for 50% of bacterial meningitis in patients worldwide, carrying a 20% mortality rate in Europe and 50%–60% in sub-Saharan Africa, with up to half of the survivors left with serious neurological sequelae [1, 2]. Streptococcus pneumoniae expresses a range of protein virulence factors associated with colonization of mucosal surfaces and subsequent tissue invasion [3]. Virulence factors include pneumolysin (Ply) and neuraminidase (NanA); Ply is directly associated with neuronal damage [4]. Damage to host tissue is mediated either directly by bacterial proteins or indirectly via the host inflammatory response [5]. Pneumolysin concentrations in cerebrospinal fluid (CSF) in an animal model reach 20 ng/mL−1, a similar concentration to levels found in the CSF of pneumococcal meningitis patients, which were 1–180 ng/mL [4].

Early antibiotic treatment improves the clinical outcome in meningitis [6, 7]. Dexamethasone given as an adjuvant is beneficial in adults with acute pneumococcal meningitis in developed healthcare settings [8] but not in middle- and low-income countries [1]. We tested the hypothesis that persistent pneumococcal protein in CSF might be associated with poor outcome, despite antibiotic therapy.