Pediatric Meningococcal Infections Follow-up

  • Author: Saul N Faust, MA, MBBS, PhD, MRCPCH; Chief Editor: Russell W Steele, MD   more...
 
Updated: May 2, 2011
 

Further Inpatient Care

  • If shock or increased intracranial pressure (ICP) is present in patients with meningococcal infections, experienced staff should transfer the child to a pediatric intensive care unit as soon as possible.
  • Initially manage simple meningitis or sepsis that requires minimal intervention with regular cardiovascular (eg, pulse, blood pressure, capillary refill time) and neurological observation. Later, transfer the pediatric patient to a general medical pediatric ward if possible.
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Further Outpatient Care

Follow-up care at least 6 weeks after meningococcal infection should include the following:

  • Ongoing management of specific complications such as amputations, skin grafting, or renal failure
  • Full physical examination
  • Assessment of plasma complement levels (eg, total hemolytic complement, C3, and C4, with or without properdin)
  • Serological confirmation of the diagnosis if no diagnosis was made at the time of presentation
  • Audiologic function testing
  • Basic assessment psychological status after intensive care, if relevant
  • Possible vaccination of contacts if an outbreak of group A, C, Y, or W135 disease occurs
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Transfer

  • Transfer to a pediatric intensive care unit is necessary in approximately 20% of pediatric cases.
  • After extubation, transfer pediatric patients to a general pediatric ward.
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Deterrence/Prevention

  • Prevention of secondary cases
    • Household contacts of patients with meningococcal disease are 100-800 times more likely to contract the disease than the general population in the year after the index case. Risk of secondary cases in contacts decreases with time.
    • Chemoprophylaxis with rifampicin, ciprofloxacin, or ceftriaxone is currently offered to household and intimate contacts of the index case if meningococcal disease is suspected or proven. Ceftriaxone is preferred in children who refuse oral medication and may be used in pregnancy.
    • Current UK guidelines advise chemoprophylaxis be given only to household contacts (including those living or sleeping in the same house, pupils in the same dormitory, boyfriends/girlfriends, and university students sharing the same kitchen in halls of residence). Anyone who has had a transient close contact with the patient and has been directly exposed to respiratory secretions around the time of admission to the hospital should also receive prophylaxis. Other contacts do not require prophylaxis because the benefits of giving antibiotics in this setting are unknown; clusters in these settings are rare, and harm may arise from drug side effects, development of antibiotic resistance, and eradication of nonpathogenic organisms that may generate cross-protective immunity.
    • US guidelines recommend chemoprophylaxis be given to individuals in childcare facilities or nurseries who had contact with the patient in the 7 days before the illness onset and also be given to any contacts who have had direct exposure to secretions from the patient, such as kissing or sharing toothbrushes or eating utensils, during the 7 days before the illness onset. In addition, those who have frequently eaten or slept in the same dwelling as the patient in the preceding 7 days should be given prophylaxis.
    • Chemoprophylaxis is recommended for health care workers who are exposed to aerosol secretions from the patient (eg, those performing tracheal intubation) because they are 25 times more likely to contract the disease than the general population.
    • Because the rate of disease in secondary contacts is highest immediately after the onset of the disease in the patient, chemoprophylaxis should be administered as soon as possible, preferably within 24 hours. If chemoprophylaxis is delayed by more than 14 days, it is probably of limited value but is still recommended until 4 weeks after the patient's presentation.
    • Close contacts of patients with proven group C meningococcal infection should receive the protein-polysaccharide conjugate group C vaccine or the A/C polysaccharide vaccine.
    • Antibiotic chemoprophylaxis of N meningitides may involve the use of rifampicin, ceftriaxone, and/or ciprofloxacin (adults only).
  • Vaccination[27, 28]
    • Meningococci are gram-negative diplococci. Pathogenic strains are enveloped in a polysaccharide capsule, which facilitates invasion and which is an obvious target for candidate vaccines. The serogroup of the organism is assigned from the reaction of sera to the polysaccharide capsule.
    • Purified polysaccharide vaccines against encapsulated bacteria, such as meningococci, Haemophilus, and pneumococci, are poorly immunogenic in young children. Protein-polysaccharide conjugate vaccines for H influenzae type B are protective in infants and have greatly reduced the prevalence of disease caused by this organism.
    • The conjugate vaccine for group C meningococci contains serogroup C meningococcal polysaccharide is conjugated to the protein CRM197. It appears to be immunogenic in young children and was administered to all children during 1999-2000 in the United Kingdom. In January 2001, the short-term effectiveness of this vaccine in England was reported to be 97% (95% confidence interval [CI]: 77%, 99%) for teenagers and 92% (95% CI: 65%, 98%) for toddlers. These early results confirm the superiority of this vaccine compared with plain C polysaccharide vaccines, which are ineffective in young children.
    • The UK immunization schedule has recently changed to include a meningococcal booster at 12 months (combined with Hib booster) because studies showed that the efficacy of the vaccine declined at 1 year to around 80%.
    • In the United States, 2 meningococcal vaccines are available. MPSV4 (meningococcal polysaccharide vaccine) is recommended for use only in individuals aged 2-10 years who are at increased risk of meningococcal disease, such as those with terminal complement deficiencies and asplenia. The conjugate vaccine (MCV4) is also approved for individuals aged 9 months to 55 years who are at increased risk.[29] Additionally, the conjugate vaccine MCV4 is given to all children aged 11-12 years or at entry to high school or college if previously unvaccinated.
    • Purified polysaccharide is not a good immunogen in young children, and the previously approved meningococcal vaccines (A, C, Y, and W135 or A and C) are used only to protect travelers, for prophylaxis of household contacts of patients with proven serogroup C disease, or to control outbreaks of serogroup C disease in discrete communities.
    • Vaccines against group B serotypes are difficult to make. Because the polysaccharide capsule of the group B meningococcus is chemically and antigenically identical to human brain and fetal antigens, it is poorly immunogenic in humans, and its use might induce autoimmunity.
    • Other bacterial components, such as bacterial outer membrane proteins, are being investigated for use in vaccines. Vaccines have been prepared by using simple complexes of these proteins. Recent vaccines involve outer membrane vesicles and contain outer membrane proteins in spheres of the bacterial lipid membrane.
    • Although some serogroup B vaccine trials demonstrate an overall efficacy of more than 50%, protection for the most vulnerable age group has not been demonstrated. In those individuals with a detectable immune response, serum bactericidal activity after vaccination seems to be limited to the strain in the vaccine.
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Complications

