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Bacterial meningitis: Mechanisms of disease and therapy

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Abstract

Bacterial meningitis continues to be a serious infectious disease with a high morbidity and mortality in young children. Early recognition and initiation of adequate treatment are the major determinants for a good outcome. Recent advances in our understanding of the host inflammatory response by cytokines may result in the use of new therapeutic strategies. Such modulation of the inflammatory response may reduce the incidence of sequelae and death. The use of steroids as adjunctive therapy in children with bacterial meningitis probably has beneficial effects although the available data are still controversial. Additionally, studies in experimental meningitis models indicate that non-steroidal anti-inflammatory drugs and monoclonal antibodies against bacterial products, cytokines and CD18 on leucocytes reduce the extent of the meningeal inflammation. Human studies to evaluate the efficacy of these immune modulators are expected to start soon. However, prevention of bacterial meningitis by conjugate vaccines againstStreptococcus pneumoniae andNeisseria meningitidis will be the most promising development in the next decade.

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Abbreviations

ADH :

antidiuretic hormone

BBB :

blood brain barrierHib Haemophilus influenzae type b

IFN :

interferon

IL :

interleukin

LPS :

lipopolysaccharide

PAF :

platelet activating factor

PGE 2 :

prostaglandin E2

PMN :

polymorphonuclear leucocyte

SIADH :

syndrome of inappropriate secretion of antidiuretic hormone

TNF :

tumour necrosis factor

References

  1. Alexander HE (1943) Treatment of Haemophilus influenzae infections and of meningococcic and pneumococcic meningitis. Am J Dis Child 66: 172–187

    Google Scholar 

  2. American Academy of Pediatrics (1991) Report of the Committee on infectious diseases, 22nd edn. Am Acad Pediatr, Elk Groove Village, pp 324, 375, 566–577

    Google Scholar 

  3. Arditi M, Ables L, Yogev R (1989) Cerebrospinal fluid endotoxin levels in children withH. influenzae meningitis before and after administration of intravenous ceftriaxone. J Infect Dis 160: 1005–1011

    PubMed  Google Scholar 

  4. Arditi M, Manogue KR, Caplan M, Yogev R (1990) Cerebrospinal fluid cachectin/tumor necrosis factor-α and platelet-activating factor concentrations and severity of bacterial meningitis in children. J Infect Dis 162: 139–147

    PubMed  Google Scholar 

  5. Baggiolini M, Walz A, Kunkel SL (1989) Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 84: 1045–1049

    PubMed  Google Scholar 

  6. Baraff LJ, Lee SI, Schriger DL (1993) Outcomes of bacterial meningitis in children: a meta-analysis. Pediatr Infect Dis J 12: 389–394

    PubMed  Google Scholar 

  7. Baumgartner J-D, Allen McCutchan J, Melle G van, Vogt M, Luethy R, Glauser MP, Ziegler EJ, Klauber MR, Muehlen E, Chiolero R, Geroulanos S (1985) Prevention of gram-negative shock and death in surgical patients by antibody to endotoxin core glycolipid. Lancet: 59–63

  8. Betz SJ, Henson PM (1980) Production and release of platelet-activating factor (PAF); dissociation from degranulation and superoxide production in the human neutrophil. J Immunol 125: 2756–2763

    PubMed  Google Scholar 

  9. Beutler B, Krochin N, Milsark IW, Luedke C, Cerami A (1986) Control of cachectin (tumor necrosis factor) synthesis: mechanism of endotoxin resistance. Science 232: 977–980

    PubMed  Google Scholar 

  10. Bjune G, Hoiby EA, Gronnesby JK, Arnesen O, Fredriksen JH, Halstensen A, Holten E, Lindbak A-K, Nokleby H, Rosenqvist E, Solberg LK, Closs O, Eng J, Froholm LO, Lystad A, Bakketeig LS, Hareide B (1991) Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet: 1093–1096

  11. Burroughs M, Cabellos C, Prasad S, Tuomanen E (1992) Bacterial components and the pathophysiology of injury to the blood-brain barrier: does cell wall add to the effects of endotoxin in gram-negative meningitis? J Infect Dis 165: S82–85

    Google Scholar 

  12. Cabellos C, Macintyre DE, Forrest M, Burroughs M, Prasad S, Tuomanen E (1992) Differing roles for platelet-activating factor during inflammation of the lung and subarachnoid space. J Clin Invest 90: 612–618

    PubMed  Google Scholar 

  13. Campos J, García-Tornel S, Sanfeliu I (1984) Susceptibility studies of multiply resistantHaemophilus influenzae isolated from pediatric patients and contacts. Antimicrob Agents Chemother 25: 706–709

