Advertisement

Meningitis

  • Tone Tønjum
  • Petter Brandtzæg
  • Birgitta Henriques-Normark
Reference work entry

Abstract

Bacterial meningitis is an inflammation of the meninges, including the pia, arachnoid, and subarachnoid space, that occurs in response to infection with bacteria and/or bacterial products. Bacterial meningitis is a significant cause of mortality and morbidity worldwide, with considerable variation in incidence depending on age and geographic location of the patient and the causative agent. Young children are at highest risk for mortality and morbidity, especially those from lower socioeconomic strata in countries with poor medical infrastructure and those infected with Neisseria meningitidis (the meningococcus) or Streptococcus pneumoniae (the pneumococcus). Additional risk factors for poor prognosis after infection include the severity/stage of illness on presentation, exposure to an antibiotic-resistant organism, and the fact that medical professionals lack understanding of mechanisms underlying the pathological features of meningitis. When bacterial meningitis is suspected, immediate action is imperative to establish a definitive diagnosis, and antimicrobial treatment must be initiated immediately as a precautionary measure, because the mortality rate for untreated bacterial meningitis approaches 100 %; even with optimal treatment, mortality and morbidity remain high. Neurological sequelae are relatively common in meningitis survivors, especially if the agent of disease is a pneumococcal microorganism.

Most pathogenic microbes could potentially cause meningitis in the human brain; however, only two pathogens, N. meningitidis and S. pneumoniae, account for most cases of acute bacterial meningitis, when patients in all age groups are considered. In contrast, in very young children and neonates, most cases are caused by group B streptococcus, Escherichia coli, and Listeria monocytogenes. In developing countries, Haemophilus influenza type b and Salmonella species are still major causes of meningitis in infants and young children. Salmonella meningitis has a particularly dismal prognosis. Meningitis is, in the majority of the cases, a consequence of a preceding bacteremia with encapsulated strains. Although the reasons for this association are incompletely understood, bacterial agents that cause meningitis tend to express surface structures mimicking structures and epitopes on human cells and a capsule with antiphagocytic properties that protect them from phagocytosis and normal immune surveillance. Thus, the absence of opsonic or bactericidal antibodies is considered a major risk factor for meningitis. In this regard, age-related incidence of meningococcal and pneumococcal disease is inversely related to prevalence of serum bactericidal activity. Successful identification of microbial epitopes that induce opsonic or bactericidal antibodies and successful vaccination of infants and children using antigenic agents based on these epitopes has changed the epidemiology of bacterial meningitis, particularly due to reduced incidence of Haemophilus influenzae type b-induced meningitis more so in industrialized countries. However, antigenic epitopes suitable for this preventive approach have not been identified in all organisms that cause meningitis with significant frequency today.

Keywords

Bacterial Meningitis Outer Membrane Protein Conjugate Vaccine Invasive Pneumococcal Disease Pneumococcal Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Aas FE, Egge-Jacobsen W, Winther-Larsen HC, Lovold C, Hitchen PG, Dell A, Koomey M (2006) Neisseria gonorrhoeae type IV pili undergo multisite, hierarchical modifications with phosphoethanolamine and phosphocholine requiring an enzyme structurally related to lipopolysaccharide phosphoethanolamine transferases. J Biol Chem 281:27712–27723PubMedCrossRefGoogle Scholar
  2. Achtman M (1995) Epidemic spread and antigenic variability of Neisseria meningitidis. Trends Microbiol 3:186–192PubMedCrossRefGoogle Scholar
  3. Ahmed A, Jafri H, Lutsar I, McCoig CC, Trujillo M, Wubbel L, Shelton S, McCracken GH Jr (1999) Pharmacodynamics of vancomycin for the treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 43:876–881PubMedGoogle Scholar
  4. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511PubMedCrossRefGoogle Scholar
  5. Ambur OH, Davidsen T, Frye SA, Balasingham SV, Lagesen K, Rognes T, Tonjum T (2009) Genome dynamics in major bacterial pathogens. FEMS Microbiol Rev 33:453–470PubMedCrossRefGoogle Scholar
  6. Amiry-Moghaddam M, Frydenlund DS, Ottersen OP (2004) Anchoring of aquaporin-4 in brain: molecular mechanisms and implications for the physiology and pathophysiology of water transport. Neuroscience 129:999–1010PubMedCrossRefGoogle Scholar
  7. Andersen J, Backer V, Voldsgaard P, Skinhoj P, Wandall JH (1997) Acute meningococcal meningitis: analysis of features of the disease according to the age of 255 patients. Copenhagen Meningitis Study Group. J Infect 34:227–235PubMedCrossRefGoogle Scholar
  8. Apicella MA (2005) Neisseria meningitidis. In: Mandell GL, Bennett JE, Dolin R (eds) Principles and practice of infectious diseases. Elsevier/Churchill Livingstone, Philadelphia, pp 2498–2513Google Scholar
  9. Arditi M, Mason EO Jr, Bradley JS, Tan TQ, Barson WJ, Schutze GE, Wald ER, Givner LB, Kim KS, Yogev R, Kaplan SL (1998) Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 102:1087–1097PubMedCrossRefGoogle Scholar
  10. Assalkhou R, Balasingham S, Collins RF, Frye SA, Davidsen T, Benam AV, Bjoras M, Derrick JP, Tonjum T (2007) The outer membrane secretin PilQ from Neisseria meningitidis binds DNA. Microbiology 153:1593–1603PubMedCrossRefGoogle Scholar
  11. Auburtin M, Wolff M, Charpentier J, Varon E, Le Tulzo Y, Girault C, Mohammedi I, Renard B, Mourvillier B, Bruneel F, Ricard JD, Timsit JF (2006) Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study. Crit Care Med 34:2758–2765PubMedCrossRefGoogle Scholar
  12. Baker CJ, Kasper DL (1976) Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N Engl J Med 294:753–756PubMedCrossRefGoogle Scholar
  13. Balasingham SV, Collins RF, Assalkhou R, Homberset H, Frye SA, Derrick JP, Tonjum T (2007) Interactions between the lipoprotein PilP and the secretin PilQ in Neisseria meningitidis. J Bacteriol 189:5716–5727PubMedCrossRefGoogle Scholar