Complications of meningococcal infection may include the following:

  • Cardiorespiratory failure that requires tracheal intubation and inotropic support
  • Renal failure that requires hemofiltration, hemodialysis, or peritoneal dialysis
  • Neurological failure
  • Severe peripheral gangrene that leads to skin grafting and (late) amputation
  • Peritoneal compartment syndrome due to severe abdominal capillary leak that requires placement of a tap
  • Immune complex disease leading to arthritis, pericarditis, myocarditis, and pneumonitis 10-14 days after the primary infection
  • Psychological disturbance after intensive care or complications
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Prognosis

  • A case-control study examined outcomes in adolescent patients and found that they had poorer mental health, social support, quality of life, and educational outcomes, as well as greater fatigue than well-matched controls.[30]
  • Isolated meningococcal meningitis (5% mortality rate) has a better prognosis than meningococcal septicemia (10-40% mortality rate).
  • Specialty units in geographical areas with a high incidence now have mortality rates of less than 5%.
  • In the United Kingdom, approximately 5% of survivors will have neurological sequelae, mainly sensorineural deafness. Amputation or skin grafting due to digital or limb ischaemia and severe skin necrosis may be required in 2-5% of survivors.
  • In the United States in 2005, a study reported 11-19% of survivors had serious health sequelae, including sensorineural hearing loss, amputations, and cognitive impairment.
  • A recent study from the Netherlands showed 35% of patients had some degree of neurological impairment; the largest proportion of these impairment symptoms was chronic headache.[31]
  • Another study from the Netherlands examined skin scarring and orthopaedic sequelae following meningococcal septic shock; 48% of children had skin scarring, ranging from extremely disfiguring scars to those that were barely visible, 14% of patients had orthopaedic sequelae, 8% had had amputations, and 6% had lower limb length discrepancy (more common in younger patients at age of meningococcal disease). Patients with scars or orthopaedic sequelae had significantly higher illness severity scores.[32]
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Patient Education

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Contributor Information and Disclosures
Author

Saul N Faust, MA, MBBS, PhD, MRCPCH  Senior Lecturer in Pediatric Immunology and Infectious Diseases, University of Southampton; Director, Wellcome Trust Clinical Research Facility, Southampton University Hospitals NHS Trust, UK

Saul N Faust, MA, MBBS, PhD, MRCPCH is a member of the following medical societies: British Paediatric Allergy, Immunology and Infectious Group, European Society for Paediatric Infectious Diseases, International Society for Infectious Diseases, and Royal College of Paediatrics and Child Health

Disclosure: Xoma Consulting fee Consulting; GSK Honoraria Consulting; Wyeth travel and registration fee to conference investigator in study being presented at meeting; Sanofi Pasteur Consulting fee Consulting; Pfizer Consulting fee Consulting

Coauthor(s)

Katrina Cathie, BM(Hons), MRCPCH  Academic Clinical Fellow, Southampton University, UK

Katrina Cathie, BM(Hons), MRCPCH is a member of the following medical societies: Royal College of Paediatrics and Child Health

Disclosure: Nothing to disclose.

Michael Levin, PhD, FRCP, FRCPCH  Head, Professor, Imperial College School of Medicine at St Mary's Hospital, Department of Pediatrics, London, England

Disclosure: Nothing to disclose.

Specialty Editor Board

David Jaimovich, MD  Chief Medical Officer, Joint Commission International and Joint Commission Resources

David Jaimovich, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Joseph Domachowske, MD  Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert W Tolan Jr, MD  Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility

Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Sanofi Pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD  Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

References

  1. Pollard AJ, Nadel S, Ninis N, Faust SN, Levin M. Emergency management of meningococcal disease: eight years on. Arch Dis Child. Apr 2007;92(4):283-6. [Medline]. [Full Text].