    PubMed  Google Scholar 

  14. Campos J, García-Tornel S (1987) Comparative susceptibilities of ampicillin and chloramphenicol resistantHaemophilus influenzae to fifteen antibiotics. J Antimicrob Chemother 19: 297–301

    PubMed  Google Scholar 

  15. Cassio de Moraes J, Perkins BA, Camargo MCC, Rossetto Hidalgo NT, Aparecida Barbosa H, Tavares Sacchi C, Land Gral IM, Gattas VL, G Vasconcelos H de, Plikaytis BD, Wenger JD, Broome CV (1992) Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil. Lancet 340: 1074–1078

    Article  PubMed  Google Scholar 

  16. Chan PH, Fishman RA (1979) Brain edema: induction in cortical slices by polyunsaturated fatty acids. Science 201: 358–360

    Google Scholar 

  17. Chao CC, Hu S, Close K, Choi CS, Molitor TW, Novick WJ, Peterson PK (1992) Cytokine release from microglia: differential inhibition by pentoxifylline and dexamethasone. J Infect Dis 166: 847–853

    PubMed  Google Scholar 

  18. Chavanet P, Bonnotte B, Guiguet M, Zeller V, Solary E, Maurice L, Casasnovas O, Caillot D, Waldner A, Kisterman JP, Portier H (1992) High concentrations of intrathecal interleukin-6 in human bacterial and nonbacterial meningitis. J Infect Dis 166: 428–431

    PubMed  Google Scholar 

  19. Cherubin CE, Eng RHK, Norrby R, Modai J, Humbert G, Overturf G (1989) Penetration of newer cephalosporins into cerespinal fluid. Rev Infect Dis 11: 526–548

    PubMed  Google Scholar 

  20. Clemens JD, Ferreccio C, Levine MM, Horwitz I, Rao MR, Eng M, Edwards KM, Fritzell B (1992) Impact ofHaemophilus influenzae type b polysaccaride-tetanus protein conjugate vaccine on responses to concurrently administered diphtheria-tetanuspertussis vaccine. JAMA 267: 673–678

    Article  PubMed  Google Scholar 

  21. Cooper A, Beaty H, Oppenheimer S, Goodner R, Petersdorf R (1968) Studies on the pathogenesis of meningitis. Glucose transport and spinal fluid production in experimental pneumococcal meningitis. J Lab Clin Med 71: 473–483

    PubMed  Google Scholar 

  22. Eskola J, Peltola H, Takala AK, Käyhty H, Hakulinen M, Karanko V, Kela E, Rekola P, Rönnberg PR, Samuelson JS, Gordon LK, Mäkelä PH (1987) Efficacy ofHaemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in infancy. N Engl J Med 317: 717–722

    PubMed  Google Scholar 

  23. Eskola J, Käyhty H, Takala AK, Peltola H, Rönnberg P-R, Kela E, Pekkanen E, McVerry PH, Mäkelä PH (1990) A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasiveHaemophilus influenzae type b disease. N Engl J Med 323: 1381–1387

    PubMed  Google Scholar 

  24. Farley MM, Stephens DS, Mulks MH (1986) Pathogenesis of IgA1 protease-producing and-nonproducingHaemophilus influenzae in human nasopharyngeal organ cultures. J Infect Dis 154: 752–759

    PubMed  Google Scholar 

  25. Feigin RD (1987) Bacterial meningitis beyond the newborn period. In: Feigin RD, Cherry JD (eds) Textbook of pediatric infectious diseases. Saunders, Philadelphia, pp 439–465

    Google Scholar 

  26. Feldman RA, Koehler RE, Fraser DW (1976) Race-specific differences in bacterial meningitis deaths in the United States, 1962–1968. Am J Publ Health 66: 392–396

    Google Scholar 

  27. Finland M, Brown JW, Rauh AE (1938) Treatment of pneumococcic meningitis. A study of 10 cases treated with sulfanilamide alone or in various combinations with specific antipneumococci serum and complement, including six recoveries. N Engl J Med 218: 1033–1044

    Google Scholar 

  28. Fishman RA, Sligar K, Hake RB (1977) Effects of leukocytes on brain metabolism in granulocytic brain edema. Ann Neurol 2: 89–94

    Article  Google Scholar 

  29. Flexner S (1906) Experimental cerebrospinal meningitis and its serum treatment. JAMA 47: 560–566

    Google Scholar 

  30. Flexner S (1913) The result of serum treatment in 1300 cases of epidemic meningitis. J Exp Med 17: 553–576

    Article  Google Scholar 

  31. Floyd RF, Federspiel CF, Schaffner W (1974) Bacterial meningitis in urban and rural Tennessee. Am J Epidemiol 99: 395–407