  14. Banerjee A, Van Sorge NM, Sheen TR, Uchiyama S, Mitchell TJ, Doran KS (2010) Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization. Cell Microbiol 12:1576–1588PubMedCrossRefGoogle Scholar
  15. Bergmann S, Hammerschmidt S (2006) Versatility of pneumococcal surface proteins. Microbiology 152:295–303PubMedCrossRefGoogle Scholar
  16. Bermpohl D, Halle A, Freyer D, Dagand E, Braun JS, Bechmann I, Schroder NW, Weber JR (2005) Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways. J Clin Invest 115:1607–1615PubMedCrossRefGoogle Scholar
  17. Biernath KR, Reefhuis J, Whitney CG, Mann EA, Costa P, Eichwald J, Boyle C (2006) Bacterial meningitis among children with cochlear implants beyond 24 months after implantation. Pediatrics 117:284–289PubMedCrossRefGoogle Scholar
  18. Bille E, Zahar JR, Perrin A, Morelle S, Kriz P, Jolley KA, Maiden MC, Dervin C, Nassif X, Tinsley CR (2005) A chromosomally integrated bacteriophage in invasive meningococci. J Exp Med 201:1905–1913PubMedCrossRefGoogle Scholar
  19. Bjune G, Hoiby EA, Gronnesby JK, Arnesen O, Fredriksen JH, Halstensen A, Holten E, Lindbak AK, Nokleby H, Rosenqvist E et al (1991) Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet 338:1093–1096PubMedCrossRefGoogle Scholar
  20. Blomberg C, Dagerhamn J, Dahlberg S, Browall S, Fernebro J, Albiger B, Morfeldt E, Normark S, Henriques-Normark B (2009) Pattern of accessory regions and invasive disease potential in Streptococcus pneumoniae. J Infect Dis 199:1032–1042PubMedCrossRefGoogle Scholar
  21. Boisier P, Nicolas P, Djibo S, Taha MK, Jeanne I, Mainassara HB, Tenebray B, Kairo KK, Giorgini D, Chanteau S (2007) Meningococcal meningitis: unprecedented incidence of serogroup X-related cases in 2006 in Niger. Clin Infect Dis 44:657–663PubMedCrossRefGoogle Scholar
  22. Borchsenius F, Bruun JN, Tonjum T (1991) Systemic meningococcal disease: the diagnosis on admission to hospital. NIPH Ann 14:11–22PubMedGoogle Scholar
  23. Borrow R (2012) Advances with vaccination against Neisseria meningitidis. Trop Med Int Health 1365–3156Google Scholar
  24. Borrow R, Miller E (2006) Long-term protection in children with meningococcal C conjugate vaccination: lessons learned. Expert Rev Vaccines 5:851–857PubMedCrossRefGoogle Scholar
  25. Bourdoulous S, Nassif X (2006) Mechanisms of attachment and invasion. In: Frosch M, Maiden MCJ (eds) Handbook of meningococcal disease. Wiley, Weinheim, pp 257–272CrossRefGoogle Scholar
  26. Bowler LD, Zhang QY, Riou JY, Spratt BG (1994) Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation. J Bacteriol 176:333–337PubMedGoogle Scholar
  27. Brandt CT, Holm D, Liptrot M, Ostergaard C, Lundgren JD, Frimodt-Moller N, Skovsted IC, Rowland IJ (2008) Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis. J Infect Dis 197:235–244PubMedCrossRefGoogle Scholar
  28. Brandtzaeg P (2006) Pathogenesis and pathophysiology of invasive meningococcal disease. In: Frosch M, Maiden MCJ (eds) Handbook of meningococcal disease. Wiley, Weinheim, pp 427–480CrossRefGoogle Scholar
  29. Brandtzaeg P, van Deuren M (2012) Classification and pathogenesis of meningococcal infections. Methods Mol Biol 799:21–35PubMedCrossRefGoogle Scholar
  30. Brigham KS, Sandora TJ (2009) Neisseria meningitidis: epidemiology, treatment and prevention in adolescents. Curr Opin Pediatr 21:437–443PubMedCrossRefGoogle Scholar
  31. Brouwer MC, Tunkel AR, van de Beek D (2010) Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 23:467–492PubMedCrossRefGoogle Scholar
  32. Brueggemann AB, Griffiths DT, Meats E, Peto T, Crook DW, Spratt BG (2003) Clonal relationships between invasive and carriage Streptococcus pneumoniae and serotype- and clone-specific differences in invasive disease potential. J Infect Dis 187:1424–1432PubMedCrossRefGoogle Scholar
  33. Burckhardt I, Burckhardt F, Van Der Linden M, Heeg C, Reinert RR (2010) Risk factor analysis for pneumococcal meningitis in adults with invasive pneumococcal infection. Epidemiol Infect 138:1353–1358PubMedCrossRefGoogle Scholar
  34. Carbonnelle E, Helaine S, Nassif X, Pelicic V (2006) A systematic genetic analysis in Neisseria meningitidis defines the Pil proteins required for assembly, functionality, stabilization and export of type IV pili. Mol Microbiol 61:1510–1522PubMedCrossRefGoogle Scholar
  35. Cartwright K (1995) Introduction and historical aspect. In: Cartwright K (ed) Meningococcal disease. Wiley, Chichester, pp 1–19Google Scholar
  36. Caugant DA, Kristiansen PA, Wang X, Mayer LW, Taha MK, Ouedraogo R, Kandolo D, Bougoudogo F, Sow S, Bonte L (2012) Molecular characterization of invasive meningococcal isolates from countries in the African meningitis belt before introduction of a serogroup A conjugate vaccine. PLoS One 7:e46019PubMedCrossRefGoogle Scholar
  37. Chang CJ, Chang WN, Huang LT, Huang SC, Chang YC, Hung PL, Lu CH, Chang CS, Cheng BC, Lee PY, Wang KW, Chang HW (2004) Bacterial meningitis in infants: the epidemiology, clinical features, and prognostic factors. Brain Dev 26:168–175PubMedCrossRefGoogle Scholar
  38. Chang YC, Uchiyama S, Varki A, Nizet V (2012) Leukocyte inflammatory responses provoked by pneumococcal sialidase. MBio 3:00220–00211CrossRefGoogle Scholar
  39. Chanteau S, Rose AM, Djibo S, Nato F, Boisier P (2007) Biological diagnosis of meningococcal meningitis in the African meningitis belt: current epidemic strategy and new perspectives. Vaccine 25(Suppl 1):A30–A36PubMedCrossRefGoogle Scholar
  40. Chiba N, Murayama SY, Morozumi M, Nakayama E, Okada T, Iwata S, Sunakawa K, Ubukata K (2009) Rapid detection of eight causative pathogens for the diagnosis of bacterial meningitis by real-time PCR. J Infect Chemother 15:92–98PubMedCrossRefGoogle Scholar
  41. Christodoulides M, Makepeace BL, Partridge KA, Kaur D, Fowler MI, Weller RO, Heckels JE (2002) Interaction of Neisseria meningitidis with human meningeal cells induces the secretion of a distinct group of chemotactic, proinflammatory, and growth-factor cytokines. Infect Immun 70:4035–4044PubMedCrossRefGoogle Scholar
  42. Chudwin DS, Wara DW, Lameris-Martin NB, Ammann AJ (1983) Effect of antibody concentration on opsonic requirements for phagocytosis in vitro of Streptococcus pneumoniae types 7 and 19. Proc Soc Exp Biol Med 172:178–186PubMedGoogle Scholar
  43. Clarke TB, Francella N, Huegel A, Weiser JN (2011) Invasive bacterial pathogens exploit TLR-mediated downregulation of tight junction components to facilitate translocation across the epithelium. Cell Host Microbe 9:404–414PubMedCrossRefGoogle Scholar
