eMedicine Specialties > Infectious Diseases > Bacterial Infections

Meningococcemia

Author: Mahmud H Javid, MD, Chief, Section of Infectious Diseases, Shifa Hospital, Islamabad, Pakistan
Coauthor(s): Shadab Hussain Ahmed, MD, FACP, FIDSA, MACGS, AAHIVS, Associate Professor of Clinical Medicine, State University of New York at Stony Brook; Attending Physician, Division of Infectious Diseases, Director of HIV Prevention Services, Nassau University Medical Center
Contributor Information and Disclosures

Updated: Feb 24, 2009

Introduction

Background

Meningococcemia is caused by Neisseria meningitidis, an encapsulated gram-negative diplococcus. Acquisition of N meningitidis can result in asymptomatic pharyngeal colonization or invasive disease. Meningococcemia is defined as dissemination of meningococci into the bloodstream and is a medical emergency, making early recognition of the disease essential.

Patients with acute meningococcal infection can present clinically with one of 3 syndromes: meningitis, meningitis with meningococcemia, or meningococcemia without obvious meningitis. Prior to the advent of antibiotics, almost all cases resulted in death or marked morbidity.

Pathophysiology

Humans are the only natural reservoir of meningococci and can transmit the organisms by aerosols or nasopharyngeal secretions. Meningococcal infection is preceded by nasopharyngeal colonization. Attachment to the nasopharyngeal epithelial cells is aided by meningococci-expressed pili, which bind to human cell surface protein CD 46. Meningococci then enter the bloodstream and spread to specific sites, such as the meninges or joints, or disseminate throughout the body. Five percent of individuals become long-term carriers, most of whom are asymptomatic. In outbreaks, the carriage rate can be as high as 35%. Intimate contacts of individuals with meningococcemia are 100-1000 times more likely than normal to acquire infection.

A study of 14,000 teenagers in the United Kingdom found that attendance at pubs or clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with an increased risk of meningococcal carriage.1

Meningococci have 3 important virulence factors, as follows:

  • A polysaccharide capsule enables the organism to resist phagocytosis.
  • A lipo-oligosaccharide endotoxin (LOS) can be shed in large amounts by a process called blebbing, causing fever, shock, and other pathophysiology. This is considered the principal factor that produces the high endotoxin levels in meningococcal sepsis. Meningococcal LOS interacts with human cells, producing proinflammatory cytokines and chemokines, including interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). LOS is one of the important structures that mediate meningococcal attachment to and invasion into epithelial cells.2
  • An immunoglobulin A1 protease cleaves lysosomal membrane glycoprotein-1 (LAMP1), helping the organism to survive intracellularly.

Individuals with immunity against meningococcal infections have bactericidal antibodies against cell wall antigens and capsular polysaccharide. A deficiency of circulating antimeningococcal antibodies is associated with disease.

Impairment of the protein C anticoagulation pathway leads to the development of purpura fulminans in meningococcemia.

Endotoxin, cytokines, and free radicals damage the vascular endothelium, producing platelet deposition and vasculitis.

Frequency

United States

The incidence of meningococcal disease in the United States is estimated to be 0.7-1.4 cases per 100,000 population. The case-fatality rate is approximately 10%. The incidence and case fatality rates have been relatively constant. While serogroups B and C are most common, an increase in serogroup Y disease was noted in the 1990s.

An outbreak of meningococcal disease is defined as 3 or more cases in a 3-month period or a primary attack rate of at least 10 cases per 100,000 population.

International

Serogroups A, B, and C account for most cases worldwide. Serogroups A and C predominate in Asia and Africa, and serogroups B and C predominate in Europe, North America, and South America.

In the United Kingdom, the number of cases of meningococcal disease and attributed deaths rose in 1995, due mainly to serogroup C disease. This declined when serogroup C conjugate vaccine was introduced in the national immunization program.3

For more than a century, serogroup A meningococcal disease has been endemic in the African Meningitis Belt, which extends from Ethiopia in eastern Africa to Senegal in West Africa.