    PubMed  Google Scholar 

  32. Fong IW, Tomkins KB (1984) Penetration of ceftazidime into the cerebrospinal fluid of patients with and without evidence of meningeal inflammation. Antimicrob Agents Chemother 26: 115–116

    PubMed  Google Scholar 

  33. Fortnum HM (1992) Hearing impairment after bacterial meningitis: a review. Arch Dis Child 67: 1128–1133

    PubMed  Google Scholar 

  34. Frasch CE (1989) Vaccines for prevention of meningoccocal disease. Clin Microbiol Rev 2: S134–138

    Google Scholar 

  35. Fraser DW, Geil CC, Feldman RA (1974) Bacterial meningitis in Bernalillo County, New Mexico: a comparison with three other American populations. Am J Epidemiol 100: 29–34

    PubMed  Google Scholar 

  36. Garvey RJP, McMullin GP (1983) Meningitis due to β-lactamase producing type bHaemophilus influenzae resistant to chloramphenicol. BMJ 287: 1183–1184

    Google Scholar 

  37. Gigliotti F, Lee D, Insel RA, Scheld WM (1987) IgG penetration into the cerebrospinal fluid in a rabbit model of meningitis. J Infect Dis 156: 394–398

    PubMed  Google Scholar 

  38. Girgis NI, Farid Z, Mikhail IA, Farrag I, Sultan Y, Kilpatrick ME (1989) Dexamethasone treatment for bacterial meningitis in children and adults. Pediatr Infect Dis J 8: 848–851

    PubMed  Google Scholar 

  39. Glimåker M, Kragsbjerg P, Forsgren M, Olcén P (1993) Tumor necrosis factor-α (TNFα) in cerebrospinal fluid from patients with meningitis of different etiologies: high levels of TNFα indicate bacterial meningitis. J Infect Dis 167: 882–889

    PubMed  Google Scholar 

  40. Granoff DM, Cates KL (1985)Haemophilus influenzae type b polysaccharide vaccines. J Pediatr 107: 330–336

    PubMed  Google Scholar 

  41. Granoff DM, Anderson EL, Osterholm MT, Holmes SJ, McHugh JE, Belshe RB, Medley F, Murphy TV (1992) Differences in the immunogenicity of threeHaemophilus influenzae type b conjugate vaccines in infants. J Pediatr 121: 187–194

    PubMed  Google Scholar 

  42. Groot de R, Dzoljic-Danilovic G, Klingerden van B, Goessens WHF, Neijens HJ (1991) Antibiotic resistance inHaemophilus influenzae: mechanisms, clinical importance and consequences for therapy. Eur J Pediatr 150: 534–546

    Article  PubMed  Google Scholar 

  43. Guerra-Romero L, Täuber MG, Fournier MA, Tureen JH (1992) Lactate and glucose concentrations in brain interstitial fluid, cerebrospinal fluid, and serum during experimental pneumococcal meningitis. J Infect Dis 166: 546–550

    PubMed  Google Scholar 

  44. Hatch D, Overturf GD, Kovacs A, Forthal D, Leong C (1986) Treatment of bacterial meningitis with ceftazidime. Pediatr Infect Dis J 5: 416–420

    Google Scholar 

  45. Hoffman SL, Rustama D, Punjabi NH, et al (1988) High-dose dexamethasone in quinine-treated patients with cerebral malaria: a double-blind, placebo-controlled trial. J Infect Dis 158: 325–331

    PubMed  Google Scholar 

  46. Hughes BJ, Hollers JC, Crockett-Torabi E, Smith CW (1992) Recruitment of CD11b/CD18 to the neutrophil surface and adherence-dependent cell locomotion. J Clin Invest 90: 1687–1696

    PubMed  Google Scholar 

  47. Infectious Disease and Immunization Committee, Canadian Paediatric Society (1990) Dexamethasone therapy for bacterial meningitis: a time for caution. Can Med Assoc J 142:307–308

    Google Scholar 

  48. Ingraham JL, Maaloe O, Neidhardt FC (1983) Growth of the bacterial cell. Sinauer Associates 3, Sunderland, MA

    Google Scholar 

  49. Kadurugamuwa JL, Hengstler B, Zak O (1987) Effects of antiinflammatory drugs on arachidonic acid metabolites and cerebrospinal fluid proteins during infectious pneumococcal meningitis in rabbits. Pediatr Infect Dis J 6: 1153–1154