  44. Claus H, Vogel U, Swiderek H, Frosch M, Schoen C (2007) Microarray analyses of meningococcal genome composition and gene regulation: a review of the recent literature. FEMS Microbiol Rev 31:43–51PubMedCrossRefGoogle Scholar
  45. Collins RF, Frye SA, Kitmitto A, Ford RC, Tonjum T, Derrick JP (2004) Structure of the Neisseria meningitidis outer membrane PilQ secretin complex at 12 A resolution. J Biol Chem 279:39750–39756PubMedCrossRefGoogle Scholar
  46. Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB (2001) Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 39:1553–1558PubMedCrossRefGoogle Scholar
  47. Coureuil M, Join-Lambert O, Lecuyer H, Bourdoulous S, Marullo S, Nassif X (2012) Mechanism of meningeal invasion by Neisseria meningitidis. Virulence 3:164–172PubMedCrossRefGoogle Scholar
  48. Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI (1995) Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377:435–438PubMedCrossRefGoogle Scholar
  49. Darenberg J, Henriques Normark B (2009) The epidemiology of pneumococcal infections—the Swedish experience. Vaccine 27(Suppl 6):G27–G32PubMedCrossRefGoogle Scholar
  50. Davidsen T, Tonjum T (2006) Meningococcal genome dynamics. Nat Rev Microbiol 4:11–22PubMedCrossRefGoogle Scholar
  51. Davidsen T, Koomey M, Tonjum T (2007) Microbial genome dynamics in CNS pathogenesis. Neuroscience 145:1375–1387PubMedCrossRefGoogle Scholar
  52. de Greeff SC, de Melker HE, Schouls LM, Spanjaard L, van Deuren M (2008) Pre-admission clinical course of meningococcal disease and opportunities for the earlier start of appropriate intervention: a prospective epidemiological study on 752 patients in the Netherlands 2003–2005. Eur J Clin Microbiol Infect Dis 27:985–992PubMedCrossRefGoogle Scholar
  53. de Louvois J, Halket S, Harvey D (2005) Neonatal meningitis in England and Wales: sequelae at 5 years of age. Eur J Pediatr 164:730–734PubMedCrossRefGoogle Scholar
  54. Deghmane AE, Alonso JM, Taha MK (2009) Emerging drugs for acute bacterial meningitis. Expert Opin Emerg Drugs 14:381–393PubMedCrossRefGoogle Scholar
  55. Dery MA, Hasbun R (2007) Changing epidemiology of bacterial meningitis. Curr Infect Dis Rep 9:301–307PubMedCrossRefGoogle Scholar
  56. Dillard JP, Hackett KT (2005) Mutations affecting peptidoglycan acetylation in Neisseria gonorrhoeae and Neisseria meningitidis. Infect Immun 73:5697–5705PubMedCrossRefGoogle Scholar
  57. Doulet N, Donnadieu E, Laran-Chich MP, Niedergang F, Nassif X, Couraud PO, Bourdoulous S (2006) Neisseria meningitidis infection of human endothelial cells interferes with leukocyte transmigration by preventing the formation of endothelial docking structures. J Cell Biol 173:627–637PubMedCrossRefGoogle Scholar
  58. Dowson CG, Hutchison A, Brannigan JA, George RC, Hansman D, Linares J, Tomasz A, Smith JM, Spratt BG (1989) Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Proc Natl Acad Sci USA 86:8842–8846PubMedCrossRefGoogle Scholar
  59. Dubos F, De la Rocque F, Levy C, Bingen E, Aujard Y, Cohen R, Breart G, Gendrel D, Chalumeau M (2008) Sensitivity of the bacterial meningitis score in 889 children with bacterial meningitis. J Pediatr 152:378–382PubMedCrossRefGoogle Scholar
  60. Duensing TD, Wing JS, van Putten JP (1999) Sulfated polysaccharide-directed recruitment of mammalian host proteins: a novel strategy in microbial pathogenesis. Infect Immun 67:4463–4468PubMedGoogle Scholar
  61. Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, Rudan I (2010) Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis 10:317–328PubMedCrossRefGoogle Scholar
  62. Emonts M, Hazelzet JA, de Groot R, Hermans PW (2003) Host genetic determinants of Neisseria meningitidis infections. Lancet Infect Dis 3:565–577PubMedCrossRefGoogle Scholar
  63. Faber J, Meyer CU, Gemmer C, Russo A, Finn A, Murdoch C, Zenz W, Mannhalter C, Zabel BU, Schmitt HJ, Habermehl P, Zepp F, Knuf M (2006) Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy. Pediatr Infect Dis J 25:80–81PubMedCrossRefGoogle Scholar
  64. Ferrieri P, Burke B, Nelson J (1980) Production of bacteremia and meningitis in infant rats with group B streptococcal serotypes. Infect Immun 27:1023–1032PubMedGoogle Scholar
  65. Fijen CA, Kuijper EJ, te Bulte MT, Daha MR, Dankert J (1999) Assessment of complement deficiency in patients with meningococcal disease in The Netherlands. Clin Infect Dis 28:98–105PubMedCrossRefGoogle Scholar
  66. Fijen CA, Bredius RG, Kuijper EJ, Out TA, De Haas M, De Wit AP, Daha MR, De Winkel JG (2000) The role of Fcγ receptor polymorphisms and C3 in the immune defence against Neisseria meningitidis in complement-deficient individuals. Clin Exp Immunol 120:338–345PubMedCrossRefGoogle Scholar
  67. Forest KT, Satyshur KA, Worzalla GA, Hansen JK, Herdendorf TJ (2004) The pilus-retraction protein PilT: ultrastructure of the biological assembly. Acta Crystallogr D Biol Crystallogr 60:978–982PubMedCrossRefGoogle Scholar
  68. Fothergill LD, Wright J (1933) Influenzal meningitis: the relation of age incidence to the bactericidal power of blood against the causal organism. J Immunol 24:273–284Google Scholar
  69. Gaggar A, Shayakhmetov DM, Lieber A (2003) CD46 is a cellular receptor for group B adenoviruses. Nat Med 9:1408–1412PubMedCrossRefGoogle Scholar
  70. Galanakis E, Di Cello F, Paul-Satyaseela M, Kim KS (2006) Escherichia coli K1 induces IL-8 expression in human brain microvascular endothelial cells. Eur Cytokine Netw 17:260–265PubMedGoogle Scholar
  71. Gerber J, Redlich S, Ribes S, Tauber SC, Schmidt H, Nau R (2012) Intrathecal treatment with the anti-phosphorylcholine monoclonal antibody TEPC-15 decreases neuronal damage in experimental pneumococcal meningitis. Chemotherapy 58:212–216PubMedCrossRefGoogle Scholar
  72. Giuliani MM, Adu-Bobie J, Comanducci M, Arico B, Savino S, Santini L, Brunelli B, Bambini S, Biolchi A, Capecchi B, Cartocci E, Ciucchi L, Di Marcello F, Ferlicca F, Galli B, Luzzi E, Masignani V, Serruto D, Veggi D, Contorni M, Morandi M, Bartalesi A, Cinotti V, Mannucci D, Titta F, Ovidi E, Welsch JA, Granoff D, Rappuoli R, Pizza M (2006) A universal vaccine for serogroup B meningococcus. Proc Natl Acad Sci USA 103:10834–10839PubMedCrossRefGoogle Scholar
  73. Goldschneider I, Gotschlich EC, Artenstein MS (1969) Human immunity to the meningococcus. II. Development of natural immunity. J Exp Med 129:1327–1348PubMedCrossRefGoogle Scholar