  2. Pathan N, Faust SN, Levin M. Pathophysiology of meningococcal meningitis and septicaemia. Arch Dis Child. Jul 2003;88(7):601-7. [Medline]. [Full Text].

  3. Faust SN, Levin M, Harrison OB, et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med. Aug 9 2001;345(6):408-16. [Medline].

  4. Pathan N, Hemingway CA, Alizadeh AA, et al. Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock. Lancet. Jan 17 2004;363(9404):203-9. [Medline].

  5. Pathan N, Williams EJ, Oragui EE, Stephens AC, Levin M. Changes in the interleukin-6/soluble interleukin-6 receptor axis in meningococcal septic shock. Crit Care Med. Aug 2005;33(8):1839-44. [Medline].

  6. El Bashir H, Laundy M, Booy R. Diagnosis and treatment of bacterial meningitis. Arch Dis Child. Jul 2003;88(7):615-20. [Medline]. [Full Text].

  7. Ortega-Sanchez IR, Meltzer MI, Shepard C, et al. Economics of an adolescent meningococcal conjugate vaccination catch-up campaign in the United States. Clin Infect Dis. Jan 1 2008;46(1):1-13. [Medline].

  8. Health Protection Agency. Invasive meningococcal infections, England and Wales, laboratory reports: weeks 51-52/2007. http://hpa.org.uk: 2008. [Full Text].

  9. Welch SB, Nadel S. Treatment of meningococcal infection. Arch Dis Child. Jul 2003;88(7):608-14. [Medline]. [Full Text].

  10. Jansen AG, Sanders EA, VAN DER Ende A, VAN Loon AM, Hoes AW, Hak E. Invasive pneumococcal and meningococcal disease: association with influenza virus and respiratory syncytial virus activity?. Epidemiol Infect. Nov 2008;136(11):1448-54. [Medline]. [Full Text].

  11. Faber J, Henninger N, Finn A, Zenz W, Zepp F, Knuf M. A toll-like receptor 4 variant is associated with fatal outcome in children with invasive meningococcal disease. Acta Paediatr. Mar 2009;98(3):548-52. [Medline].

  12. Darton T, Guiver M, Naylor S, Jack DL, Kaczmarski EB, Borrow R. Severity of meningococcal disease associated with genomic bacterial load. Clin Infect Dis. Mar 1 2009;48(5):587-94. [Medline].

  13. [Guideline] Health Protection Agency. Guidance for the public health management of meningococcal disease in the UK. [Full Text].

  14. Food and Drug Administration. Ceftriaxone (marketed as Rocephin) information. 2008. [Full Text].

  15. Roche. Important clarification of prescribing information. Contraindications. http://www.rocheusa.com. Available at http://www.rocheusa.com/products/rocephin/rocephin-hcp-letter.pdf. Accessed August 5, 2008.

  16. Medicines and healthcare products regulatory agency. Ceftriaxone; incompatibility with calcium containing solutions. http://www.nelm.nhs.uk/en/: 2008.

  17. Food and Drug Administration. Ceftriaxone (marketed as Rocephin) Information. http://www.fda.gov: April 2009. [Full Text].

  18. Cathie K, Levin M, Faust SN. Drug use in acute meningococcal disease. Arch Dis Child Educ Pract Ed. Oct 2008;93(5):151-8. [Medline].

  19. Levin M, Quint PA, Goldstein B, et al. Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group. Lancet. Sep 16 2000;356(9234):961-7. [Medline].

  20. Derkx B, Wittes J, McCloskey R. Randomized, placebo-controlled trial of HA-1A, a human monoclonal antibody to endotoxin, in children with meningococcal septic shock. European Pediatric Meningococcal Septic Shock Trial Study Group. Clin Infect Dis. Apr 1999;28(4):770-7. [Medline].

  21. de Kleijn ED, de Groot R, Hack CE, et al. Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: a randomized, double-blinded, placebo-controlled, dose-finding study. Crit Care Med. Jun 2003;31(6):1839-47. [Medline].

  22. [Best Evidence] Nadel S, Goldstein B, Williams MD, et al. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet. Mar 10 2007;369(9564):836-43. [Medline].

  23. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K. Hydrocortisone therapy for patients with septic shock. N Engl J Med. Jan 10 2008;358(2):111-24. [Medline].

  24. Jaeschke R, Angus DC. Living with uncertainty in the intensive care unit: should patients with sepsis be treated with steroids?. JAMA. Jun 10 2009;301(22):2388-90. [Medline].

  25. Vincent JL, Abraham E, Annane D, Bernard G, Rivers E, Van den Berghe G. Reducing mortality in sepsis: new directions. Crit Care. Dec 2002;6 Suppl 3:S1-18. [Medline].

  26. Day KM, Haub N, Betts H, Inwald DP. Hyperglycemia is associated with morbidity in critically ill children with meningococcal sepsis. Pediatr Crit Care Med. Nov 2008;9(6):636-40. [Medline].