    Google Scholar 

  50. Kadurugamuwa JL, Hengstler B, Bray MA, Zak O (1989) Inhibition of complement-factor-5a-induced inflammatory reactions by prostaglandin E2 in experimental meningitis. J Infect Dis 160: 715–719

    PubMed  Google Scholar 

  51. Kadurugamuwa JL, Hengstler B, Zak O (1989) Cerebrospinal fluid protein profile in experimental pneumococcal meningitis and its alteration by ampicillin and antiinflammatory agents. J Infect Dis 159: 26–34

    PubMed  Google Scholar 

  52. Kaplan SL, Feigin RD (1978) The syndrome of inappropriate secretion of antidiuretic hormone in children with bacterial meningitis. J Pediatr 92: 758–761

    PubMed  Google Scholar 

  53. Käyhty H, Eskola J, Peltola H, Rönnberg P-R, Kela E, Karanko V, Saarinen L (1991) Antibody responses to fourHaemophilus influenzae type b conjugate vaccines. JAMA 145: 223–227

    Google Scholar 

  54. Kern JA, Lamb RJ, Reed JC, Daniele RP, Nowell PC (1988) Dexamethasone inhibition of interleukin-1β production by human monocytes. J Clin Invest 81: 237–244

    PubMed  Google Scholar 

  55. King SM, Law B, Langley J, Heurter H, Bremner D, Wang E, Gold R (1992) A randomized controlled trial of dexamethasone versus placebo in children with bacterial meningitis (abstract 72). Program and abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Am Soc Microbiol, Washington, p 122

  56. Klein NJ, Heyderman RS, Levin M (1992) Antibiotic choices for meningitis beyond the neonatal period. Arch Dis Child 67: 157–161

    PubMed  Google Scholar 

  57. Lebel MH, Freij BJ, Syrogiannopoulos GA, Chrane DF, Jean Hoyt M, Stewart SM, Kennard BD, Olsen KD, McCracken GH (1988) Dexamethason therapy for bacterial meningitis. Result of two double-blind, placebocontrolled trials. N Engl J Med 319: 964–971

    PubMed  Google Scholar 

  58. Lee SW, Tsou AP, Chan H (1988) Glucocorticoids selectively inhibit the transcription of the interleukin-1β gene and decrease the stability of interleukin-1β mRNA. Proc Natl Acad Sci USA 85: 1204–1208

    PubMed  Google Scholar 

  59. Leist TP, Frei K, Kam-Hansen S, Zinkernagel RM, Fontana A (1988) Tumor necrosis factor α in cerebrospinal fluid during bacterial, but not viral, meningitis. J Exp Med 167: 1743–1748

    Article  PubMed  Google Scholar 

  60. Ley van der P, Biezen van der J, Hohenstein P, Peeters C, Poolman JT (1993). Use of transformation to construct antigenic hybrids of the class 1 outer membrane protein inNeisseria meningitidis. Infect Immun 61: 4217–4224

    PubMed  Google Scholar 

  61. López-Cortés LF, Cruz-Ruiz M, Gómez-Mateos J, Jiménez-Hernádez D, Palomino J, Jiménez E (1993) Measurement of levels of tumor necrosis factor-α and interleukin-1β in the CSF of patients with meningitis of different etiologies: utility in the differential diagnosis. Clin Infect Dis 16: 534–539

    PubMed  Google Scholar 

  62. Lynn WA, Raetz CRH, Qureshi N, Golenbock DT (1991) Lipopolysaccharide-induced stimulation of CD11/CD18 expression on neutrophils. Evidence of specific receptorbased response and inhibition by lipid A-based antagonists. J Immunol 147: 3072–3079

    PubMed  Google Scholar 

  63. Machka K, Braveny I, Dabernat H, Dornbusch K, Dyck E van, Kayser FH, Klingeren B van, Mittermayer H, Perea E, Powell M (1988) Distribution and resistance patterns ofHaemophilus influenzae: a European cooperative study. Eur J Clin Microbiol Infect Dis 7: 14–24

    Article  PubMed  Google Scholar 

  64. Marcus AJ (1988) Eicosanoids: transcellular metabolism. In: Gallin JJ, Goldstein JM, Snyderman R (eds) Inflammation: basic principles and clinical correlates. Raven Press, New York, pp 129–138

    Google Scholar 

  65. McCracken GH, Mize SG, Threlkeld N (1980) Intraventricular gentamicin therapy in gram-negative bacillary meningitis of infancy. Report of the second neonatal meningitis cooperative study group. Lancet: 787–791