  74. Goonetilleke UR, Scarborough M, Ward SA, Hussain S, Kadioglu A, Gordon SB (2012) Death is associated with complement C3 depletion in cerebrospinal fluid of patients with pneumococcal meningitis. MBio 3:00272–00211CrossRefGoogle Scholar
  75. Gorla MC, de Paiva MV, Salgueiro VC, Lemos AP, Brandao AP, Vazquez JA, Brandileone MC (2011) Antimicrobial susceptibility of Neisseria meningitidis strains isolated from meningitis cases in Brazil from 2006 to 2008. Enferm Infecc Microbiol Clin 29:85–89PubMedCrossRefGoogle Scholar
  76. Gotschlich EC, Goldschneider I, Artenstein MS (1969) Human immunity to the meningococcus. IV. Immunogenicity of group A and group C meningococcal polysaccharides in human volunteers. J Exp Med 129:1367–1384PubMedCrossRefGoogle Scholar
  77. Gray LD, Fedorko DP (1992) Laboratory diagnosis of bacterial meningitis. Clin Microbiol Rev 5:130–145PubMedGoogle Scholar
  78. Gray-Owen SD, Blumberg RS (2006) CEACAM1: contact-dependent control of immunity. Nat Rev Immunol 6:433–446PubMedCrossRefGoogle Scholar
  79. Grijalva CG, Pelton SI (2011) A second-generation pneumococcal conjugate vaccine for prevention of pneumococcal diseases in children. Curr Opin Pediatr 23:98–104PubMedCrossRefGoogle Scholar
  80. Hamilton HL, Dillard JP (2006) Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination. Mol Microbiol 59:376–385PubMedCrossRefGoogle Scholar
  81. Hamilton HL, Dominguez NM, Schwartz KJ, Hackett KT, Dillard JP (2005) Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system. Mol Microbiol 55:1704–1721PubMedCrossRefGoogle Scholar
  82. Hammerschmidt S, Wolff S, Hocke A, Rosseau S, Muller E, Rohde M (2005) Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect Immun 73:4653–4667PubMedCrossRefGoogle Scholar
  83. Harrison OB et al (2002) Analysis of pathogen-host cell interactions in purpura fulminans: expression of capsule, type IV pili, and por A by Neisseria meningitides in vivo. Infect Immun 70:5193–5201PubMedCrossRefGoogle Scholar
  84. Heckenberg SGB, de Gans J, Brouwer MC, Weisfelt M, Piet JR, Spanjarard L, van der Ende A, van de Beek D (2008) Clinical features, outcome, and meningococcal genotype in 258 adults with meningococcal meningitis. Medicine 87:185–192PubMedCrossRefGoogle Scholar
  85. Henrichsen J (1983) Twitching motility. Annu Rev Microbiol 37:81–93PubMedCrossRefGoogle Scholar
  86. Henriques Normark B, Kalin M, Ortqvist A, Akerlund T, Liljequist BO, Hedlund J, Svenson SB, Zhou J, Spratt BG, Normark S, Kallenius G (2001) Dynamics of penicillin-susceptible clones in invasive pneumococcal disease. J Infect Dis 184:861–869PubMedCrossRefGoogle Scholar
  87. Henriques B, Kalin M, Ortqvist A, Olsson Liljequist B, Almela M, Marrie TJ, Mufson MA, Torres A, Woodhead MA, Svenson SB, Kallenius G (2000) Molecular epidemiology of Streptococcus pneumoniae causing invasive disease in 5 countries. J Infect Dis 182:833–839PubMedCrossRefGoogle Scholar
  88. Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M (1999) Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group. Lancet 353:1049–1053PubMedCrossRefGoogle Scholar
  89. Hill DJ, Virji M (2012) Meningococcal ligands and molecular targets of the host. Methods Mol Biol 799:143–152PubMedCrossRefGoogle Scholar
  90. Hiller NL, Janto B, Hogg JS, Boissy R, Yu S, Powell E, Keefe R, Ehrlich NE, Shen K, Hayes J, Barbadora K, Klimke W, Dernovoy D, Tatusova T, Parkhill J, Bentley SD, Post JC, Ehrlich GD, Hu FZ (2007) Comparative genomic analyses of seventeen Streptococcus pneumoniae strains: insights into the pneumococcal supragenome. J Bacteriol 189:8186–8195PubMedCrossRefGoogle Scholar
  91. Hoegen T, Tremel N, Klein M, Angele B, Wagner H, Kirschning C, Pfister HW, Fontana A, Hammerschmidt S, Koedel U (2011) The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-dependent lysosomal cathepsin B release. J Immunol 187:5440–5451PubMedCrossRefGoogle Scholar
  92. Hoffmann I, Eugene E, Nassif X, Couraud PO, Bourdoulous S (2001) Activation of ErbB2 receptor tyrosine kinase supports invasion of endothelial cells by Neisseria meningitidis. J Cell Biol 155:133–143PubMedCrossRefGoogle Scholar
  93. Hoffmann OM, Becker D, Weber JR (2007) Bacterial hydrogen peroxide contributes to cerebral hyperemia during early stages of experimental pneumococcal meningitis. J Cereb Blood Flow Metab 27:1792–1797PubMedCrossRefGoogle Scholar
  94. Hoffmann O, Rung O, Im AR, Freyer D, Zhang J, Held J, Stenzel W, Dame C (2011) Thrombopoietin contributes to neuronal damage in experimental bacterial meningitis. Infect Immun 79:928–936PubMedCrossRefGoogle Scholar
  95. Hsu HE, Shutt KA, Moore MR, Beall BW, Bennett NM, Craig AS, Farley MM, Jorgensen JH, Lexau CA, Petit S, Reingold A, Schaffner W, Thomas A, Whitney CG, Harrison LH (2009) Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med 360:244–256PubMedCrossRefGoogle Scholar
  96. Huang SH, Jong A (2009) Evolving role of laminin receptors in microbial pathogenesis and therapeutics of CNS infection. Future Microbiol 4:959–962PubMedCrossRefGoogle Scholar
  97. Ibarz-Pavon AB, Lemos AP, Gorla MC, Regueira M, Group SW 2nd, Gabastou JM (2012) Laboratory-based surveillance of Neisseria meningitidis isolates from disease cases in Latin American and Caribbean countries, SIREVA II 2006–2010. PLoS One 7:e44102PubMedCrossRefGoogle Scholar
  98. Jit M (2010) The risk of sequelae due to pneumococcal meningitis in high-income countries: a systematic review and meta-analysis. J Infect 61:114–124PubMedCrossRefGoogle Scholar
  99. Johansson L, Rytkonen A, Bergman P, Albiger B, Kallstrom H, Hokfelt T, Agerberth B, Cattaneo R, Jonsson AB (2003) CD46 in meningococcal disease. Science 301:373–375PubMedCrossRefGoogle Scholar
  100. John CC (1994) Treatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: case report and review. Clin Infect Dis 18:188–193PubMedCrossRefGoogle Scholar
  101. Jolley KA, Hill DM, Bratcher HB, Harrison OB, Feavers IM, Parkhill J, Maiden MC (2012) Resolution of a meningococcal disease outbreak from whole-genome sequence data with rapid web-based analysis methods. J Clin Microbiol 50:3046–3053PubMedCrossRefGoogle Scholar
  102. Jyssum K, Lie S (1965) Genetic factors determining competence in transformation of Neisseria Meningitidis. 1. A permanent loss of competence. Acta Pathol Microbiol Scand 63:306–316PubMedGoogle Scholar