  27. Bethell D, Pollard AJ. Meningococcal vaccines. Expert Rev Vaccines. Jun 2002;1(1):75-84. [Medline].

  28. Pollard AJ. Global epidemiology of meningococcal disease and vaccine efficacy. Pediatr Infect Dis J. Dec 2004;23(12 Suppl):S274-9. [Medline].

  29. FDA News Release. FDA approves the first vaccine to prevent meningococcal disease in infants and toddlers. April 22, 2011. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm252392.htm. Accessed April 27, 2011.

  30. Borg J, Christie D, Coen PG, Booy R, Viner RM. Outcomes of meningococcal disease in adolescence: prospective, matched-cohort study. Pediatrics. Mar 2009;123(3):e502-9. [Medline]. [Full Text].

  31. Buysse CM, Raat H, Hazelzet JA, et al. Long-term health status in childhood survivors of meningococcal septic shock. Arch Pediatr Adolesc Med. Nov 2008;162(11):1036-41. [Medline]. [Full Text].

  32. Buysse CM, Oranje AP, Zuidema E, et al. Long-term skin scarring and orthopaedic sequelae in survivors of meningococcal septic shock. Arch Dis Child. May 2009;94(5):381-6. [Medline].

  33. Advanced Life Support Group. Relative contraindications to lumbar puncture. In: Advanced Paediatric Life Support: The Practical Approach. London, England: BMJ Publishing; 1997:127.

  34. Albanesi Filho FM, Rocha RM, Barros RA. Meningococcemia complicated by myocarditis. Arq Bras Cardiol. Feb 1998;70(2):115-8. [Medline].

  35. Baker RC, Seguin JH, Leslie N, et al. Fever and petechiae in children. Pediatrics. Dec 1989;84(6):1051-5. [Medline].

  36. Begg N, Cartwright KA, Cohen J, et al. Consensus statement on diagnosis, investigation, treatment and prevention of acute bacterial meningitis in immunocompetent adults. British Infection Society Working Party. J Infect. Jul 1999;39(1):1-15. [Medline].

  37. Borrow R, Fox AJ, Cartwright K, Begg NT, Jones DM. Salivary antibodies following parenteral immunization of infants with a meningococcal serogroup A and C conjugated vaccine. Epidemiol Infect. Oct 1999;123(2):201-8. [Medline]. [Full Text].

  38. Boucek MM, Boerth RC, Artman M, et al. Myocardial dysfunction in children with acute meningococcemia. J Pediatr. Oct 1984;105(4):538-42. [Medline].

  39. Brandtzaeg P, Sandset PM, Joo GB, et al. The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic pathway inhibitor and fibrinopeptide A in systemic meningococcal disease. Thromb Res. Aug 15 1989;55(4):459-70. [Medline].

  40. Breiman RF, Butler JC, Tenover FC, et al. Emergence of drug-resistant pneumococcal infections in the United States. JAMA. Jun 15 1994;271(23):1831-5. [Medline].

  41. Butler JC, Dowell SF, Breiman RF. Epidemiology of emerging pneumococcal drug resistance: implications for treatment and prevention. Vaccine. Nov 1998;16(18):1693-7. [Medline].

  42. Cartwright K. Risk factors for meningococcal disease. In: Meningococcal Disease. John Wiley & Sons; 1995:126-38.

  43. Cartwright K, Kroll S. Optimising the investigation of meningococcal disease. BMJ. Sep 27 1997;315(7111):757-8. [Medline]. [Full Text].

  44. Cartwright K, Morris R, Rumke H, et al. Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins. Vaccine. Jun 4 1999;17(20-21):2612-9. [Medline].

  45. Cartwright K, Reilly S, White D, Stuart J. Early treatment with parenteral penicillin in meningococcal disease. BMJ. Jul 18 1992;305(6846):143-7. [Medline]. [Full Text].

  46. Cartwright KA. Early management of meningococcal disease. Infect Dis Clin North Am. Sep 1999;13(3):661-84, viii. [Medline].

  47. Cartwright KA, Jones DM, Smith AJ, et al. Influenza A and meningococcal disease. Lancet. Aug 31 1991;338(8766):554-7. [Medline].

  48. Caugant DA, Hoiby EA, Magnus P, Scheel O, Hoel T, Bjune G, et al. Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population. J Clin Microbiol. Feb 1994;32(2):323-30. [Medline]. [Full Text].

  49. CDR. Vaccination programme for group C meningococcal disease is launched. Comm Dis Rep. 1999;9(30):261-64.

  50. Collen D. The plasminogen (fibrinolytic) system. Thromb Haemost. Aug 1999;82(2):259-70. [Medline].

  51. Cooke RP, Riordan T, Jones DM, Painter MJ. Secondary cases of meningococcal infection among close family and household contacts in England and Wales, 1984-7. BMJ. Mar 4 1989;298(6673):555-8. [Medline]. [Full Text].