  66. McCracken GH, Mustafa MM, Ramilo O, Olsen KD, Risser RC (1989) Cerebrospinal fluid interleukin 1-beta and tumor necrosis factor concentration and outcome from neonatal gram-negative enteric bacillary meningitis. Pediatr Infect Dis J 8: 155–159

    PubMed  Google Scholar 

  67. Møller B, Mogensen SC, Wendelboe P, Bendtzen K, Petersen CM (1991) Bioactive and inactive forms of tumor necrosis factor-α in spinal fluid from patients with meningitis. J Infect Dis 163: 886–889

    PubMed  Google Scholar 

  68. Moser R, Schleiffenbaum B, Groscurth P, Fehr J (1989) Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest 83: 444–455

    PubMed  Google Scholar 

  69. Mustafa MM, Lebel MH, Ramilo O, Olsen KD, Reisch JS, Beutler B, McCracken GH (1989) Correlation of interleukin-1β and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. J Pediatr 115: 208–213

    PubMed  Google Scholar 

  70. Mustafa MM, Mertsola J, Ramilo O, Sáez-Llorens X, Risser RC, McCracken GH (1989) Increased endotoxin and interleukin-1β concentrations in cerebrospinal fluid of infants with coliform meningitis and ventriculitis associated with intraventricular gentamicin therapy. J Infect Dis 160: 891–895

    PubMed  Google Scholar 

  71. Mustafa MM, Ramilo O, Mertsola J, Risser RC, Beutler B, Hansen EJ, McCracken GH (1989) Modulation of inflammation and cachectin activity in relation to treatment of experimentalHemophilus influenzae type b meningitis. J Infect Dis 160: 818–825

    PubMed  Google Scholar 

  72. Mustafa MM, Ramilo O, Olsen KD, Franklin PS, Hansen EJ, Beutler B, McCracken GH (1989) Tumor necrosis factor in mediating experimentalHaemophilus influezae type b meningitis. J Clin Invest 84: 1253–1259

    PubMed  Google Scholar 

  73. Mustafa MM, Ramilo O, Sáez-Llorens X, Olsen KD, Magness RR, McCracken GH (1990) Cerebrospinal fluid prostaglandins, interleukin 1β, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethason-treated patients. Am J Dis Child 144: 883–887

    PubMed  Google Scholar 

  74. Naworth PP, Stern DM (1986) Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 163: 740–745

    Article  PubMed  Google Scholar 

  75. Neu HC (1987) Cephalosporins in the treatment of meningitis. Drugs 34 [Suppl]: 135–153

    PubMed  Google Scholar 

  76. Odio CM, Faingezicht I, Paris M, Nassar M, Baltodano A, Rogers J, Sáez-Llorens X, Olsen KD, McCracken GH (1991) The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med 324: 1525–1531

    PubMed  Google Scholar 

  77. Ohga S, Aoki T, Okada K, Akeda H, Fujioka K, Ohshima A, Mori T, Minamishima, Ueda K (1994) Cerebrospinal fluid concentrations of interleukin-1β, tumor necrosis factor-α, and interferon gamma in bacterial meningitis. Arch Dis Child 70: 123–125

    PubMed  Google Scholar 

  78. Peltola H, Käyhty H, Virtanen M, Mäkelä PH (1984) Prevention ofHemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med 310: 1561–1566

    PubMed  Google Scholar 

  79. Peltola H, Kilpi T, Anttila M (1992) Rapid disappearance ofHaemophilus influenzae type b meningitis after routine childhood immunisation with conjugate vaccines. Lancet 340: 592–594

    Article  PubMed  Google Scholar 

  80. Pfister HW, Koedel U, Haberl RL, Dirnagl U, Feiden W, Ruckdeschel G, Einhäupl KM (1990) Microvascular changes during the early phase of experimental bacterial meningitis. J Cereb Blood Flow Metab 10:914–922

    PubMed  Google Scholar 

  81. Pfister HW, Ködel U, Dirnagl, Haberl RL, Ruckdeschel G, Einhäupl KM (1992) Effect of catalase on regional cerebral blood flow and brain edema during the early phase of experimental pneumococcal meningitis. J Infect Dis 166: 1442–1445

    PubMed  Google Scholar 

  82. Pinckard RN, Ludwig JC, McManus LM (1988) Platelet-activating factors. In: Gallin JJ, Goldstein JM, Snyderman R (eds) Inflammation: basic principles and clinical correlates. Raven Press, New York, pp 139–168