  103. Kahler CM, Stephens DS (1998) Genetic basis for biosynthesis, structure, and function of meningococcal lipooligosaccharide (endotoxin). Crit Rev Microbiol 24:281–334PubMedGoogle Scholar
  104. Kahler CM, Datta A, Tzeng YL, Carlson RW, Stephens DS (2005) Inner core assembly and structure of the lipooligosaccharide of Neisseria meningitidis: capacity of strain NMB to express all known immunotype epitopes. Glycobiology 15:409–419PubMedCrossRefGoogle Scholar
  105. Khatami A, Pollard AJ (2011) The epidemiology of meningococcal disease and the impact of vaccines. Expert Rev Vaccines 9:285–298CrossRefGoogle Scholar
  106. Kim KS (2003) Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci 4:376–385PubMedCrossRefGoogle Scholar
  107. Kim KS (2009) Treatment strategies for central nervous system infections. Expert Opin Pharmacother 10:1307–1317PubMedCrossRefGoogle Scholar
  108. Kim KS (2012) Current concepts on the pathogenesis of Escherichia coli meningitis: implications for therapy and prevention. Curr Opin Infect Dis 25:273–278PubMedCrossRefGoogle Scholar
  109. Klugman KP, Friedland IR, Bradley JS (1995) Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis. Antimicrob Agents Chemother 39:1988–1992PubMedCrossRefGoogle Scholar
  110. La Scolea LJ Jr, Dryja D (1984) Quantitation of bacteria in cerebrospinal fluid and blood of children with meningitis and its diagnostic significance. J Clin Microbiol 19:187–190PubMedGoogle Scholar
  111. Lambotin M, Hoffmann I, Laran-Chich MP, Nassif X, Couraud PO, Bourdoulous S (2005) Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a phosphoinositide-3-kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide. J Cell Sci 118:3805–3816PubMedCrossRefGoogle Scholar
  112. Latorre C, Gene A, Juncosa T, Munoz C, Gonzalez-Cuevas A (2000) Neisseria meningitidis: evolution of penicillin resistance and phenotype in a children’s hospital in Barcelona, Spain. Acta Paediatr 89:661–665PubMedCrossRefGoogle Scholar
  113. Leib SL, Heimgartner C, Bifrare YD, Loeffler JM, Taauber MG (2003) Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats. Pediatr Res 54:353–357PubMedCrossRefGoogle Scholar
  114. Levy M, Wong E, Fried D (1990) Diseases that mimic meningitis. Analysis of 650 lumbar punctures. Clin Pediatr (Phila) 29(254–255):258–261Google Scholar
  115. Levy C, Varon E, Bingen E, Lecuyer A, Boucherat M, Cohen R (2011) Pneumococcal meningitis in French children before and after the introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis J 30:168–170PubMedCrossRefGoogle Scholar
  116. Littmann M, Albiger B, Frentzen A, Normark S, Henriques-Normark B, Plant L (2009) Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin expression. EMBO Mol Med 1:211–222PubMedCrossRefGoogle Scholar
  117. Loscher W, Potschka H (2005) Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci 6:591–602. doi:10.1038/nrn1728, nrn1728 [pii]PubMedCrossRefGoogle Scholar
  118. Lu JJ, Perng CL, Lee SY, Wan CC (2000) Use of PCR with universal primers and restriction endonuclease digestions for detection and identification of common bacterial pathogens in cerebrospinal fluid. J Clin Microbiol 38:2076–2080PubMedGoogle Scholar
  119. MacLennan J, Kafatos G, Neal K, Andrews N, Cameron JC, Roberts R, Evans MR, Cann K, Baxter DN, Maiden MC, Stuart JM (2006) Social behavior and meningococcal carriage in British teenagers. Emerg Infect Dis 12:950–957PubMedCrossRefGoogle Scholar
  120. Mahdi LK, Wang H, Van der Hoek MB, Paton JC, Ogunniyi AD (2012) Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice. J Clin Invest 122:2208–2220PubMedCrossRefGoogle Scholar
  121. Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE, Urwin R, Zhang Q, Zhou J, Zurth K, Caugant DA, Feavers IM, Achtman M, Spratt BG (1998) Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci USA 95:3140–3145PubMedCrossRefGoogle Scholar
  122. Major M, Moss S, Gold R (2011) From genes to vaccine: a breakthrough in the prevention of meningococcal group B disease. Paediatr Child Health 16:e61–e64PubMedGoogle Scholar
  123. Manchester M, Eto DS, Valsamakis A, Liton PB, Fernandez-Munoz R, Rota PA, Bellini WJ, Forthal DN, Oldstone MB (2000) Clinical isolates of measles virus use CD46 as a cellular receptor. J Virol 74:3967–3974PubMedCrossRefGoogle Scholar
  124. Marchiafava E, Celli A (1884) Spra i micrococchi della meningite cerebrospinale epidemica. Gazz degli Ospedali 5:59Google Scholar
  125. McGee L (2007) The coming of age of niche vaccines? Effect of vaccines on resistance profiles in Streptococcus pneumoniae. Curr Opin Microbiol 10:473–478PubMedCrossRefGoogle Scholar
  126. Merz AJ, So M (2000) Interactions of pathogenic Neisseriae with epithelial cell membranes. Annu Rev Cell Dev Biol 16:423–457PubMedCrossRefGoogle Scholar
  127. Meyer TF, Pohlner J, van Putten JP (1994) Biology of the pathogenic Neisseriae. Curr Top Microbiol Immunol 192:283–317PubMedCrossRefGoogle Scholar
  128. Miner JR, Heegaard W, Mapes A, Biros M (2001) Presentation, time to antibiotics, and mortality of patients with bacterial meningitis at an urban county medical center. J Emerg Med 21:387–392PubMedCrossRefGoogle Scholar
  129. Molyneux E, Riordan FAI, Walsh A (2006) Acute bacterial meningitis in children presenting to the Royal Liverpool Children’s Hospital, Liverpool, UK and the Queen Elisabeth Central Hospital in Blantyre, Malawi: a world of difference. Ann Trop Paediatr 26:29–37PubMedCrossRefGoogle Scholar
  130. Mustafa MM, Lebel MH, Ramilo O, Olsen KD, Reisch JS, Beutler B, McCracken GH Jr (1989) Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. J Pediatr 115:208–213PubMedCrossRefGoogle Scholar
  131. Nikulin J, Panzner U, Frosch M, Schubert-Unkmeir A (2006) Intracellular survival and replication of Neisseria meningitidis in human brain microvascular endothelial cells. Int J Med Microbiol 296:553–558PubMedCrossRefGoogle Scholar
  132. O’Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N, Lee E, Mulholland K, Levine OS, Cherian T (2009) Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374:893–902PubMedCrossRefGoogle Scholar
  133. Orihuela CJ, Mahdavi J, Thornton J, Mann B, Wooldridge KG, Abouseada N, Oldfield NJ, Self T, Ala’Aldeen DA, Tuomanen EI (2009) Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. J Clin Invest 119:1638–1646PubMedCrossRefGoogle Scholar
  134. Palumbo E, Fiaschi L, Brunelli B, Marchi S, Savino S, Pizza M (2012) Antigen identification starting from the genome: a “Reverse Vaccinology” approach applied to MenB. Methods Mol Biol 799:361–403PubMedCrossRefGoogle Scholar
