Meningococcemia 

  • Author: Mahmud H Javid, MBBS; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Oct 26, 2011
 

Background

Meningococcemia is caused by Neisseria meningitidis, an encapsulated gram-negative diplococcus as depicted in the image below. Acquisition of N meningitidis can result in asymptomatic pharyngeal colonization or invasive disease. There are at least 13 serogroups, with the most important being serogroups A, B, C, and W-135. Meningococcemia is defined as dissemination of meningococci into the bloodstream and is a medical emergency, making early recognition of the disease essential.

Gram-negative intracellular diplococci. Courtesy PGram-negative intracellular diplococci. Courtesy Professor Chien Liu.

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.

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Pathophysiology

Humans are the only known reservoir of N meningitis 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, such as the type IV pilus encoded by pilC, which binds to human cell surface protein CD46. 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 of an epidemic strain can reach 90%. 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,[2] as follows:

  • A polysaccharide capsule (which also determines the serogroup) enables the organism to resist phagocytosis.[3]
  • 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.[4]
  • 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.

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Epidemiology

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.[5]

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.[6, 7] 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.

Meningococcal disease may be a significant but under-reported problem in developing Asian countries.[8]

Serogroup W-135 has been associated with pilgrims returning from the hajj.[6, 9]

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.[10]
  • 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.[11]
  • Occult meningococcemia is an uncommon form of infection that affects children aged 3-24 months.
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Contributor Information and Disclosures
Author

Mahmud H Javid, MBBS  Consultant, Infectious Diseases, Shifa International Hospital, Islamabad, Pakistan

Mahmud H Javid, MBBS 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, AAHIVS  Associate Professor of Clinical Medicine, The School of Medicine at Stony Brook University Medical Center; Adjunct Clinical Associate Professor, Department of Medicine, New York College of Osteopathic Medicine of New York Institute of Technology; Attending Physician, Department of Medicine, Division of Infectious Diseases, Director of HIV Prevention Services, Administrative HIV Designee, Nassau University Medical Center

Shadab Hussain Ahmed, MD, FACP, FIDSA, AAHIVS is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, and International AIDS Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary D Nettleman, MD, MS, MACP  Professor and Chair, Department of Medicine, Michigan State University College of Human Medicine

Mary D Nettleman, MD, MS, MACP is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Aaron Glatt, MD  Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, St Joseph Hospital (formerly 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.

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.

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Dorsum of the hand showing a petechial rash. Courtesy of Professor Chien Liu.
Petechial lesions on the palm. Courtesy of Professor Chien Liu.
Petechial rash on lower extremities. Courtesy of Professor Chien Liu.
Conjunctival petechiae. Courtesy of Professor Chien Liu.
Gram-negative intracellular diplococci. Courtesy Professor Chien Liu.
 
 
 
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