    Google Scholar 

  83. Plaut AG (1983) The IGA1 proteases of pathogenic bacteria. Annu Rev Microbiol 37: 603–622

    Article  PubMed  Google Scholar 

  84. Pober JS, Cotran RS (1990) Cytokines and endothelial cell biology. Physiol Rev 70: 427–451

    PubMed  Google Scholar 

  85. Pober JS, LaPierre LA, Stolpen AH, Brock TA, Springer TA, Fiers W, Bevilacqua MP, Mendrick DL, Gimbrone MA (1987) Activation of cultured endothelial cells by recombinant lymphotoxin: comparison with tumor necrosis factor and interleukin-1 species. J Immunol 138: 3319–3324

    PubMed  Google Scholar 

  86. Pomeroy SL, Holmes SJ, Dodge PR, Feigin RD (1990) Seizures and other neurologic sequelae of bacterial meningitis in children. N Engl J Med 323: 1651–1657

    PubMed  Google Scholar 

  87. Powell KR, Sugerman LI, Eskenazi AE, Woodlin KA, Kays MA, McCormick KL, Miller ME, Sladek CD (1990) Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy. J Pediatr 117: 515–522

    PubMed  Google Scholar 

  88. Prockop L, Fishman R (1966) Pathophysiology of the cerebrospinal fluid changes in experimental pneumococcal meningitis. Trans Am Neurol Assoc 91: 126–131

    Google Scholar 

  89. Radetsky M (1990) Duration of treatment in bacterial meningitis: a historical inquiry. Pediatr Infect Dis J 9: 2–9

    PubMed  Google Scholar 

  90. Ramilo O, Mustafa MM, Porter J, Sáez-Llorens X, Mertsola J, Olsen KD, Luby JP, Beutler B, McCracken GH (1990) Detection of interleukin 1β but not tumor necrosis factor-α in cerebrospinal fluid in children with aseptic meningitis. Am J Dis Child 144: 349–352

    PubMed  Google Scholar 

  91. Ramilo O, Sáez-Llorens X, Mertsola J, et al (1990) Tumor necrosis factor α/cachectin and interleukin-1β initiate meningeal inflammation. J Exp Med 172: 497–507

    Article  PubMed  Google Scholar 

  92. Rodriguez WJ, Puig JR, Khan WN, Feris J, Gold BG, Sturla C (1986) Ceftazidime vs. standard therapy for pediatric meningitis: therapeutic, pharmacologic and epidemiologic observations. Pediatr Infect Dis 5: 408–415

    PubMed  Google Scholar 

  93. Rothlein R, Czaikowski M, O'Neil MM, Martin D, Mainolfi E, Merluzzi J (1988) Induction of intercellular adhesion molecule-1 on primary and continuous cell lines by pro-inflammatory cytokines. J Immunol 141: 1665–1669

    PubMed  Google Scholar 

  94. Sáez-Llorens X, Ramilo O, Mustafa MM, Mertsola J, Alba C de, Hansen E, McCracken GH (1990) Pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis. Antimicrob Agents Chemother 34: 837–843

    PubMed  Google Scholar 

  95. Sáez-Llorens X, Jafari HS, Severien C, Parras F, Olsen KD, Hansen EJ, Singer II, McCracken GH (1991) Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimentalHaemophilus meningitis. J Clin Invest 88: 2003–2011

    PubMed  Google Scholar 

  96. Sáez-Nieto JA, Lujan R, Berrón, Campos J, Viñas M, Fusté C, Vazquez JA, Zhang QY, Bowler LD, Martinez-Suarez JV, Spratt BG (1992) Epidemiology and molecular basis of penicillin-resistentNeisseria meningitidis in Spain: a 5-year history (1985–1989) Clin Infect Dis 14: 394–402

    PubMed  Google Scholar 

  97. Sapolsky RM, Pulsinelli WA (1985) Glucocorticoids potentiate ischemic injury to neurons: therapeutic implications. Science 1985; 229: 1397–1400

    Google Scholar 

  98. Schaad UB, Lips U, Gnehm HE, Blumberg A, Heinzer I, Wedgwood J, for the Swiss Meningitis Study Group (1993) Dexamethasone therapy for bacterial meningitis in children. Lancet 342: 457–461

    Article  PubMed  Google Scholar 

  99. Scheld WM (1987) Morphofunctional alterations of the blood-brain barrier during experimental meningitis. Pediatr Infect Dis J 6: 1145–1146

    Google Scholar 

  100. Scheld WM, Dacey RC, Winn HR, Welsh JE, Jane JA, Sande MA (1980) Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis: alterations with penicillin and methylprednisolone. J Clin Invest 66: 243–253

