Pediatric Infectious Disease

Register      Login

VOLUME 1 , ISSUE 3 ( July-September, 2019 ) > List of Articles


Invasive Meningococcal Disease: A Review

Rashna D Hazarika

Keywords : Invasive meningococcal disease, Meningitis, Meningococcemia, Neisseria, Purpura fulminans, Shock

Citation Information : Hazarika RD. Invasive Meningococcal Disease: A Review. Pediatr Inf Dis 2019; 1 (3):95-107.

DOI: 10.5005/jp-journals-10081-1215

License: CC BY-NC 4.0

Published Online: 05-09-2020

Copyright Statement:  Copyright © 2019; The Author(s).


Background: Invasive meningococcal disease (IMD) is a potentially fatal disease occurring all over the world. It affects predominantly young children, adolescents and young adults. However, even today cases are missed and there may be a delay in diagnosis and treatment leading not only to a fatal outcome but also to large scale epidemics. Materials and methods: An extensive review of literature was done to describe the history, microbiology, global epidemiology, transmission and risk factors, pathogenesis, clinical features, management, prognosis, care of relatives and close contacts, prevention by the current vaccines available in the world and in India. Results: Invasive meningococcal disease was first described in 1805 in Sweden. Subsequently periodic epidemics continue to occur all over the world. Globally it is present in more than 80 countries. Currently 12 known serotypes are described with a complex microbiology which helps the bacteria to not only survive in the human nasopharynx but also to adhere to and invade the meninges and the blood stream and present as meningitis, meningococcemia or both. Due to its capacity to produce various toxins and ability to survive destruction by the host immune system, it produces a number of clinical manifestations in a short time. Being potentially fatal, death in such patients can occur in a matter of hours. Microbiological diagnosis is difficult as the organism is fastidious and requires special conditions for growth and can explain the poor microbiological results worldwide. However attempts to culture the bacteria should be made from all available sites such as cerebrospinal fluid, blister fluid, blood and even skin biopsy specimen. The cornerstone of management is aggressive treatment with antibiotics, and other supportive care. Complications are common during the course of the infection and one must anticipate and tackle them aggressively and at the appropriate time. A large number of sequelae can occur in spite of optimal management. Prophylactic antibiotics in the care-givers and relatives is extremely important for short term protection. Long term protection of the community as well as of care-givers and close relatives is by vaccination. A number of effective vaccines have been developed over the years for the prevention of this deadly infection. Vaccine cost remains a major hindrance to universal vaccination. Conclusion: Invasive meningococcal disease exists all over the world. It is important to be able to correctly recognize these patients for early and aggressive management. Prevention by vaccination remains the best public health measure to tackle this deadly infection.