  52. de Jonge E, Levi M, Stoutenbeek CP, van Deventer SJ. Current drug treatment strategies for disseminated intravascular coagulation. Drugs. Jun 1998;55(6):767-77. [Medline].

  53. Dixon GL, Heyderman RS, Kotovicz K, Jack DL, Andersen SR, Vogel U, et al. Endothelial adhesion molecule expression and its inhibition by recombinant bactericidal/permeability-increasing protein are influenced by the capsulation and lipooligosaccharide structure of Neisseria meningitidis. Infect Immun. Nov 1999;67(11):5626-33. [Medline]. [Full Text].

  54. Drake TA, Cheng J, Chang A, Taylor FB Jr. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol. May 1993;142(5):1458-70. [Medline]. [Full Text].

  55. Dreyfus M, Magny JF, Bridey F, et al. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med. Nov 28 1991;325(22):1565-8. [Medline].

  56. Duffy GP. Lumbar puncture in the presence of raised intracranial pressure. Br Med J. Feb 15 1969;1(5641):407-9. [Medline]. [Full Text].

  57. Erlich J, Fearns C, Mathison J, Ulevitch RJ, Mackman N. Lipopolysaccharide induction of tissue factor expression in rabbits. Infect Immun. May 1999;67(5):2540-6. [Medline]. [Full Text].

  58. Esmon CT. Blood coagulation. In: Lampert R, ed. Nathan and Orkin's Hematology of Infancy and Childhood. Harcourt Health Sciences; 1998:1531-52.

  59. Esmon CT, Ding W, Yasuhiro K, et al. The protein C pathway: new insights. Thromb Haemost. Jul 1997;78(1):70-4. [Medline].

  60. Esmon CT, Fukudome K, Mather T, et al. Inflammation, sepsis, and coagulation. Haematologica. Mar 1999;84(3):254-9. [Medline].

  61. Esmon CT, Xu J, Gu JM, et al. Endothelial protein C receptor. Thromb Haemost. Aug 1999;82(2):251-8. [Medline].

  62. Faust SN, Heyderman RS, Levin M. Disseminated intravascular coagulation and purpura fulminans secondary to infection. Baillieres Best Pract Res Clin Haematol. Jun 2000;13(2):179-97. [Medline].

  63. Finn A, Booy R, Levin M, et al. Infectious purpura fulminans: caution needed in the use of protein C. Br J Haematol. Jul 1999;106(1):253-4. [Medline].

  64. Fishman RA. Lumbar puncture. In: Oxford Textbook of Medicine. 3rd ed. Oxford University Press; 1995.

  65. Fitton AR, Dickson WA, Shortland G, Smithies M. Peripheral gangrene associated with fulminating meningococcal septicaemia. Is early escharotomy indicated?. J Hand Surg [Br]. Jun 1997;22(3):408-10. [Medline].

  66. Fourrier F, Lestavel P, Chopin C, et al. Meningococcemia and purpura fulminans in adults: acute deficiencies of proteins C and S and early treatment with antithrombin III concentrates. Intensive Care Med. 1990;16(2):121-4. [Medline].

  67. Fukudome K, Esmon CT. Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem. Oct 21 1994;269(42):26486-91. [Medline]. [Full Text].

  68. Goitein KJ, Tamir I. Cerebral perfusion pressure in central nervous system infections of infancy and childhood. J Pediatr. Jul 1983;103(1):40-3. [Medline].

  69. Gregory SA, Morrissey JH, Edgington TS. Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol. Jun 1989;9(6):2752-5. [Medline]. [Full Text].

  70. Grocott-Mason RM, Shah AM. Cardiac dysfunction in sepsis: new theories and clinical implications. Intensive Care Med. Apr 1998;24(4):286-95. [Medline].

  71. Hajjar. The molecular basis of fibrinolysis. In: Lampert R, ed. Nathan and Orkin's Hematology of Infancy and Childhood. Harcourt Health Sciences; 1998.

  72. Havens PL, Garland JS, Brook MM, et al. Trends in mortality in children hospitalized with meningococcal infections, 1957 to 1987. Pediatr Infect Dis J. Jan 1989;8(1):8-11. [Medline].

  73. Hazelzet JA, Risseeuw-Appel IM, Kornelisse RF, et al. Age-related differences in outcome and severity of DIC in children with septic shock and purpura. Thromb Haemost. Dec 1996;76(6):932-8. [Medline].

  74. Hermans PW, Hibberd ML, Booy R, et al. 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Meningococcal Research Group. Lancet. Aug 14 1999;354(9178):556-60. [Medline].

  75. Heyderman RS, Ison CA, Peakman M, et al. Neutrophil response to Neisseria meningitidis: inhibition of adhesion molecule expression and phagocytosis by recombinant bactericidal/permeability-increasing protein (rBPI21). J Infect Dis. May 1999;179(5):1288-92. [Medline].

  76. Heyderman RS, Klein NJ, Shennan GI, Levin M. Deficiency of prostacyclin production in meningococcal shock. Arch Dis Child. Nov 1991;66(11):1296-9. [Medline]. [Full Text].