    PubMed  Google Scholar 

  101. Sell SH (1983) Long term sequelae of bacterial meningitis in children. Pediatr Inf Dis 2: 90–93

    Google Scholar 

  102. Simasathien S, Duangmani C, Echeverria P (1980)Haemophilus influenzae type b resistant to ampicillin and chloramphenicol in an orphanage in Thailand. Lancet II: 1214–1217

    Article  Google Scholar 

  103. Springer TA (1990) Adhesion receptors of the immune system. Nature 346: 425–434

    Article  PubMed  Google Scholar 

  104. Steele RW (1989) Cephalosporins for bacterial meningitis: which one is best?. J Pediatr 114: 991–992

    PubMed  Google Scholar 

  105. Steinhoff MC, Edwards K, Keyserling H, Thoms ML, Johnson C, Madore D, Hogerman D (1994) A randomized comparison of three bivalentStreptococcus pneumoniae glycoprotein conjugate vaccines in young children: effect of polysaccharide size and linkage characteristics. Pediatr Infect Dis J 13: 368–372

    PubMed  Google Scholar 

  106. Stephens DS, Farley MM (1991) Pathogenic events during infection of the human nasopharynx withNeisseria meningitidis andHaemophilus influenzae. Rev Infect Dis 13: 22–33

    PubMed  Google Scholar 

  107. Stephens DS, Hoffman LH, McGee ZA (1983) Interaction ofNeisseria meningitidis with human nasopharyngeal mucosa: attachment and entry into columnar epithelial cells. J Infect Dis 148: 369–376

    PubMed  Google Scholar 

  108. Sullivan GW, Carper HT, Novick WJ, Mandell GL (1988) Inhibition of inflammatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxifylline. Infect Immun 57: 1722–1729

    Google Scholar 

  109. Syrogiannopoulos GA, Olsen KD, Reisch JS, McCracken GH (1987) Dexamethasone in the treatment of experimentalHaemophilus influenzae type b meningitis. J Infect Dis 155: 213–219

    PubMed  Google Scholar 

  110. Syrogiannopoulos GA, Hansen EJ, Erwin AL, Munford RS, Rutledge J, Reisch JS, McCracken GH (1988)Haemophilus influenzae type b lipooligosaccharide induces meningeal inflammation. J Infect Dis 157: 237–244

    PubMed  Google Scholar 

  111. Täuber MG, Khayam-Bashi H, Sande MA (1985) Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis. J Infect Dis 151: 528–534

    PubMed  Google Scholar 

  112. Täuber MG, Shibi AM, Hackbarth CJ, Larrick JW, Sande MA (1987) Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimentalEscherichia coli meningitis in rabbits. J Infect Dis 156: 528–534

    Google Scholar 

  113. Täuber MG, Borschberg U, Sande SA (1988) Influence of granulocytes on brain edema, intracranial pressure, and cerebrospinal fluid concentrations of lactate and protein in experimental meningitis. J Infect Dis 157: 456–464

    PubMed  Google Scholar 

  114. Täuber MG, Sande E, Fournier MA, Tureen JH, Sande MA (1993) Fluid administration, brain edema, and cerebrospinal fluid lactate and glucose concentrations in experimentalEscherichia coli meningitis. J Infect Dis 168: 473–476

    PubMed  Google Scholar 

  115. Taylor HG, Michaels RH, Mazur PM, Bauer RE, Liden CB (1984) Intellectual, neuropsychological, and achievement outcomes in children six to eight years after recovery fromHaemophilus influenzae meningitis. Pediatrics 74: 198–205

    PubMed  Google Scholar 

  116. Taylor HG, Mills EL, Ciampi A, Berger R du, Watters GV, Gold R, MacDonald N, Michaels RH (1990) The sequelae ofHaemophilus influenzae meningitis in school-age children. N Engl J Med 323: 1657–1663

    PubMed  Google Scholar 

  117. Tuomanen E, Tomasz A, Hengstler B, Zak O (1985) The relative role of bacterial cell wall and capsule in the induction of inflammation in pneumococcal meningitis. J Infect Dis 151: 535–540

    PubMed  Google Scholar 

  118. Tuomanen E, Liu H, Hengstler B, Zak O, Tomasz A (1985) The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis 151: 858–868

    Google Scholar 

  119. Tuomanen E, Hengstler B, Rich R, Bray MA, Zak O, Tomasz A (1987) Nonsteroidal anti-inflammatory agents in the therapy for experimental pneumococcal meningitis. J Infect Dis 155: 985–990

    PubMed  Google Scholar 

  120. Tuomanen EI, Saukkonen K, Sande S, Cioffe C, Wright SD (1989) Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesionpromoting receptors of leukocytes. J Exp Med 170: 959–968

