Differences in survival, brain damage, and cerebrospinal fluid cytokine kinetics due to meningitis caused by 3 different Streptococcus pneumoniae serotypes: evaluation in humans and in 2 experimental models.

Abstract

Experimental meningitis with Streptococcus pneumoniae serotypes 1, 3, and 9 has resulted in pronounced differences in disease severity, but clinical meningitis studies addressing serotype-related differences in case-fatality rates are lacking. Study subjects were Danish patients with pneumococcal meningitis due to serotype 1 (n=38), 3 (n=69), or 9V (n=59) during 1990-2002 for whom clinical information was available. The 3 serotypes were tested for brain damage and cerebrospinal fluid (CSF) inflammatory kinetics in 2 experimental models of meningitis. Patients with serotype 1 had a significantly lower case-fatality rate (3%), compared with patients with serotypes 3 (23%) and 9V (32%) (P=.0047, log-rank test). Age and serotype were independent prognostic factors for fatal outcome. In experimental meningitis, the median number of areas per brain slide with brain damage was significantly lower in rats infected with serotype 1 than in rats infected with serotypes 3 and 9V. Three distinct patterns of brain damage were observed: serotype 1, cortical hemorrhage; serotype 3, cortical necrosis and abscess formation; and serotype 9V, subcortical (callosal) abscess formation. Serotype 1 caused the poorest bacterial growth and lowest CSF levels of white blood cells, tumor necrosis factor- alpha, and interleukin-8 (P<.05). Case-fatality rates of patients with pneumococcal meningitis, the degree and pattern of brain damage, and CSF cytochemical alterations in experimental pneumococcal meningitis differ according to serotype.