Laboratory Studies
- Definitive diagnosis of meningococcal infection requires culture of meningococci from blood, spinal fluid, joint fluid, or, occasionally, from skin lesions.
- Cultures produce transparent, nonpigmented colonies that are oxidase positive and nonhemolytic.
- The sensitivity of blood culture is 60%-80% in untreated patients.
- Cerebrospinal fluid (CSF) culture yields a sensitivity of up to 70% in untreated patients.
- Polymorphonuclear leukocyte levels are usually elevated, but they may be within the reference range or low.
- Thrombocytopenia may be present.
- In meningitis, the CSF can be turbid in appearance, with elevated pressures and proteins, and low glucose levels. In very early infections, CSF examination results may be normal.
- CSF Gram stain yields a sensitivity of approximately 50% in patients with meningococcal meningitis. It can have a higher yield than blood cultures.
- Detection of meningococcal capsular polysaccharide in CSF may be used for rapid diagnosis. It is sensitive for A and C polysaccharides.
- Gram-negative diplococci may be observed in punch biopsy and needle aspiration specimens of skin lesions or buffy coat preparations. Gram-negative diplococci may also be recovered from joint fluid. Findings on Gram stains of skin lesions remain positive for up to 2 days after the start of antibiotics and form a rapid means of diagnosis, including when meningitis is not present and when spinal fluid culture findings are negative owing to the administration of antibiotics. See the image shown below.
Gram-negative intracellular diplococci. Courtesy Professor Chien Liu. - Meningococcal polymerase chain reaction (PCR) is a rapid method for diagnosing CSF infection.[13] It may not be available commercially in the United States but has been used extensively in the United Kingdom. PCR of spinal fluid yields a sensitivity and specificity of more than 90% in the diagnosis of meningococcal meningitis. It is useful when antibiotics have been administered and can be used to rapidly type strains in developing epidemics. Diagnosis and serogrouping of N meningitidis infection can also be performed on formalin-fixed tissue samples using immunohistochemical analysis and PCR.[14, 15]
Imaging Studies
- Chest radiography is useful to evaluate for pneumonia and acute respiratory distress syndrome.
- Echocardiography can be used to evaluate for myocardial dysfunction and pericarditis.
Other Tests
- With serogrouping, polysaccharide antigens on the capsule are identified by a slide agglutination test using polyclonal antibodies.
- With serotyping and serosubtyping, outer membrane proteins (PorB and PorA) can be identified by an enzyme linked immunosorbent assay (ELISA) using monoclonal antibodies.
Procedures
- Lumbar puncture is used to test for meningitis.
- Appearance
- Measurement of pressure
- Stain and culture of fluid
- WBC count and differential
- Total protein level
- Glucose level
Staging
Evaluate for evidence of other end-organ damage (eg, kidney or hepatic failure) with appropriate blood tests.
MacLennan J, Kafatos G, Neal K, Andrews N, Cameron JC, Roberts R. Social behavior and meningococcal carriage in British teenagers. Emerg Infect Dis. Jun 2006;12(6):950-7. [Medline].
Livorsi DJ, Stenehjem E, Stephens DS. Virulence factors of gram-negative bacteria in sepsis with a focus on Neisseria meningitidis. Contrib Microbiol. 2011;17:31-47. [Medline].
Zughaier SM. Neisseria meningitidis capsular polysaccharides induce inflammatory responses via TLR2 and TLR4-MD-2. J Leukoc Biol. Mar 2011;89(3):469-80. [Medline]. [Full Text].
Plant L, Sundqvist J, Zughaier S, Lövkvist L, Stephens DS, Jonsson AB. Lipooligosaccharide structure contributes to multiple steps in the virulence of Neisseria meningitidis. Infect Immun. Feb 2006;74(2):1360-7. [Medline].
Davison KL, Ramsay ME. The epidemiology of acute meningitis in children in England and Wales. Arch Dis Child. Aug 2003;88(8):662-4. [Medline].
Wilder-Smith A. W135 meningococcal carriage in association with the Hajj pilgrimage 2001: the Singapore experience. Int J Antimicrob Agents. Feb 2003;21(2):112-5. [Medline].
Wilder-Smith A, Barkham TM, Earnest A, Paton NI. Acquisition of W135 meningococcal carriage in Hajj pilgrims and transmission to household contacts: prospective study. BMJ. Aug 17 2002;325(7360):365-6. [Medline].
Vyse A, Wolter JM, Chen J, Ng T, Soriano-Gabarro M. Meningococcal disease in Asia: an under-recognized public health burden. Epidemiol Infect. Apr 15 2011;1-19. [Medline]. [Full Text].