  135. Parge HE, Forest KT, Hickey MJ, Christensen DA, Getzoff ED, Tainer JA (1995) Structure of the fibre-forming protein pilin at 2.6 A resolution. Nature 378:32–38PubMedCrossRefGoogle Scholar
  136. Parkhill J, Achtman M, James KD, Bentley SD, Churcher C, Klee SR, Morelli G, Basham D, Brown D, Chillingworth T, Davies RM, Davis P, Devlin K, Feltwell T, Hamlin N, Holroyd S, Jagels K, Leather S, Moule S, Mungall K, Quail MA, Rajandream MA, Rutherford KM, Simmonds M, Skelton J, Whitehead S, Spratt BG, Barrell BG (2000) Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 404:502–506. doi:10.1038/35006655PubMedCrossRefGoogle Scholar
  137. Paterson GK, Mitchell TJ (2006) Innate immunity and the pneumococcus. Microbiology 152:285–293PubMedCrossRefGoogle Scholar
  138. Peltola H (2000) Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev 13:302–317PubMedCrossRefGoogle Scholar
  139. Perkins-Balding D, Ratliff-Griffin M, Stojiljkovic I (2004) Iron transport systems in Neisseria meningitidis. Microbiol Mol Biol Rev 68:154–171PubMedCrossRefGoogle Scholar
  140. Plant L, Sundqvist J, Zughaier S, Lovkvist L, Stephens DS, Jonsson AB (2006) Lipooligosaccharide structure contributes to multiple steps in the virulence of Neisseria meningitidis. Infect Immun 74:1360–1367PubMedCrossRefGoogle Scholar
  141. Plummer FA, Chubb H, Simonsen JN, Bosire M, Slaney L, Maclean I, Ndinya-Achola JO, Waiyaki P, Brunham RC (1993) Antibody to Rmp (outer membrane protein 3) increases susceptibility to gonococcal infection. J Clin Invest 91:339–343PubMedCrossRefGoogle Scholar
  142. Power PM, Jennings MP (2003) The genetics of glycosylation in Gram-negative bacteria. FEMS Microbiol Lett 218:211–222PubMedCrossRefGoogle Scholar
  143. Prymula R, Chlibek R, Ivaskeviciene I, Mangarov A, Meszner Z, Perenovska P, Richter D, Salman N, Simurka P, Tamm E, Tesovic G, Urbancikova I, Usonis V (2011) Paediatric pneumococcal disease in Central Europe. Eur J Clin Microbiol Infect Dis 30:1311–1320PubMedCrossRefGoogle Scholar
  144. Quagliarello VJ, Long WJ, Scheld WM (1986) Morphologic alterations of the blood–brain barrier with experimental meningitis in the rat. Temporal sequence and role of encapsulation. J Clin Invest 77:1084–1095PubMedCrossRefGoogle Scholar
  145. Radin JN, Orihuela CJ, Murti G, Guglielmo C, Murray PJ, Tuomanen EI (2005) beta-Arrestin 1 participates in platelet-activating factor receptor-mediated endocytosis of Streptococcus pneumoniae. Infect Immun 73:7827–7835PubMedCrossRefGoogle Scholar
  146. Rappuoli R (2000) Reverse vaccinology. Curr Opin Microbiol 3:445–450PubMedCrossRefGoogle Scholar
  147. Read RC, Pullin J, Gregory S, Borrow R, Kaczmarski EB, di Giovine FS, Dower SK, Cannings C, Wilson AG (2001) A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease. J Infect Dis 184:640–642PubMedCrossRefGoogle Scholar
  148. Reiss A, Braun JS, Jager K, Freyer D, Laube G, Buhrer C, Felderhoff-Muser U, Stadelmann C, Nizet V, Weber JR (2011) Bacterial pore-forming cytolysins induce neuronal damage in a rat model of neonatal meningitis. J Infect Dis 203:393–400PubMedCrossRefGoogle Scholar
  149. Ridda I, Macintyre CR, Lindley R, McIntyre PB, Brown M, Oftadeh S, Sullivan J, Gilbert GL (2010) Lack of pneumococcal carriage in the hospitalised elderly. Vaccine 28:3902–3904PubMedCrossRefGoogle Scholar
  150. Ring A, Weiser JN, Tuomanen EI (1998) Pneumococcal trafficking across the blood–brain barrier. Molecular analysis of a novel bidirectional pathway. J Clin Invest 102:347–360PubMedCrossRefGoogle Scholar
  151. Roberts MC (1989) Plasmids of Neisseria gonorrhoeae and other Neisseria species. Clin Microbiol Rev 2(Suppl):S18–S23PubMedGoogle Scholar
  152. Roine I, Peltola H, Fernandez J, Zavala I, Gonzalez Mata A, Gonzalez Ayala S, Arbo A, Bologna R, Mino G, Goyo J, Lopez E, Dourado de Andrade S, Sarna S (2008) Influence of admission findings on death and neurological outcome from childhood bacterial meningitis. Clin Infect Dis 46:1248–1252PubMedCrossRefGoogle Scholar
  153. Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM (2001) Meningococcal disease. N Engl J Med 344:1378–1388PubMedCrossRefGoogle Scholar
  154. Roy S, Knox K, Segal S, Griffiths D, Moore CE, Welsh KI, Smarason A, Day NP, McPheat WL, Crook DW, Hill AV (2002) MBL genotype and risk of invasive pneumococcal disease: a case–control study. Lancet 359:1569–1573PubMedCrossRefGoogle Scholar
  155. Rubin LL, Staddon JM (1999) The cell biology of the blood–brain barrier. Annu Rev Neurosci 22:11–28PubMedCrossRefGoogle Scholar
  156. Rudel T, Facius D, Barten R, Scheuerpflug I, Nonnenmacher E, Meyer TF (1995) Role of pili and the phase-variable PilC protein in natural competence for transformation of Neisseria gonorrhoeae. Proc Natl Acad Sci USA 92:7986–7990PubMedCrossRefGoogle Scholar
  157. Rupprecht TA, Angele B, Klein M, Heesemann J, Pfister HW, Botto M, Koedel U (2007) Complement C1q and C3 are critical for the innate immune response to Streptococcus pneumoniae in the central nervous system. J Immunol 178:1861–1869PubMedGoogle Scholar
  158. Saha SK, Darmstadt GL, Yamanaka N, Billal DS, Nasreen T, Islam M, Hamer DH (2005) Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden. Pediatr Infect Dis J 24:1093–1098PubMedCrossRefGoogle Scholar
  159. Saha SK, Darmstadt GL, Baqui AH, Hossain B, Islam M, Foster D, Al-Emran H, Naheed A, Arifeen SE, Luby SP, Santosham M, Crook D (2008) Identification of serotype in culture negative pneumococcal meningitis using sequential multiplex PCR: implication for surveillance and vaccine design. PLoS One 3:e3576PubMedCrossRefGoogle Scholar
  160. Sanders MS, van Well GT, Ouburg S, Morre SA, van Furth AM (2011) Genetic variation of innate immune response genes in invasive pneumococcal and meningococcal disease applied to the pathogenesis of meningitis. Genes Immun 12:321–334PubMedCrossRefGoogle Scholar
  161. Sandgren A, Sjostrom K, Olsson-Liljequist B, Christensson B, Samuelsson A, Kronvall G, Henriques Normark B (2004) Effect of clonal and serotype-specific properties on the invasive capacity of Streptococcus pneumoniae. J Infect Dis 189:785–796PubMedCrossRefGoogle Scholar
  162. Sandgren A, Albiger B, Orihuela CJ, Tuomanen E, Normark S, Henriques-Normark B (2005) Virulence in mice of pneumococcal clonal types with known invasive disease potential in humans. J Infect Dis 192:791–800PubMedCrossRefGoogle Scholar