  77. Heyderman RS, Klein NJ, Shennan GI, Levin M. Reduction of the anticoagulant activity of glycosaminoglycans on the surface of the vascular endothelium by endotoxin and neutrophils: evaluation by an amidolytic assay. Thromb Res. Sep 15 1992;67(6):677-85. [Medline].

  78. Hibberd ML, Sumiya M, Summerfield JA, et al. Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group. Lancet. Mar 27 1999;353(9158):1049-53. [Medline].

  79. Ho G, Broze GJ Jr, Schwartz AL. Role of heparan sulfate proteoglycans in the uptake and degradation of tissue factor pathway inhibitor-coagulation factor Xa complexes. J Biol Chem. Jul 4 1997;272(27):16838-44. [Medline]. [Full Text].

  80. Hodgetts TJ, Brett A, Castle N. The early management of meningococcal disease. J Accid Emerg Med. Mar 1998;15(2):72-6. [Medline]. [Full Text].

  81. Kirsch EA, Barton RP, Kitchen L, Giroir BP. Pathophysiology, treatment and outcome of meningococcemia: a review and recent experience. Pediatr Infect Dis J. Nov 1996;15(11):967-78; quiz 979. [Medline].

  82. Kitchens CS. Disseminated intravascular coagulation. Curr Opin Hematol. Sep 1995;2(5):402-6. [Medline].

  83. Klein NJ, Ison CA, Peakman M, et al. The influence of capsulation and lipooligosaccharide structure on neutrophil adhesion molecule expression and endothelial injury by Neisseria meningitidis. J Infect Dis. Jan 1996;173(1):172-9. [Medline].

  84. Klein NJ, Shennan GI, Heyderman RS, Levin M. Alteration in glycosaminoglycan metabolism and surface charge on human umbilical vein endothelial cells induced by cytokines, endotoxin and neutrophils. J Cell Sci. Aug 1992;102 ( Pt 4):821-32. [Medline]. [Full Text].

  85. Kondaveeti S, Hibberd ML, Booy R, et al. Effect of the Factor V Leiden mutation on the severity of meningococcal disease. Pediatr Infect Dis J. Oct 1999;18(10):893-6. [Medline].

  86. Kondaveeti S, Hibberd ML, Levin M. The insertion/deletion polymorphism in the t-PA gene does not significantly affect outcome of meningococcal disease. Thromb Haemost. Jul 1999;82(1):161-2. [Medline].

  87. Kornelisse RF, Hazelzet JA, Hop WC, et al. Meningococcal septic shock in children: clinical and laboratory features, outcome, and development of a prognostic score. Clin Infect Dis. Sep 1997;25(3):640-6. [Medline].

  88. Kornelisse RF, Hazelzet JA, Savelkoul HF, et al. The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock. J Infect Dis. May 1996;173(5):1148-56. [Medline].

  89. Lee KH, Hui KP, Tan WC. Thrombocytopenia in sepsis: a predictor of mortality in the intensive care unit. Singapore Med J. Jun 1993;34(3):245-6. [Medline].

  90. Levin M, Eley BS, Louis J, et al. Postinfectious purpura fulminans caused by an autoantibody directed against protein S. J Pediatr. Sep 1995;127(3):355-63. [Medline].

  91. Levin M, Galassini R, de Munter C. Improved survival in children admitted to intensive care with meningococcal disease: Proceedings of the Royal College of Paediatrics and Child Health Annual. 1998:98.

  92. Levin M, Nadel S. Bacterial meningitis: pathophysiology and causes and therapeutic approach. In: Oxford Textbook of Critical Care. Oxford University Press; 1999.

  93. Lynn WA. Anti-endotoxin therapeutic options for the treatment of sepsis. J Antimicrob Chemother. Jan 1998;41 Suppl A:71-80. [Medline].

  94. Mackman N. Regulation of the tissue factor gene. Thromb Haemost. Jul 1997;78(1):747-54. [Medline].

  95. Madden RM, Gill JC, Marlar RA. Protein C and protein S levels in two patients with acquired purpura fulminans. Br J Haematol. May 1990;75(1):112-7. [Medline].

  96. Mandl KD, Stack AM, Fleisher GR. Incidence of bacteremia in infants and children with fever and petechiae. J Pediatr. Sep 1997;131(3):398-404. [Medline].

  97. Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost. Aug 1999;82(2):165-74. [Medline].

  98. Marzouk O, Thomson AP, Sills JA, Hart CA, Harris F. Features and outcome in meningococcal disease presenting with maculopapular rash. Arch Dis Child. Apr 1991;66(4):485-7. [Medline]. [Full Text].

  99. McIntyre PB, Berkey CS, King SM, et al. Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988. JAMA. Sep 17 1997;278(11):925-31. [Medline].

  100. Meningococcal Disease Surveillance Group. Analysis of endemic meningococcal disease by serogroup and evaluation of chemoprophylaxis. J Infect Dis. Aug 1976;134(2):201-4. [Medline].

  101. Meszaros K, Aberle S, Dedrick R, et al. Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein. Blood. May 1 1994;83(9):2516-25. [Medline]. [Full Text].