Wilder-Smith A, Chow A, Goh KT. Emergence and disappearance of W135 meningococcal disease. Epidemiol Infect. Jul 2010;138(7):976-8. [Medline].
Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. Jun 30 2007;369(9580):2196-210. [Medline].
Moura AS, Pablos-Méndez A, Layton M, Weiss D. Epidemiology of meningococcal disease, New York City, 1989-2000. Emerg Infect Dis. Mar 2003;9(3):355-61. [Medline].
Feldman HA. Meningococcal infections. Adv Intern Med. 1972;18:117-40. [Medline].
Dolan Thomas J, Hatcher CP, Satterfield DA, Theodore MJ, Bach MC, Linscott KB, et al. sodC-Based Real-Time PCR for Detection of Neisseria meningitidis. PLoS One. May 5 2011;6(5):e19361. [Medline]. [Full Text].
Guarner J, Greer PW, Whitney A, Shieh WJ, Fischer M, White EH, et al. Pathogenesis and diagnosis of human meningococcal disease using immunohistochemical and PCR assays. Am J Clin Pathol. Nov 2004;122(5):754-64. [Medline].
Fernández-Rodríguez A, Alcalá B, Alvarez-Lafuente R. Real-time polymerase chain reaction detection of Neisseria meningitidis in formalin-fixed tissues from sudden deaths. Diagn Microbiol Infect Dis. Apr 2008;60(4):339-46. [Medline].
Fraser A, Gafter-Gvili A, Paul M, Leibovici L. Prophylactic use of antibiotics for prevention of meningococcal infections: systematic review and meta-analysis of randomised trials. Eur J Clin Microbiol Infect Dis. Mar 2005;24(3):172-81. [Medline].
Licensure of a Meningococcal Conjugate Vaccine for Children Aged 2 Through 10 Years and Updated Booster Dose Guidance for Adolescents and Other Persons at Increased Risk for Meningococcal Disease --- Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. Aug 5 2011;60:1018-9. [Medline].
Licensure of a meningococcal conjugate vaccine (Menveo) and guidance for use - Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. Mar 12 2010;59(9):273. [Medline].
Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) vaccines for children - Factsheet. Available at http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_106052. Accessed 8/7/2011.
Updated recommendations for use of meningococcal conjugate vaccines --- Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. Jan 28 2011;60(3):72-6. [Medline].
Centers for Disease Control and Prevention (CDC). Update: Guillain-Barré syndrome among recipients of Menactra meningococcal conjugate vaccine--United States, June 2005-September 2006. MMWR Morb Mortal Wkly Rep. Oct 20 2006;55(41):1120-4. [Medline].
Alberio L, Lammle B, Esmon CT. Protein C replacement in severe meningococcemia: rationale and clinical experience. Clin Infect Dis. May 1 2001;32(9):1338-46. [Medline].
Barquet N, Domingo P, Cayla JA. Oral Antibiotics and Outcome in Meningococcemia. Arch Intern Med. Jul 24 2000;160(14):2220-2223. [Medline].
Brasier AR, Macklis JD, Vaughan D, et al. Myopericarditis as an initial presentation of meningococcemia. Unusual manifestation of infection with serotype W135. Am J Med. Mar 23 1987;82(3 Spec No):641-4. [Medline].
Busund R, Straume B, Revhaug A. Fatal course in severe meningococcemia: clinical predictors and effect of transfusion therapy. Crit Care Med. Nov 1993;21(11):1699-705. [Medline].
Davison KL, Andrews N, White JM, Ramsay ME, Crowcroft NS, Rushdy AA. Clusters of meningococcal disease in school and preschool settings in England and Wales: what is the risk?. Arch Dis Child. Mar 2004;89(3):256-60. [Medline].
Deutch S, Labouriau R, Schønheyeder HC, Ostergaard L, Nørgård B, Sørensen HT. Crowding as a risk factor of meningococcal disease in Danish preschool children: a nationwide population-based case-control study. Scand J Infect Dis. 2004;36(1):20-3. [Medline].
Drapkin MS, Wisch JS, Gelfand JA, et al. Plasmapheresis for fulminant meningococcemia. Pediatr Infect Dis J. Jun 1989;8(6):399-400. [Medline].
Dull PM, Abdelwahab J, Sacchi CT, et al. Neisseria meningitidis serogroup W-135 carriage among US travelers to the 2001 Hajj. J Infect Dis. Jan 1 2005;191(1):33-9. [Medline].