    Article  PubMed  Google Scholar 

  121. Tureen JH, Stella FB, Clyman RI, Mauray F, Sande MA (1987) Effect of indomethacin on brain water content, cerebrospinal fluid white blood cell response and prostaglandin E2 levels in experimental pneumococcal meningitis in rabbits. Fediatr Infect Dis J 6: 1151–1153

    Google Scholar 

  122. Tureen JH, Täuber MG, Sande MA (1991) Effect of indomethacin on the pathophysiology of experimental meningitis in rabbits. J Infect Dis 163: 647–649

    PubMed  Google Scholar 

  123. Tureen JH, Täuber MG, Sande MA (1992) Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis. J Clin Invest 89: 947–953

    PubMed  Google Scholar 

  124. Uchiyama N, Greene GR, Kitts DB, Thrupp LD (1980) Meningitis due toHaemophilus influenzae type b resistant to ampicillin and chloramphenicol. J Pediatr 97: 421–424

    PubMed  Google Scholar 

  125. Valone FH, Epstein LB (1988) Biphasic platelet-activating factor synthesis by human monocytes stimulated with IL-1β, tumor necrosis factor, or IFN-gamma. J Immunol 141: 3945–3950

    PubMed  Google Scholar 

  126. Waage A, Halstensen A, Shalaby R, Brandtzaeg P, Kierulf P, Espevik T (1989) Local production of tumor necrosis factor α, interleukin 1, and interleukin 6 in meningococcal meningitis. J Exp Med 170: 1859–1867

    Article  PubMed  Google Scholar 

  127. Wald E, US Meningitis Study Group (1992) Dexamethasone for children with bacterial meningitis (abstract 73). Program and abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Am Soc Microbiol, Washington, pp 123

    Google Scholar 

  128. Walterspiel JW, Kaplan SL, Mason EO (1986) Protective effect of subinhibitory polymyxin B alone and in combination with ampicillin for overwhelmingHaemophilus influenzae type b infection in the infant rat: evidence for in vivo and in vitro release of free endotoxin after ampicillin treatment. Pediatr Res 20: 237–241

    PubMed  Google Scholar 

  129. Watemberg N, Dagan R, Arbelli Y, Belmaker I, Morag A, Hessel L, Fritzell B, Bajard A, Peyron L (1991) Safety and immunogenicity ofHaemophilus influenzae type b-tetanus protein conjugate vaccine, mixed in the same syringe with diphtheria-tetanuspertussis vaccine in young infants. Pediatr Infect Dis J 10: 758–761

    PubMed  Google Scholar 

  130. Wenger JD, Hightower AW, Facklam RR, Gaventa S, Broome CV, and the Bacterial Meningitis Study group (1990) Bacterial meningitis in the United States, 1986: report of a multistate surveillance study. J Infect Dis 162: 1316–1323

    PubMed  Google Scholar 

  131. Wispelwey B, Lesse AJ, Hansen EJ, Scheld WM (1988) Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat. J Clin Invest 82: 1339–1346

    PubMed  Google Scholar 

  132. Wotton KA, Stiver HG, Hildes JA (1981) Meningitis in the central Arctic, a 4-year experience. Can Med Assoc J 124: 887–890

    PubMed  Google Scholar 

  133. Ziegler EJ, McCutchan JA, Fierer J, Glauser MP, Sadoff JC, Douglas H, Braude AI (1982) Treatment of gramnegative bacteremia and shock with human antiserum to a mutantEscherichia coli. N Engl J Med 307: 1225–1230

    PubMed  Google Scholar 

  134. Ziegler EJ, Fisher CJ, Sprung CL, Straube RC, Sadoff JC, Foulke GE, Wortel CH, Fink MP, Dellinger RP, Teng NNH, Allen IE, Berger HJ, Knatterud GL, LoBuglio AF, Smith CR, HA-1A Sepsis Study Group (1991) Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N Engl J Med 324: 429–436

    PubMed  Google Scholar 

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  1. Department of Paediatrics, Division of Immunology and Infectious Diseases, Sophia Children's Hospital, University Hospital Rotterdam, Dr. Molewaterplein 60, NL-3015 GJ, Rotterdam, The Netherlands

    R. F. Kornelisse, R. de Groot & H. J. Neijens

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Kornelisse, R.F., de Groot, R. & Neijens, H.J. Bacterial meningitis: Mechanisms of disease and therapy. Eur J Pediatr 154, 85–96 (1995). https://doi.org/10.1007/BF01991906

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