Outbreaks of meningococcal disease occurred during the annual hajj (pilgrimage) in Saudi Arabia in 2000 and 2001 among pilgrims and household contacts.4,5 Outbreaks have also occurred in Africa, parts of Asia, South America, and the former Soviet republics. Serogroup A is usually implicated in these epidemics. Outbreaks are also occasionally reported in the United States.

Up to 95% of patients with meningococcal disease have meningococcemia and/or meningitis. Up to 50% have meningococcemia without meningitis. Fulminant meningococcemia occurs in up to 20%. Nosocomial transmission to patient care personnel and laboratory staff is rare.

Mortality/Morbidity

  • The mortality rate of fulminant infection remains high, with most deaths occurring within 48 hours.
  • Half of all patients with shock who die do so within the first 12 hours of hospitalization.6
  • In industrialized countries, the mortality rate can exceed 40%; in developing countries, it is higher and can approach 70%.

Race

In the United States, the incidence of meningococcal disease is higher in blacks and in lower socioeconomic groups.

Sex

Meningococcal disease is somewhat more prevalent in males (1.2 cases per 100,000) than in females (1 case per 100,000).

Age

  • In epidemics of meningococcal disease, people of any age may be affected, with the case distribution shifted toward older individuals.
  • Endemic meningococcal disease is most common in children aged 6-36 months. Children younger than 6 months are protected by maternal antibodies. In New York City, from 1989-2000, the overall incidence rates of meningococcal disease decreased. This was more evident in the younger age groups, and this increased the median age of patients from 15 years in 1989-1991 to 30 years in 1998-2000.7
  • Occult meningococcemia is an uncommon form of infection that affects children aged 3-24 months.

Clinical

History

Persons with meningococcal disease may present with a nonspecific prodrome of cough, headache, and sore throat. This is followed by rapid onset of fever with chills, arthralgias, and myalgias. The potential rapidity of progression cannot be stressed enough.

  • In fulminant meningococcemia, collapse occurs within a few hours, with rapid enlargement of petechiae and purpuric lesions.
  • Meningitis that accompanies meningococcemia may result in headache, neck stiffness, lethargy, and drowsiness.
  • Decreased mentation and coma may be present.
  • Young children may present with sudden onset of fever and lethargy. They may also have vomiting and convulsions.
  • In chronic meningococcemia (rare), painful skin lesions are present on the extremities, similar to those seen in gonococcemia, with migratory polyarthritis and tenosynovitis. Antibiotic treatment results in a prompt response.

Physical

Patients with meningococcal disease appear severely ill.

  • Tachycardia and mild hypotension are present.
  • Fever is moderate. High fever is present in fulminant meningococcemia.
  • A petechial rash develops in 50-80% of patients and involves the axillae, flanks, wrists, and ankles. Petechiae are often located in the center of lighter-colored macules. Lesions commonly begin on the trunk and legs in areas where pressure is applied. They are discrete lesions 1-2 mm in diameter. Confluence of lesions results in hemorrhagic patches, often with central necrosis.
  • In some cases, a transient maculopapular rash develops, usually lasting for less than 48 hours.8
  • Congestive heart failure, gallops, and pulmonary edema may be present. Other evidence of end-organ damage may also rapidly appear.
  • Patients with fulminant meningococcemia rapidly deteriorate clinically, with hypotension and respiratory failure.
  • Pericarditis can occur during the acute disease or in the recovery period and is associated with serogroup C disease.

Causes

Meningococci (0.6 µm X 0.8 µm) are gram-negative single cocci or diplococci with flattened adjacent sides. Older cultures can vary considerably in size and shape. Serotyping is based on the polysaccharide capsule. The organisms grow at 35-37°C in a moist oxygen-reduced atmosphere containing 5-19% carbon dioxide on media that contains blood.