Dunlop KA, Coyle P, Mitchell S, Fairley D, O'Neill H, Jackson P, et al. Molecular testing of respiratory swabs aids early recognition of meningococcal disease in children. Diagn Microbiol Infect Dis. Aug 2011;70(4):427-34. [Medline].
El Ahmer OR, Essery SD, Saadi AT, et al. The effect of cigarette smoke on adherence of respiratory pathogens to buccal epithelial cells. FEMS Immunol Med Microbiol. Jan 1999;23(1):27-36. [Medline].
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].
Gjini AB, Stuart JM, Lawlor DA, Cartwright KA, Christensen H, Ramsay M. Changing epidemiology of bacterial meningitis among adults in England and Wales 1991-2002. Epidemiol Infect. Jun 2006;134(3):567-9. [Medline].
Grob H, Frei R, Tyndall A, Itin PH. [Chronic meningococcemia--a rare, but characteristic disease picture]. Schweiz Med Wochenschr. Dec 12 1998;128(50):1988-93. [Medline].
Hardy DJ, Bartholomew WR, Amsterdam D. Pathophysiology of primary meningococcal pericarditis associated with Neisseria meningitidis group C. A case report and review of the literature. Diagn Microbiol Infect Dis. Mar 1986;4(3):259-65. [Medline].
Heyderman RS, Ben-Shlomo Y, Brennan CA, Somerset M. The incidence and mortality for meningococcal disease associated with area deprivation: an ecological study of hospital episode statistics. Arch Dis Child. Nov 2004;89(11):1064-8. [Medline].
Hyszczak R, Bartold KP, Eggleston D. Gangrene associated with meningococcemia. AJR Am J Roentgenol. Jul 1988;151(1):203-4. [Medline].
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].
Leclerc F, Leteurtre S, Cremer R, et al. Do new strategies in meningococcemia produce better outcomes?. Crit Care Med. Sep 2000;28(9 Suppl):S60-3. [Medline].
Marotto MS, Marotto PC, Sztajnbok J, Seguro AC. Outcome of acute renal failure in meningococcemia. Ren Fail. Nov 1997;19(6):807-10. [Medline].
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].
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].
Pecoul B, Varaine F, Keita M, et al. Long-acting chloramphenicol versus intravenous ampicillin for treatment of bacterial meningitis. Lancet. Oct 5 1991;338(8771):862-6. [Medline].
Pereiro I, Diez-Domingo J, Segarra L, et al. Risk factors for invasive disease among children in Spain. J Infect. May 2004;48(4):320-9. [Medline].
Platonov AE, Beloborodov VB, Vershinina IV. [Clinical features of meningococcal infection in subjects with deficient terminal components of complement]. Ter Arkh. 1999;71(11):14-8. [Medline].
Riedo FX, Plikaytis BD, Broome CV. Epidemiology and prevention of meningococcal disease. Pediatr Infect Dis J. Aug 1995;14(8):643-57. [Medline].
Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal disease. N Engl J Med. May 3 2001;344(18):1378-88. [Medline].
Salzman MB, Rubin LG. Meningococcemia. Infect Dis Clin North Am. Dec 1996;10(4):709-25. [Medline].
Schaller RT Jr, Schaller JF. Surgical management of life-threatening and disfiguring sequelae of fulminant meningococcemia. Am J Surg. May 1986;151(5):553-6. [Medline].
Schlossberg D. Fever and rash. Infect Dis Clin North Am. Mar 1996;10(1):101-10. [Medline].
Singh J, Arrieta AC. Management of meningococcemia. Indian J Pediatr. Oct 2004;71(10):909-13. [Medline].
Tappero JW, Reporter R, Wenger JD, et al. Meningococcal disease in Los Angeles County, California, and among men in the county jails. N Engl J Med. Sep 19 1996;335(12):833-40. [Medline].
van Deuren M, van Dijke BJ, Koopman RJ, et al. Rapid diagnosis of acute meningococcal infections by needle aspiration or biopsy of skin lesions. BMJ. May 8 1993;306(6887):1229-32. [Medline].
Vienne P, Ducos-Galand M, Guiyoule A, et al. The role of particular strains of Neisseria meningitidis in meningococcal arthritis, pericarditis, and pneumonia. Clin Infect Dis. Dec 15 2003;37(12):1639-42. [Medline].
Welch SB, Nadel S. Treatment of meningococcal infection. Arch Dis Child. Jul 2003;88(7):608-14. [Medline].
White B, Livingstone W, Murphy C, et al. An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia. Blood. Dec 1 2000;96(12):3719-24. [Medline].