  163. Santoro F, Greenstone HL, Insinga A, Liszewski MK, Atkinson JP, Lusso P, Berger EA (2003) Interaction of glycoprotein H of human herpesvirus 6 with the cellular receptor CD46. J Biol Chem 278:25964–25969PubMedCrossRefGoogle Scholar
  164. Schneider MC, Exley RM, Ram S, Sim RB, Tang CM (2007) Interactions between Neisseria meningitidis and the complement system. Trends Microbiol 15:233–240PubMedCrossRefGoogle Scholar
  165. Schoen C, Blom J, Claus H, Schramm-Gluck A, Brandt P, Muller T, Goesmann A, Joseph B, Konietzny S, Kurzai O, Schmitt C, Friedrich T, Linke B, Vogel U, Frosch M (2008) Whole-genome comparison of disease and carriage strains provides insights into virulence evolution in Neisseria meningitidis. Proc Natl Acad Sci USA 105:3473–3478PubMedCrossRefGoogle Scholar
  166. Schut ES, Lucas MJ, Brouwer MC, Vergouwen MD, van der Ende A, van de Beek D (2012) Cerebral infarction in adults with bacterial meningitis. Neurocrit Care 16:421–427PubMedCrossRefGoogle Scholar
  167. Schuurman T, de Boer RF, Kooistra-Smid AM, van Zwet AA (2004) Prospective study of use of PCR amplification and sequencing of 16S ribosomal DNA from cerebrospinal fluid for diagnosis of bacterial meningitis in a clinical setting. J Clin Microbiol 42:734–740PubMedCrossRefGoogle Scholar
  168. Seki M, Yamashita Y, Torigoe H, Tsuda H, Sato S, Maeno M (2005) Loop-mediated isothermal amplification method targeting the lytA gene for detection of Streptococcus pneumoniae. J Clin Microbiol 43:1581–1586PubMedCrossRefGoogle Scholar
  169. Shanholtzer CJ, Schaper PJ, Peterson LR (1982) Concentrated gram stain smears prepared with a cytospin centrifuge. J Clin Microbiol 16:1052–1056PubMedGoogle Scholar
  170. Sim RJ, Harrison MM, Moxon ER, Tang CM (2000) Underestimation of meningococci in tonsillar tissue by nasopharyngeal swabbing. Lancet 356:1653–1654PubMedCrossRefGoogle Scholar
  171. Sjoholm AG, Braconier JH, Soderstrom C (1982) Properdin deficiency in a family with fulminant meningococcal infections. Clin Exp Immunol 50:291–297PubMedGoogle Scholar
  172. Sjostrom K, Spindler C, Ortqvist A, Kalin M, Sandgren A, Kuhlmann-Berenzon S, Henriques-Normark B (2006) Clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen. Clin Infect Dis 42:451–459PubMedCrossRefGoogle Scholar
  173. Smirnova I, Mann N, Dols A, Derkx HH, Hibberd ML, Levin M, Beutler B (2003) Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility. Proc Natl Acad Sci USA 100:6075–6080PubMedCrossRefGoogle Scholar
  174. Snape MD, Pollard AJ (2005) Meningococcal polysaccharide-protein conjugate vaccines. Lancet Infect Dis 5:21–30PubMedCrossRefGoogle Scholar
  175. Snyder LA, Saunders NJ (2006) The majority of genes in the pathogenic Neisseria species are present in non-pathogenic Neisseria lactamica, including those designated as ‘virulence genes’. BMC Genomics 7:128PubMedCrossRefGoogle Scholar
  176. Snyder LA, Jarvis SA, Saunders NJ (2005) Complete and variant forms of the ‘gonococcal genetic island’ in Neisseria meningitidis. Microbiology 151:4005–4013PubMedCrossRefGoogle Scholar
  177. Sparling PF (1966) Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. J Bacteriol 92:1364–1371PubMedGoogle Scholar
  178. Spratt BG, Zhang QY, Jones DM, Hutchison A, Brannigan JA, Dowson CG (1989) Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis. Proc Natl Acad Sci USA 86:8988–8992PubMedCrossRefGoogle Scholar
  179. Stephens DS (2007) Conquering the meningococcus. FEMS Microbiol Rev 31:3–14PubMedCrossRefGoogle Scholar
  180. Stephens DS, McGee ZA (1981) Attachment of Neisseria meningitidis to human mucosal surfaces: influence of pili and type of receptor cell. J Infect Dis 143:525–532PubMedCrossRefGoogle Scholar
  181. Stephens DS, Hajjeh RA, Baughman WS, Harvey RC, Wenger JD, Farley MM (1995) Sporadic meningococcal disease in adults: results of a 5-year population-based study. Ann Intern Med 123:937–940PubMedGoogle Scholar
  182. Stephens DS, Greenwood B, Brandtzaeg P (2007) Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 369:2196–2210PubMedCrossRefGoogle Scholar
  183. Strom MS, Nunn DN, Lory S (1993) A single bifunctional enzyme, PilD, catalyzes cleavage and N-methylation of proteins belonging to the type IV pilin family. Proc Natl Acad Sci USA 90:2404–2408PubMedCrossRefGoogle Scholar
  184. Swanson J (1973) Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells. J Exp Med 137:571–589PubMedCrossRefGoogle Scholar
  185. Taha MK, Fox A (2007) Quality assessed nonculture techniques for detection and typing of meningococci. FEMS Microbiol Rev 31:37–42PubMedCrossRefGoogle Scholar
  186. Tettelin H, Saunders NJ, Heidelberg J, Jeffries AC, Nelson KE, Eisen JA, Ketchum KA, Hood DW, Peden JF, Dodson RJ, Nelson WC, Gwinn ML, DeBoy R, Peterson JD, Hickey EK, Haft DH, Salzberg SL, White O, Fleischmann RD, Dougherty BA, Mason T, Ciecko A, Parksey DS, Blair E, Cittone H, Clark EB, Cotton MD, Utterback TR, Khouri H, Qin H, Vamathevan J, Gill J, Scarlato V, Masignani V, Pizza M, Grandi G, Sun L, Smith HO, Fraser CM, Moxon ER, Rappuoli R, Venter JC (2000) Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287:1809–1815, 8338 [pii]PubMedCrossRefGoogle Scholar
  187. Thigpen MC, Whitney CG, Messonnier NE, Zell ER, Lynfield R, Hadler JL, Harrison LH, Farley MM, Reingold A, Bennett NM, Craig AS, Schaffner W, Thomas A, Lewis MM, Scallan E, Schuchat A (2011) Bacterial meningitis in the United States, 1998–2007. N Engl J Med 364:2016–2025PubMedCrossRefGoogle Scholar
  188. Tocheva AS, Jefferies JM, Rubery H, Bennett J, Afimeke G, Garland J, Christodoulides M, Faust SN, Clarke SC (2011) Declining serotype coverage of new pneumococcal conjugate vaccines relating to the carriage of Streptococcus pneumoniae in young children. Vaccine 29:4400–4404PubMedCrossRefGoogle Scholar
  189. Tonjum T (2005) Family Neisseriaceae and genus Neisseria. In: Garrity G (ed) Bergey’s manual of systematic bacteriology: the proteobacteria. Springer, New York, pp 775–798Google Scholar
  190. Tonjum T, Koomey M (1997) The pilus colonization factor of pathogenic neisserial species: organelle biogenesis and structure/function relationships—a review. Gene 192:155–163PubMedCrossRefGoogle Scholar
  191. Tonjum T, Caugant DA, Dunham SA, Koomey M (1998) Structure and function of repetitive sequence elements associated with a highly polymorphic domain of the Neisseria meningitidis PilQ protein. Mol Microbiol 29:111–124PubMedCrossRefGoogle Scholar