  • Seroagglutination is used to segregate meningococci into 13 serogroups: A, B, C, D, X, Y, Z, E, W-135, H, I, K, and L. Ninety-eight percent of infections are caused by encapsulated serogroups A, B, C, Y, and W-135.
  • Individuals with complement component deficiencies are at an increased risk for meningococcal infections.
  • Recurrent meningococcemia has also been reported in patients with immunoglobulin G2 subclass deficiency.

More on Meningococcemia

Overview: Meningococcemia
Differential Diagnoses & Workup: Meningococcemia
Treatment & Medication: Meningococcemia
Follow-up: Meningococcemia
Multimedia: Meningococcemia
References
[ CLOSE WINDOW ]

References

  1. 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].

  2. 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].

  3. 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].

  4. 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].

  5. 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].

  6. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. Jun 30 2007;369(9580):2196-210. [Medline].

  7. 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].

  8. Feldman HA. Meningococcal infections. Adv Intern Med. 1972;18:117-40. [Medline].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

  13. Barquet N, Domingo P, Cayla JA. Oral Antibiotics and Outcome in Meningococcemia. Arch Intern Med. Jul 24 2000;160(14):2220-2223. [Medline].

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. Drapkin MS, Wisch JS, Gelfand JA, et al. Plasmapheresis for fulminant meningococcemia. Pediatr Infect Dis J. Jun 1989;8(6):399-400. [Medline].

  19. 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].

  20. 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].

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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].

  26. Hyszczak R, Bartold KP, Eggleston D. Gangrene associated with meningococcemia. AJR Am J Roentgenol. Jul 1988;151(1):203-4. [Medline].

  27. 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].

  28. 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].

  29. Marotto MS, Marotto PC, Sztajnbok J, Seguro AC. Outcome of acute renal failure in meningococcemia. Ren Fail. Nov 1997;19(6):807-10. [Medline].

  30. 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].

  31. 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].

  32. 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].

  33. 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].

  34. 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].

  35. Riedo FX, Plikaytis BD, Broome CV. Epidemiology and prevention of meningococcal disease. Pediatr Infect Dis J. Aug 1995;14(8):643-57. [Medline].

  36. Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal disease. N Engl J Med. May 3 2001;344(18):1378-88. [Medline].

  37. Salzman MB, Rubin LG. Meningococcemia. Infect Dis Clin North Am. Dec 1996;10(4):709-25. [Medline].

  38. 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].

  39. Schlossberg D. Fever and rash. Infect Dis Clin North Am. Mar 1996;10(1):101-10. [Medline].

  40. Singh J, Arrieta AC. Management of meningococcemia. Indian J Pediatr. Oct 2004;71(10):909-13. [Medline].

  41. 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].

  42. 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].

  43. 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].

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

  45. 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].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

meningococcemia, Waterhouse-Friderichsen syndrome, Neisseria meningitidis infection, N meningitidis, meningitis with meningococcemia, acute meningococcal infection, meningitis, meningococci, fulminant meningococcemia, meningococci A, meningococci B, meningococci C, meningococci Y, meningococci W-135, immunoglobulin G2 subclass deficiency, purpura fulminans, meningococcal disease, occult meningococcemia, chronic meningococcemia, meningococcal sepsis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Mahmud H Javid, MD, Chief, Section of Infectious Diseases, Shifa Hospital, Islamabad, Pakistan
Mahmud H Javid, MD is a member of the following medical societies: Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Shadab Hussain Ahmed, MD, FACP, FIDSA, MACGS, AAHIVS, Associate Professor of Clinical Medicine, State University of New York at Stony Brook; Attending Physician, Division of Infectious Diseases, Director of HIV Prevention Services, Nassau University Medical Center
Shadab Hussain Ahmed, MD, FACP, FIDSA, MACGS, AAHIVS is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and International AIDS Society
Disclosure: Nothing to disclose.

Medical Editor

Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University
Mary Nettleman, MD, MS is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, New Island Hospital
Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.