PDF Share
  1. Jafri RZ, Ali A, Messonnier NE, et al. Global epidemiology of invasive meningococcal disease. Popul Health Metr 2013;11(1):17. DOI: 10.1186/1478-7954-11-17.
  2. Vieusseux M. Mémoire sur la maladie qui a regné a Genêve au printemps de 1805. J Med Chir Pharmacol 1805;11:163–163.
  3. Marchiafava E, Celli A. Sopra i micrococchi della meningite cerebrospinale epidemica. Gazz degli Ospedali 1884;5:59 [Italian]. [Google Scholar].
  4. Flexner S. The results of serum treatment in thirteen hundred cases of epidemic meningitis. J Exp Med 1913;17(5):553–576. DOI: 10.1084/jem.17.5.553.
  5. Neisseria Dankert J. Text book of infectious disease. Cohen J and Powderly, 2nd ed., vol. 2 Philadelphia: Mosby; 2004. pp. 2173–2187.
  6. Manchanda V, Gupta S, Bhalla P. Meningococcal disease: History, epidemiology, pathogenesis, clinical manifestations, diagnosis, antimicrobial susceptibility and prevention. IJMM 2006;24(1):7–19. DOI: 10.4103/0255-0857.19888.
  7. Frash CE, Zollinger WD, Poolman JT. Serotype antigens of Neisseria meningitidis and a proposed scheme for designation of serotypes. Rev Infect Dis 1985;7(4):504–510. DOI: 10.1093/clinids/7.4.504.
  8. Vogel U, Claus H, Frosch M. Rapid serogroup switching in Neisseria. N Engl J Med 2000;324(3):219–220. DOI: 10.1056/NEJM200001203420319.
  9. Swartley JS, Marfin AA, Edupuinganti S, et al. Capsule switching of Neisseria meningitidis. Proc Natl Acad Sci USA 1997;94(1):271–276. DOI: 10.1073/pnas.94.1.271.
  10. Virji M, Saunders JR, Sims G, et al. Pilus-facilitated adherence of Neisseria meningitidis to human epithelial and endothelial cells: Modulation of adherence phenotype occurs concurrently with changes in primary aminoacid sequences and the glycosylation of pilin. Mol Microbiol 1993;10(5):1013–1028. DOI: 10.1111/j.1365-2958.1993.tb00972.x.
  11. Heckels JE. Structure and function of pili of pathogenic Neisseria species. Clin Microbiol Rev 1989;2(Suppl):66–73. DOI: 10.1128/CMR.2.Suppl.S66-S73.1989.
  12. Meyer TF, Pohlner J, Van Putten JPM. Biology of pathogenic Neisseria. Curr Top Microbiol Immune 1994;192:283–317.
  13. Hitchcock PJ. Unified nomenclature for pathogenic Neisseria species. Clin Microbiol Rev 1989;2(Suppl):64–65. DOI: 10.1128/CMR.2.Suppl.S64-S65.1989.
  14. Virji M, Evans D, Hadfield S, et al. Critical determinants of host receptor targeting by Neisseria meningitidis and Neisseria gonorrhoeae: Identification of Opa adhesitopes on the N-domain of CD66 molecules. Mol Microbiol 1999;34(3):538–551. DOI: 10.1046/j.1365-2958.1999.01620.x.
  15. De Vries FP, Cole R, Dankert J, et al. Neisseria meningitis producing Opc afhesion binds epithelial cell proteoglycan receptors. Mol Microbiol 1998;27(6):1203–1212. DOI: 10.1046/j.1365-2958.1998.00763.x.
  16. Swanson J, Bellard RJ, Hill SA. Neisserial surface variation: how and why? Curr Opin Genet Dev 1992;2(5):805–811. DOI: 10.1016/S0959-437X(05)80143-1.
  17. Brandtzaeg P. Systemic meningococcal disease: clinical pictures and patho-physiological background. Rev Med microbial 1996;7:63–72. DOI: 10.1097/00013542-199604000-00001.
  18. Harrison OB, Claus H, Jiang Y, et al. Description and nomenclature of Neisseria meningitides capsule locus. Emerging Infectious Disease 2013;19:4. DOI: 10.3201/eid1904.111799.
  19. Das BK, Agrawal SK. Meningococcal meningitis in northern india- study of an endemic disease. TB of meningococcal meningitis - Recent perspective, ch. 2, Chaudhry Rama, Kotentwork; 2019. pp. 6–20. ISBN: 978-93-83988-13-6.
  20. Schwartz B, Moore PS, Broome CV. Global epidemiology of meningococcal disease. Clin Microbiol Rev 1989;2(Suppl 2):S118–S124. DOI: 10.1128/CMR.2.Suppl.S118-S124.1989.
  21. Brouwer MC, Tunkel AR, Van de Beek D. Epidemiology, diagnosis and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Review 2010;23(3):467–492. DOI: 10.1128/CMR.00070-09.
  22. Steinhoff MC. Global epidemiology of meningococcal infections. TB of Infectious Disease Epidemiology – Theory and practice Nelson KE, Williams CM 2nd ed., Sudbury, Massachussets: Jones and Bartlett; 2007. pp. 637–651.
  23. Meningoccal in meningitis - Australian meningococcal surveillance program.
