Pathogenesis and pathophysiology of bacterial meningitis
- Allan R Tunkel, MD, PhD, MACP
Allan R Tunkel, MD, PhD, MACP
- Professor of Medicine
- Warren Alpert Medical School of Brown University
- Section Editors
- Stephen B Calderwood, MD
Stephen B Calderwood, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine (Microbiology and Immunobiology)
- Harvard Medical School
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
From its original recognition in 1805 until the early 1900s, bacterial meningitis was virtually 100 percent fatal. In 1913, Simon Flexner's introduction of intrathecal meningococcal antiserum prevented some deaths, but the clinical outcome did not dramatically improve until the advent of systemic antimicrobial therapy in the 1930s .
Despite the effectiveness of current antibiotics in clearing bacteria from the cerebrospinal fluid (CSF), bacterial meningitis continues to cause significant morbidity and mortality worldwide. In two large case series, for example, the case-fatality rate for adults with bacterial meningitis was approximately 25 percent, and transient or permanent neurologic morbidity occurred in 21 to 28 percent of survivors [2,3]. (See "Neurologic complications of bacterial meningitis in adults".)
The pathogenesis and pathophysiology of bacterial meningitis involve a complex interplay between virulence factors of the pathogens and the host immune response [4-6]. Much of the damage from this infection is believed to result from cytokines released within the CSF as the host mounts an inflammatory response. (See "Neurologic complications of bacterial meningitis in adults".)
The clinically important issues related to the pathogenesis and pathophysiology of bacterial meningitis will be reviewed here. The clinical features, treatment, prognosis, and prevention of bacterial meningitis in adults and children and issues related to chronic and recurrent meningitis are discussed separately. (See "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Initial therapy and prognosis of bacterial meningitis in adults" and "Treatment of bacterial meningitis caused by specific pathogens in adults" and "Bacterial meningitis in children older than one month: Clinical features and diagnosis" and "Bacterial meningitis in children older than one month: Treatment and prognosis" and "Approach to the patient with chronic meningitis" and "Approach to the adult with recurrent infections", section on 'Meningitis'.)
Bacterial meningitis develops when virulence factors of the pathogen overcome host defense mechanisms. For the most common pathogens causing bacterial meningitis in adults, such as Streptococcus pneumoniae and Neisseria meningitidis, meningeal invasion is related to several virulence factors that allow the bacteria to colonize host mucosal epithelium, invade and survive within the bloodstream, cross the blood-brain barrier, and multiply within the cerebrospinal fluid (CSF). (See "Microbiology and pathobiology of Neisseria meningitidis" and "Epidemiology of Neisseria meningitidis infection".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Schwentker FF, Gelman S, Long PH. Landmark article April 24, 1937. The treatment of meningococcic meningitis with sulfanilamide. Preliminary report. By Francis F. Schwentker, Sidney Gelman, and Perrin H. Long. JAMA 1984; 251:788.
- Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993; 328:21.
- Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med 1998; 129:862.
- Koedel U, Klein M, Pfister HW. New understandings on the pathophysiology of bacterial meningitis. Curr Opin Infect Dis 2010; 23:217.
- Mook-Kanamori BB, Geldhoff M, van der Poll T, van de Beek D. Pathogenesis and pathophysiology of pneumococcal meningitis. Clin Microbiol Rev 2011; 24:557.
- Kim KS. Current concepts on the pathogenesis of Escherichia coli meningitis: implications for therapy and prevention. Curr Opin Infect Dis 2012; 25:273.
- Plaut AG. The IgA1 proteases of pathogenic bacteria. Annu Rev Microbiol 1983; 37:603.
- Stephens DS, Farley MM. Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae. Rev Infect Dis 1991; 13:22.
- Quagliarello V. Dissemination of Neisseria meningitidis. N Engl J Med 2011; 364:1573.
- Joiner KA. Complement evasion by bacteria and parasites. Annu Rev Microbiol 1988; 42:201.
- Brown EJ, Joiner KA, Gaither TA, et al. The interaction of C3b bound to pneumococci with factor H (beta 1H globulin), factor I (C3b/C4b inactivator), and properdin factor B of the human complement system. J Immunol 1983; 131:409.
- Zwijnenburg PJ, van der Poll T, Florquin S, et al. C1 inhibitor treatment improves host defense in pneumococcal meningitis in rats and mice. J Infect Dis 2007; 196:115.
- Brouwer MC, de Gans J, Heckenberg SG, et al. Host genetic susceptibility to pneumococcal and meningococcal disease: a systematic review and meta-analysis. Lancet Infect Dis 2009; 9:31.
- Brouwer MC, Read RC, van de Beek D. Host genetics and outcome in meningococcal disease: a systematic review and meta-analysis. Lancet Infect Dis 2010; 10:262.
- Adriani KS, Brouwer MC, Geldhoff M, et al. Common polymorphisms in the complement system and susceptiblity to bacterial meningitis. J Infect 2013; 66:255.
- Parkkinen J, Korhonen TK, Pere A, et al. Binding sites in the rat brain for Escherichia coli S fimbriae associated with neonatal meningitis. J Clin Invest 1988; 81:860.
- Cundell DR, Gerard C, Idanpaan-Heikkila I, et al. PAf receptor anchors Streptococcus pneumoniae to activated human endothelial cells. Adv Exp Med Biol 1996; 416:89.
- Kim KS. Mechanisms of microbial traversal of the blood-brain barrier. Nat Rev Microbiol 2008; 6:625.
- Simberkoff MS, Moldover NH, Rahal J Jr. Absence of detectable bactericidal and opsonic activities in normal and infected human cerebrospinal fluids. A regional host defense deficiency. J Lab Clin Med 1980; 95:362.
- Tuomanen E, Tomasz A, Hengstler B, Zak O. The relative role of bacterial cell wall and capsule in the induction of inflammation in pneumococcal meningitis. J Infect Dis 1985; 151:535.
- Tuomanen E, Liu H, Hengstler B, et al. The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis 1985; 151:859.
- Wall EC, Gordon SB, Hussain S, et al. Persistence of pneumolysin in the cerebrospinal fluid of patients with pneumococcal meningitis is associated with mortality. Clin Infect Dis 2012; 54:701.
- Wispelwey B, Lesse AJ, Hansen EJ, Scheld WM. Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat. J Clin Invest 1988; 82:1339.
- Moser R, Schleiffenbaum B, Groscurth P, Fehr J. Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest 1989; 83:444.
- Quagliarello VJ, Wispelwey B, Long WJ Jr, Scheld WM. Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. J Clin Invest 1991; 87:1360.
- Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med 1992; 327:864.
- Grandgirard D, Schürch C, Cottagnoud P, Leib SL. Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis. Antimicrob Agents Chemother 2007; 51:2173.
- Quagliarello VJ, Long WJ, Scheld WM. Morphologic alterations of the blood-brain barrier with experimental meningitis in the rat. Temporal sequence and role of encapsulation. J Clin Invest 1986; 77:1084.
- Quagliarello VJ, Ma A, Stukenbrok H, Palade GE. Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat. J Exp Med 1991; 174:657.
- Tureen JH, Dworkin RJ, Kennedy SL, et al. Loss of cerebrovascular autoregulation in experimental meningitis in rabbits. J Clin Invest 1990; 85:577.
- Braun JS, Novak R, Herzog KH, et al. Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat Med 1999; 5:298.
- Kastenbauer S, Koedel U, Becker BF, Pfister HW. Oxidative stress in bacterial meningitis in humans. Neurology 2002; 58:186.
- Nau R, Brück W. Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci 2002; 25:38.