  192. Tonjum T, Nilsson F, Bruun JN, Haneberg B (1983) The early phase of meningococcal disease. NIPH Ann 6:175–181PubMedGoogle Scholar
  193. Trindade MB, Job V, Contreras-Martel C, Pelicic V, Dessen A (2008) Structure of a widely conserved type IV pilus biogenesis factor that affects the stability of secretin multimers. J Mol Biol 378:1031–1039PubMedCrossRefGoogle Scholar
  194. Tsai CJ, Griffin MR, Nuorti JP, Grijalva CG (2008) Changing epidemiology of pneumococcal meningitis after the introduction of pneumococcal conjugate vaccine in the United States. Clin Infect Dis 46:1664–1672PubMedCrossRefGoogle Scholar
  195. Tsirpouchtsidis A, Hurwitz R, Brinkmann V, Meyer TF, Haas G (2002) Neisserial immunoglobulin A1 protease induces specific T-cell responses in humans. Infect Immun 70:335–344PubMedCrossRefGoogle Scholar
  196. Tully J, Viner RM, Coen PG, Stuart JM, Zambon M, Peckham C, Booth C, Klein N, Kaczmarski E, Booy R (2006) Risk and protective factors for meningococcal disease in adolescents: matched cohort study. BMJ 332:445–450PubMedCrossRefGoogle Scholar
  197. Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ (2004) Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39:1267–1284PubMedCrossRefGoogle Scholar
  198. Turner PC, Southern KW, Spencer NJ, Pullen H (1990) Treatment failure in meningococcal meningitis. Lancet 335:732–733PubMedCrossRefGoogle Scholar
  199. Uchiyama S, Carlin AF, Khosravi A, Weiman S, Banerjee A, Quach D, Hightower G, Mitchell TJ, Doran KS, Nizet V (2009) The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion. J Exp Med 206:1845–1852PubMedCrossRefGoogle Scholar
  200. Unkmeir A, Latsch K, Dietrich G, Wintermeyer E, Schinke B, Schwender S, Kim KS, Eigenthaler M, Frosch M (2002) Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells. Mol Microbiol 46:933–946PubMedCrossRefGoogle Scholar
  201. van de Beek D, Farrar JJ, de Gans J, Mai NT, Molyneux EM, Peltola H, Peto TE, Roine I, Scarborough M, Schultsz C, Thwaites GE, Tuan PQ, Zwinderman AH (2010) Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol 9:254–263PubMedCrossRefGoogle Scholar
  202. van Deuren M, Brandtzaeg P, van der Meer JW (2000) Update on meningococcal disease with emphasis on pathogenesis and clinical management. Clin Microbiol Rev 13:144–166, table of contentsPubMedCrossRefGoogle Scholar
  203. van Ginkel FW, McGhee JR, Watt JM, Campos-Torres A, Parish LA, Briles DE (2003) Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection. Proc Natl Acad Sci USA 100:14363–14367PubMedCrossRefGoogle Scholar
  204. van Hoek AJ, Andrews N, Waight PA, George R, Miller E (2012) Effect of serotype on focus and mortality of invasive pneumococcal disease: coverage of different vaccines and insight into non-vaccine serotypes. PLoS One 7:e39150PubMedCrossRefGoogle Scholar
  205. van Ulsen P, Tommassen J (2006) Protein secretion and secreted proteins in pathogenic Neisseriaceae. FEMS Microbiol Rev 30:292–319PubMedCrossRefGoogle Scholar
  206. van Well GT, Sanders MS, Ouburg S, van Furth AM, Morre SA (2012) Polymorphisms in Toll-like receptors 2, 4, and 9 are highly associated with hearing loss in survivors of bacterial meningitis. PLoS One 7:e35837PubMedCrossRefGoogle Scholar
  207. Vieusseux M (1805) Mémoire su la maladie qui a regné a Genêve au printemps de 1804. J Med Chir Pharmacol 11:163Google Scholar
  208. Vipond C, Mulloy B, Rigsby P, Burkin K, Bolgiano B (2012) Evaluation of a candidate International Standard for Meningococcal Group C polysaccharide. Biologicals 40:353–363PubMedCrossRefGoogle Scholar
  209. Viriyakosol S, Tobias PS, Kitchens RL, Kirkland TN (2001) MD-2 binds to bacterial lipopolysaccharide. J Biol Chem 276:38044–38051PubMedGoogle Scholar
  210. Vogel U, Claus H, Frosch M (2000) Rapid serogroup switching in Neisseria meningitidis. N Engl J Med 342:219–220PubMedCrossRefGoogle Scholar
  211. Weichselbaum A (1887) Ueber die Aetiologie der akuten Meningitis cerebro-spinalis. Fortschr Med 5:573–583Google Scholar
  212. Weisfelt M, van de Beek D, Spanjaard L, Reitsma JB, de Gans J (2006) Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series. Lancet Neurol 5:123–129PubMedCrossRefGoogle Scholar
  213. Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, Reingold A, Cieslak PR, Pilishvili T, Jackson D, Facklam RR, Jorgensen JH, Schuchat A (2003) Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 348:1737–1746PubMedCrossRefGoogle Scholar
  214. WHO (2012) Global alert and responses. http://www.who.int/csr/en
  215. Wippel C, Fortsch C, Hupp S, Maier E, Benz R, Ma J, Mitchell TJ, Iliev AI (2011) Extracellular calcium reduction strongly increases the lytic capacity of pneumolysin from streptococcus pneumoniae in brain tissue. J Infect Dis 204:930–936PubMedCrossRefGoogle Scholar
  216. Wolfgang M, Lauer P, Park HS, Brossay L, Hebert J, Koomey M (1998) PilT mutations lead to simultaneous defects in competence for natural transformation and twitching motility in piliated Neisseria gonorrhoeae. Mol Microbiol 29:321–330PubMedCrossRefGoogle Scholar
  217. Wolfgang M, van Putten JP, Hayes SF, Koomey M (1999) The comP locus of Neisseria gonorrhoeae encodes a type IV prepilin that is dispensable for pilus biogenesis but essential for natural transformation. Mol Microbiol 31:1345–1357PubMedCrossRefGoogle Scholar
  218. Wu YD, Chen LH, Wu XJ, Shang SQ, Lou JT, Du LZ, Zhao ZY (2008) Gram stain-specific-probe-based real-time PCR for diagnosis and discrimination of bacterial neonatal sepsis. J Clin Microbiol 46:2613–2619PubMedCrossRefGoogle Scholar
  219. Yazdankhah SP, Caugant DA (2004) Neisseria meningitidis: an overview of the carriage state. J Med Microbiol 53:821–832PubMedCrossRefGoogle Scholar
  220. Zhang Q, Li Y, Tang CM (2010) The role of the exopolyphosphatase PPX in avoidance by Neisseria meningitidis of complement-mediated killing. J Biol Chem 285(44):34259–34268, PMID 20736171PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Tone Tønjum
    • 1
  • Petter Brandtzæg
    • 2
  • Birgitta Henriques-Normark
    • 3
  1. 1.Centre for Molecular Biology and Neuroscience (CMBN), Department of MicrobiologyUniversity of Oslo, Oslo University HospitalOsloNorway
  2. 2.Department of Pediatrics, Ullevål University HospitalUniversity of OsloOsloNorway
  3. 3.Department of Microbiology, Tumor, and Cell BiologyKarolinska InstitutetStockholmSweden

Personalised recommendations