  24. Lingappa JR, Al-Rabeah AM, Hajjeh R, et al. Serogroup W-135 meningococcal disease during the hajj, 2000. Emerg Infect Dis 2003;9:665–671. DOI: 10.3201/eid0906.020565.
  25. Greenwood B. 100 Years of epidemic meningitis in west Africa- Has anything changed? Trop Med Int Health 2006;11(6):773–780. DOI: 10.1111/j.1365-3156.2006.01639.x.
  26. Lepeyssonnie L. La méningite cérébrospinalé en Afrique. Bull WHO 1963;28(Suppl):53–114.
  27. Hazarika RD. Response to epidemic meningitis in Africa, 1997. Wkly Epidemiol Rec 1997;72(42):313–318.
  28. Health Status Indicators, National Health Profile, 2018, Government of India,
  29. Meningococcal disease: Need to remian alert. CD Alert. Monthly newsletter of teh National Centre for Disease Control, Directorate General of Health Services, Government of India, Oct-Nov 2009; Vol. 13: No. 3.
  30. Orr HJ, Gray SJ, Macdonald M, et al. Saliva and meningococcal transmission. Emerg Infect Dis 2003;9(10):1314–1315. DOI: 10.3201/eid0910.030344.
  31. Nelson JD. Jails, microbes, and the three-foot barrier. NEJM 1996;335(12):885–886. DOI: 10.1056/NEJM199609193351210.
  32. Caugant DA, Hoiby EA, Rosenqvist E, et al. Transmission of Neisseria meningitidis among asymptomatic military recruits and antibody analysis. Epidemiol Infct 1992;109(2):241–253. DOI: 10.1017/S0950268800050196.
  33. van Deuren M, Brandtzaeg P, van der Meer JWM. Update on meningococcal disease with emphasis on pathogenesis and clinical management. Clin Microbiol Rev 2000;13(1):144–166. DOI: 10.1128/CMR.13.1.144.
  34. Stephens DS, Farley MM. Pathogenic events during infection of the human nasopharynx with Neisseria meningitis and Haemophilus influenzae. Rev Infec Dis 1991;13(1):22–23. DOI: 10.1093/clinids/13.1.22.
  35. Hill DJ, Griffiths NJ, Borodina E, et al. Cellular and molecular biology of Neisseria meningitis colonization and invasive disease. Clin Sci 2010;118:547–564. DOI: 10.1042/CS20090513.
  36. Feavers IM, Pizza M. Meningococcal protein antigens and vaccines. Vaccine 2009;27(Suppl 2):B42–B50. DOI: 10.1016/j.vaccine.2009.05.001.
  37. Merz AJ, So M, Sheetz MP. Pilus retraction powers bacterial twitching motility. Nature 2000;407(6800):98–102. DOI: 10.1038/35024105.
  38. Marceau M, Forest K, Beretti JL, et al. Consequences of the loss of O-linked glycosylation of meningococcal type IV pilin on piliation and pilus-mediated adhesion. Mol Microbiol 1998;27(4):705–715. DOI: 10.1046/j.1365-2958.1998.00706.x.
  39. Diaz Romero J, Outschoorn IM. Current status of meningococcal group B vaccine candidates: capular or noncapsular? Clin microbial rev 1994;7(4):559–575. DOI: 10.1128/CMR.7.4.559-575.1994.
  40. Leimkugel J, Hodgson A, Forgor AA, et al. Clonal waves of Neisseria colonisation and disease in the african meningitis belt: eight-year longitudinal study in northern Ghana. PLoS Med 2007;4(3):e101. DOI: 10.1371/journal.pmed.0040101.
  41. Mairey E, Genovesio A, Donnadieu E, et al. Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood-brain barrier. J Exp Med 2006;203(8):1939–1950. DOI: 10.1084/jem.20060482.
  42. Mikaty G, Soyer M, Mairey E, et al. Extracellular bacterial pathogen induces host cell surface reorganization to resist shear stress. PLoS Pathog 2009;5(2):e1000314. DOI: 10.1371/journal.ppat.1000314.
  43. Carbonnelle E, Hill DJ, Morand P, et al. Meningococcal interactions with the host. Vaccine 2009;27(Suppl 2):B78–B89. DOI: 10.1016/j.vaccine.2009.04.069.
  44. Uria MJ, Zhang Q, Li Y, et al. A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies. J Exp Med 2008;205(6):1423–1434. DOI: 10.1084/jem.20072577.
  45. Nassif X, Pujol C, Morand P, et al. Interactions of pathogenic Neisseria with host cells. Is it possible to assemble the puzzle? Mol Microbiol 1999;32(6):1124–1132. DOI: 10.1046/j.1365-2958.1999.01416.x.
  46. Massari P, Ho Y, Wetzler LM. Neisseria meningitidis porin Por b interacts with mitochondria and protects cells from apoptosis. Proc Natl Acad Sci USA 2000;97(16):9070–9075. DOI: 10.1073/pnas.97.16.9070.
  47. Sullivan TD, LaScolea LJ Jr. Neisseria meningitidis bacteremia in children: quantification of bacteremia and spontaneous clinical recovery without antibiotic therapy. Pediatrics 1987;80(1):63–67.