  102. Monsalve F, Rucabado L, Salvador A, et al. Myocardial depression in septic shock caused by meningococcal infection. Crit Care Med. Dec 1984;12(12):1021-3. [Medline].

  103. Nadel S, Britto J, Booy R, Maconochie I, Habibi P, Levin M. Avoidable deficiencies in the delivery of health care to children with meningococcal disease. J Accid Emerg Med. Sep 1998;15(5):298-303. [Medline]. [Full Text].

  104. Nadel S, Joarder R, Gibson M, Stevens J, Britto J, Habibi P, et al. Emergency cranial computed tomography in the management of acute febrile encephalopathy in children. J Accid Emerg Med. Nov 1999;16(6):403-6. [Medline]. [Full Text].

  105. Nadel S, Levin M, Habibi P. Treatment of meningococcal disease in childhood. In: Meningococcal Disease. John Wiley & Sons; 1995:207-43.

  106. Nadel S, Marriage S, De Munter C, et al. Human albumin administration in critically ill patients. Review did not provide recommendations for alternative treatment. BMJ. Sep 26 1998;317(7162):882-3. [Medline].

  107. Nesheim M, Wang W, Boffa M, et al. Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thromb Haemost. Jul 1997;78(1):386-91. [Medline].

  108. Ni H, Knight AI, Cartwright K, et al. Polymerase chain reaction for diagnosis of meningococcal meningitis. Lancet. Dec 12 1992;340(8833):1432-4. [Medline].

  109. Ninis N, Phillips C, Bailey L, Pollock JI, Nadel S, Britto J, et al. The role of healthcare delivery in the outcome of meningococcal disease in children: case-control study of fatal and non-fatal cases. BMJ. Jun 25 2005;330(7506):1475. [Medline]. [Full Text].

  110. Osterud B, Flaegstad T. Increased tissue thromboplastin activity in monocytes of patients with meningococcal infection: related to an unfavourable prognosis. Thromb Haemost. Feb 28 1983;49(1):5-7. [Medline].

  111. Paramo JA, Fernandez Diaz FJ, Rocha E. Plasminogen activator inhibitor activity in bacterial infection. Thromb Haemost. Jun 16 1988;59(3):451-4. [Medline].

  112. Paramo JA, Perez JL, Serrano M, Rocha E. Types 1 and 2 plasminogen activator inhibitor and tumor necrosis factor alpha in patients with sepsis. Thromb Haemost. Aug 13 1990;64(1):3-6. [Medline].

  113. Parker MM. Pathophysiology of cardiovascular dysfunction in septic shock. New Horiz. May 1998;6(2):130-8. [Medline].

  114. Parrillo JE, Parker MM, Natanson C, et al. Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med. Aug 1 1990;113(3):227-42. [Medline].

  115. Pathan N, Faust SN, Levin M. Pathophysiology of meningococcal meningitis and septicaemia. Arch Dis Child. Jul 2003;88(7):601-7. [Medline]. [Full Text].

  116. Peltola H, Anttila M, Renkonen OV. Randomised comparison of chloramphenicol, ampicillin, cefotaxime, and ceftriaxone for childhood bacterial meningitis. Finnish Study Group. Lancet. Jun 10 1989;1(8650):1281-7. [Medline].

  117. Peter G, Weigert MB, Bissel AR, et al. Meningococcal meningitis in familial deficiency of the fifth component of complement. Pediatrics. Jun 1981;67(6):882-6. [Medline].

  118. Peters MJ, Dixon G, Kotowicz KT, et al. Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing. Br J Haematol. Aug 1999;106(2):391-9. [Medline].

  119. Pfister HW, Borasio GD, Dirnagl U, et al. Cerebrovascular complications of bacterial meningitis in adults. Neurology. Aug 1992;42(8):1497-504. [Medline].

  120. PHLS Meningococcal Infections Working Group and, Public Health Medicine Environmental Group. Control of meningococcal disease: guidance for consultants in communicable disease control. Commun Dis Rep CDR Rev. Dec 8 1995;5(13):R189-95. [Medline].

  121. Piper RD. Myocardial dysfunction in sepsis. Clin Exp Pharmacol Physiol. Nov 1998;25(11):951-4. [Medline].

  122. Pollard AJ, Begg N. Meningococcal disease and healthcare workers. BMJ. Oct 30 1999;319(7218):1147-8. [Medline]. [Full Text].

  123. Pollard AJ, Faust SN, Levin M. Meningitis and meningococcal septicaemia. J R Coll Physicians Lond. Jul-Aug 1998;32(4):319-28. [Medline].

  124. Pollard AJ, Galassini R, Rouppe van der Voort EM, Hibberd M, Booy R, Langford P, et al. Cellular immune responses to Neisseria meningitidis in children. Infect Immun. May 1999;67(5):2452-63. [Medline]. [Full Text].

  125. Ramsay ME, Andrews N, Kaczmarski EB, et al. Efficacy of meningococcal serogroup C conjugate vaccine in teenagers and toddlers in England. Lancet. Jan 20 2001;357(9251):195-6. [Medline].