  48. Pathan N, Faust SN, Levin M. Pathophysiology of meningococcal meningitis and septicaemia. Arch Dis Child 2003;88(7):601–607. DOI: 10.1136/adc.88.7.601.
  49. Brandtzaeg P, Kierulf P, Gaustad P, et al. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis 1989;159(2):195–204. DOI: 10.1093/infdis/159.2.195.
  50. Anderson BM. Endotoxin release from Neisseria meningitidis. Relationship between key bacterial characteristics and meningococcal disease. Scand J Infect Dis 1989;64:1–43. DOI: 10.3109/inf.1989.21.suppl-64.01.
  51. Prins JMP, Lauw FN, Derkx BHF, et al. Endotoxin release and cytokine production in acute and chronic meningococcemia. Clin Exp Immunol 1998;114(2):215–219. DOI: 10.1046/j.1365-2249.1998.00715.x.
  52. Lewis LA, Sanjay R. Meningococcal disease and the complement system. Virulence 2014;5(1):1–29. DOI: 10.4161/viru.26515.
  53. Wright SD, Ramos RA, Tobias PS, et al. CD14, a receptor for complexes of lipoppolysaccharide (LPS) and LPS binding protein. Science 1990;249(4975):1431–1433. DOI: 10.1126/science.1698311.
  54. Klein NJ, Shennan GI, Heydermann RS, et al. Alteration in glycosaminoglycan metabolism and surface change on human umbilical vein endothelial cells induced b cytokines, endotoxin and neutrophils. J Cell Sci 1992;102(Pt. 4):821–832.
  55. Oragui EE, Nadel S, Kyd P, et al. Increased excretion of urinary glycosaminoglycans in meningococcal septicaemia and their relationship to proteinuria. Crit Care Med 2000;28(8):3002–3008. DOI: 10.1097/00003246-200008000-00054.
  56. Kornelisse Rf, Hazelzet JA, Salvelkoul HF, et al. The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock. J Infect Dis 1996;173(5):1148–1156. DOI: 10.1093/infdis/173.5.1148.
  57. 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 1999;354(9178):556–560. DOI: 10.1016/S0140-6736(99)02220-5.
  58. Kumar A, Thota V, Dee L, et al. Tumor necrosis factor alpha and interleukin 1 beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med 1996;183(3):949–958. DOI: 10.1084/jem.183.3.949.
  59. Kumar A, Brar R, Wang P, et al. Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility. Am J Physiol 1999;276(1 Pt 2):R265–R276. DOI: 10.1152/ajpregu.1999.276.1.R265.
  60. Thiru Y, Pathan N, Bignall S, et al. A myocardial cytotoxic process is involved in the cardiac dysfunction of meningococcal septic shock. Crit Care Med 2000;28:2979–2983. DOI: 10.1097/00003246-200008000-00049.
  61. Britto J, Nadel S, Habibi P, et al. Gastrointestinal perforation complicating meningococcal disease. Pediatr Infect Dis J 1995;14(5):393–394. DOI: 10.1097/00006454-199505000-00012.
  62. Gedde-Dahl TW, Hoiby EA, Schillinger A, et al. An epidemiological, clinical and microbiological follow-up study of incident meningococcal disease cases in Norway, winter 1981-1982. Material and epidemiology in the menOPP project. NIPP Ann 1983;6(2): 155–168.
  63. Jones DM, Mallard RH. Age incidence of meningococcal infection England and wales, 1984-1991. J Infect 1993;27(1):83–88. DOI: 10.1016/0163-4453(93)93978-D.
  64. Dass Hazarika R, Deka NM, Khriem AB, et al. Invasive meningococcal disease- an analysis of 110 cases from a tertiary care centre in north east india. IJP 2013;80(5):359–364. DOI: 10.1007/s12098-012- 0855-0.
  65. Hodgetts TJ, Brett A, Castle N. The early management of meningococcal disease. J Accid Emerg Med 1998;15(2):72–76. DOI: 10.1136/emj.15.2.72.
  66. Strelow VL, Vidal JE. Invasive meningococcal disease. Arq Neuropsiquiatr 2013;71(9-B):653–658. DOI: 10.1590/0004-282X20130144.
  67. Huang H-R, Chen H-L, Chu S-M. Clinical spectrum of meningococcal infection in infants younger than six months of age. Chang Gung Med J 2006;29(1):107–113.
  68. Meningococcal disease (Neisseria meningitidis) - Case classification, National Notifiable Disease Surveillance System (NNDSS),, Last updated 2015.
  69. Hart CA, Thomson APJ. Meningococcal disease and its management in children. BMJ 2006;333(7570):685–690. DOI: 10.1136/bmj.38968.683958.AE.
  70. Branco RG, Amoretti CF, Tasker RC. Meningococcal disease and meningitis. J Pediatr (Rio J) 2007;83:S46–S53. DOI: 10.2223/ JPED.1612.
  71. Wells LC, Smith JC, Weston VC, et al. The child with a non-blanching rash: how likely is meningococcal disease? Arch Dis Child 2001;85(3):218–222. DOI: 10.1136/adc.85.3.218.
  72. Marzouk O, Thomson APJ, Sills J, et al. Features and outcome in meningococcal disease presenting with maculopapular rash. Arch Dis Child 1991;66(4):485–487. DOI: 10.1136/adc.66. 4.485.
  73. Pollard AJ, Britto J, Nadel S, et al. Emergency management of meningococcal disease. Arch Dis Child 1999;80(3):290–296. DOI: 10.1136/adc.80.3.290.
  74. Riordan FAI, Thompson APJ, Sills JA, et al. Prospective study of door to needle time in meningococcal disease. J Accid Emerg Med 1998;15(4):249–251. DOI: 10.1136/emj.15.4.249.
  75. Visintin C, Mugglestone MA, Fields EJ, et al. Management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of NICE guidance. BMJ 2010;340(c3209):c3209. DOI: 10.1136/bmj.c3209.
  76. Mortensen JE, Gerrety MJ, Gray LD. Surveillance of antimicrobial resistance in Neisseria meningitidis from patients in the Cincinnati tristate region (Ohio, Kentucky, and Indiana). J Clin Microbiol 2006;44(4):1592–1593. DOI: 10.1128/JCM.44.4.1592-1593.2006.
  77. Vázquez JA, Enriquez R, Abad R, et al. Antibiotic resistant meningococci in Europe: any need to act? FEMS Microbiol Rev 2007;31(1):64–70. DOI: 10.1111/j.1574-6976.2006.00049.x.
  78. Manchanda V, Bhalla P. Emergence of non-ceftriaxone-susceptible Neisseria meningitidis in india. J Clin Microbiol 2006;44(11): 4290–4291. DOI: 10.1128/JCM.01903-06.
  79. Singhal S, Purnapatre KP, Kalia V, et al. Ciprofloxacin-resistant Neisseria meningitidis, Delhi, india. Emerg Infect Dis 2007;13(10):1614–1616. DOI: 10.3201/eid1310.060820.
  80. Tunkel AR, van de Beek D, Scheld WM. Acute meningitis. Mandell, Douglas, and Bennett's Priciples and Practice of Infectious Diseases, 7th ed., Churchill Livingstone, Elsevier; 2010. pp. 1189–1229.
  81. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia and Neisseria meningitidis. Lancet 2007;369(9580):2196–2210. DOI: 10.1016/S0140-6736(07) 61016-2.
  82. DeKleijn ED, Joosten KF, Van Rijn B, et al. Low serum cortisol in combination with high adrenocorticotrophic hormone concentrations are associated with poor outcome in children with severe meningococcal disease. Pediatr Infect Dis J 2002;21(4): 330–336. DOI: 10.1097/00006454-200204000-00013.
  83. Takac I, Kvolik S, Divkovic D, et al. Conservative surgical management of necrotic tissues following meningococcal sepsis: case report of a child treated with hyperbaric oxygen. Undersea Hyperb Med 2010;37(2):95–99.
  84. Dass R, Barman H, Duwarah SG, et al. Immune complex reaction after successful treatment of meningococcal disease: an excellent response to IVIG. Rheumatol Int 2013;33(1):231–233. DOI: 10.1007/s00296-010-1555-6.
  85. Stiehm RE, Damrosch DS. Factors in the prognosis of meningococcal infection. Med Prog 1966;68(3):457–467.
  86. Thomson AP, Sills JA, Hart CA. Validation of Glasgow meningococcal septicaemia prognostic score: a 10 year retrospective study. Crit Care Med 1991;19(1):26–30. DOI: 10.1097/00003246-199101000 -00010.
  87. Naeini AE. Importance of scoring systems in prognosticating meningococcaemia. J Res Med Sciences 2005;1:34–37.
  88. Bilukha OO, Rosenstein N. National center for infectious diseases CDC, prevention. Prevention and control of meningococcal disease. Recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2005;54(RR-7):1–21.
  89. Antimicrobial prophylaxis- Meningococcal meningitis. Meningitis- prevention of secondary cases of meningococcal meningitis/septicaemia. East Kent Hospital University, NHS Foundation Trust.
  90. Cohn AC, MacNeil JR, Clark TA, et al. Prevention and control of meningococcal disease: recommendations of the advisory committee on immunization Practices (ACIP). MMWR 2013;62(RR02):1–22.
  91. Balasubramanium S, Shah A, Pemde HK, et al. Indian academy of pediatrics (IAP) advisory committee on vaccines and immunization Practices (ACVIP) recommended immunization schedule (2018-2019) and update on immunization for children aged 0 through 18 years. Indian Peds 2018;55:1066–1074. DOI: 10.1007/s13312-018- 1444-8.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.