  126. Rennick G, Shann F, de Campo J. Cerebral herniation during bacterial meningitis in children. BMJ. Apr 10 1993;306(6883):953-5. [Medline]. [Full Text].

  127. Richmond P, Borrow R, Miller E, et al. Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory. J Infect Dis. Jun 1999;179(6):1569-72. [Medline].

  128. Riordan T, Cartwright K, Andrews N, Stuart J, Burris A, Fox A, et al. Acquisition and carriage of meningococci in marine commando recruits. Epidemiol Infect. Dec 1998;121(3):495-505. [Medline]. [Full Text].

  129. Rivard GE, David M, Farrell C, Schwarz HP. Treatment of purpura fulminans in meningococcemia with protein C concentrate. J Pediatr. Apr 1995;126(4):646-52. [Medline].

  130. Rosenstein NE, Perkins BA, Stephens DS, et al. The changing epidemiology of meningococcal disease in the United States, 1992-1996. J Infect Dis. Dec 1999;180(6):1894-901. [Medline].

  131. Saez-Nieto JA, Lujan R, Berron S, et al. Epidemiology and molecular basis of penicillin-resistant Neisseria meningitidis in Spain: a 5-year history (1985-1989). Clin Infect Dis. Feb 1992;14(2):394-402. [Medline].

  132. Schaad UB, Kaplan SL, McCracken GH Jr. Steroid therapy for bacterial meningitis. Clin Infect Dis. Mar 1995;20(3):685-90. [Medline].

  133. Schmutzhard E, Williams KJ, Vukmirovits G, et al. A randomised comparison of meropenem with cefotaxime or ceftriaxone for the treatment of bacterial meningitis in adults. Meropenem Meningitis Study Group. J Antimicrob Chemother. Jul 1995;36 Suppl A:85-97. [Medline].

  134. Shinefield HR, Black S, Ray P, et al. Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers. Pediatr Infect Dis J. Sep 1999;18(9):757-63. [Medline].

  135. Smith OP, White B. Infectious purpura fulminans: diagnosis and treatment. Br J Haematol. Feb 1999;104(2):202-7. [Medline].

  136. Smith OP, White B, Vaughan D, et al. Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans. Lancet. Nov 29 1997;350(9091):1590-3. [Medline].

  137. Taylor FB Jr, Chang A, Esmon CT, et al. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest. Mar 1987;metabolism(3):918-25. [Medline].

  138. Tunkel AR, Scheld WM. Acute bacterial meningitis. Lancet. Dec 23-30 1995;346(8991-8992):1675-80. [Medline].

  139. Tunkel AR, Scheld WM. Pathogenesis and pathophysiology of bacterial meningitis. Annu Rev Med. 1993;44:103-20. [Medline].

  140. Tunkel AR, Scheld WM. Acute meningitis. In: Principles and Practice of Infectious Diseases. 4th ed. Churchill Livingstone; 1995:831-65.

  141. Tureen JH, Täuber MG, Sande MA. Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis. J Clin Invest. Mar 1992;89(3):947-53. [Medline]. [Full Text].

  142. van 't Veer C, Golden NJ, Kalafatis M, Mann KG. Inhibitory mechanism of the protein C pathway on tissue factor-induced thrombin generation. Synergistic effect in combination with tissue factor pathway inhibitor. J Biol Chem. Mar 21 1997;272(12):7983-94. [Medline].

  143. Van Nguyen Q, Nguyen EA, Weiner LB. Incidence of invasive bacterial disease in children with fever and petechiae. Pediatrics. Jul 1984;74(1):77-80. [Medline].

  144. Weatherall DJ. Host genetics and infectious disease. Parasitology. 1996;112 Suppl:S23-9. [Medline].

  145. Westendorp RG, Hottenga JJ, Slagboom PE. Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock. Lancet. Aug 14 1999;354(9178):561-3. [Medline].

  146. Westendorp RG, Langermans JA, Huizinga TW, et al. Genetic influence on cytokine production and fatal meningococcal disease. Lancet. Jan 18 1997;349(9046):170-3. [Medline].

  147. World Health Organization. Meningogoccal meningitis. Indian J Med Sci. Aug 2003;57(8):369-72. [Medline].

  148. Young LS, LaForce FM, Head JJ, et al. A simultaneous outbreak of meningococcal and influenza infections. N Engl J Med. Jul 6 1972;287(1):5-9. [Medline].

 
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Child with severe meningococcal disease and purpura fulminans.
Flowchart shows guidelines for the emergency management of meningococcal disease in children. These guidelines may be reprinted for use in clinical areas and are available at Meningitis.org.
Flowchart shows guidelines for the emergency management of meningococcal disease in adult patients. These guidelines may be reprinted for use in clinical areas and are available from Meningitis.org.
Chart for family practice recognition and management of meningococcal disease (courtesy of Meningitis.org).
Family practice booklet describing management of meningococcal disease in the community (courtesy of Meningitis.org).
 
 
 
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