Meningococcal meningitis

Introduction
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By Douglas J Lanska MD MS MSPH

Dr. Douglas Lanska, staff neurologist at the VA Medical Center in Tomah, Wisconsin, explains the clinical presentation, pathophysiology, diagnostic workup, and management of meningococcal meningitis. Meningococcal meningitis may be indistinguishable from other bacterial meningitides, although the classic triad of fever, neck stiffness, and change in mental status is significantly less common in patients with meningococcal meningitis (27%) than in patients with pneumococcal meningitis (58%). Although less than one third of affected patients present with the classic triad of fever, nuchal rigidity, and change in mental status, nearly 90% have at least 2 of the following 4 signs on presentation: fever, nuchal rigidity, change in mental status, and rash. The most recent recommendations from the United Kingdom's National Institute for Health and Clinical Excellence on the management of bacterial meningitis and meningococcal septicemia in children and young people under 16 years of age are included, as well as the 2010 updated recommendations for use of meningococcal conjugate vaccines from the U.S. Advisory Committee on Immunization Practices.

Key Points

  • Meningococcemia presents abruptly with fever, chills, nausea, vomiting, headache, myalgias, malaise, prostration, and rash. Rash is somewhat variable and may be urticarial, maculopapular, or petechial.
  • Acute fulminating cases of meningococcal septicemia (Waterhouse-Friderichsen syndrome) occur mainly in children younger than 10 years of age and are characterized by vomiting, diarrhea, extensive purpura, disseminated intravascular coagulation, cyanosis, convulsions, shock, coma, and often death within hours despite appropriate treatment; many of these cases have meningitis and adrenal insufficiency with hemorrhage into the adrenal glands or adrenal infarction.
  • Meningococcal meningitis may be indistinguishable from other bacterial meningitides, although the classic triad of fever, neck stiffness, and change in mental status is significantly less common in patients with meningococcal meningitis (27%) than in patients with pneumococcal meningitis (58%).
  • Although less than one third of affected patients present with the classic triad of fever, nuchal rigidity, and change in mental status, nearly 90% have at least 2 of the following 4 signs on presentation: fever, nuchal rigidity, change in mental status, and rash.
  • Neisseria meningitidis is an aerobic gram-negative diplococcus. The strains most commonly implicated in systemic disease are A, B, C, W-135, and Y. In the United States, groups B, C, and Y are the most common serogroups implicated, and each account for about 30% of reported cases.
  • North American outbreaks (as opposed to isolated cases) are confined primarily to serogroup C (less commonly to Y and W-135), although the frequency of serogroup Y outbreaks increased markedly during the 1990s.
  • Although rates of disease are highest among children less than 2 years of age, almost two thirds of meningococcal disease in the United States occurs in those older than 10 years. The vast majority of cases (95% to 98%) are sporadic. However, outbreaks of meningococcal disease have been occurring with increasing frequency in the United States.
  • Meningococcal disease outbreaks are particularly likely to occur in semiclosed communities, such as day care centers, schools, colleges, nursing homes, and military recruit camps.
  • Almost all secondary cases in an outbreak occur within 8 days of the index case.
  • The U.S. Centers for Disease Control and Prevention recommends routine vaccination with quadrivalent meningococcal conjugate vaccine of adolescents 11 to 18 years of age and vaccination of persons 2 to 55 years of age who have an increased risk of invasive meningococcal disease.
  • A quadrivalent meningococcal polysaccharide vaccine that is effective against meningococci in groups A, C, Y, and W-135 (Menomune-A/C/Y/W-135 or MPSV4) is licensed in the United States for adults and for children 2 years of age and older.
  • Meningococcal conjugate vaccines (ie, in which meningococcal polysaccharides have been conjugated to carrier proteins) were recently licensed in the United States and other countries. Conjugate vaccines are immunogenic, can induce high concentrations of bactericidal antibodies, induce immunologic memory, reduce colonization, and provide herd immunity to the general population.
  • Two quadrivalent meningococcal conjugate vaccines that are effective against meningococci in groups A, C, Y, and W-135 (Menactra or MCV4 and Menveo or MenACWY-CRM) are licensed in the United States. MCV4 (Menactra) is licensed in the U.S. for individuals aged 2 to 55 years, whereas MenACWY-CRM (Menveo) is licensed for individuals aged 11 to 55 years.
  • No vaccine is available in the United States for prevention of group B meningococcal disease, because the serogroup B capsular polysaccharide is poorly immunogenic in humans.
  • No vaccine is presently licensed in the United States for prevention of meningococcal disease in children younger than 2 years of age, even though this group has the highest rate of invasive meningococcal disease.
  • The case-fatality ratio for meningococcal disease is approximately 10%, and 11% to 26% of survivors have serious sequelae, including neurologic disability (eg, focal neurologic deficits, seizures, etc.), limb loss, and deafness.
  • Because of the risks of severe morbidity and death, appropriate antibiotic therapy should be rapidly initiated in patients suspected of having meningococcal disease. Prior to confirmation of meningococcal disease as the cause of the illness, empiric antibiotic coverage should be given directed at the most likely pathogens based on epidemiologic considerations (eg, age, geographic location, etc.) and the known prevalence of antibiotic resistance for these organisms. No investigations should delay initiating antibiotic therapy once the diagnosis of meningococcal meningitis is suspected.
  • Children who have suspected bacterial meningitis or meningococcal disease should be immediately treated with intravenous ceftriaxone, with the addition of amoxicillin or ampicillin for children younger than 3 months, and the addition of vancomycin for those who have recently travelled outside of the country or who have had prolonged or multiple exposures to antibiotics.
  • Recommendations for initial empiric antimicrobial therapy in adults with community-acquired bacterial meningitis are vancomycin plus a third-generation cephalosporin (eg, cefotaxime or ceftriaxone) for those aged 16 to 50 years and vancomycin plus a third-generation cephalosporin plus ampicillin for those older than 50 years, or for those with alcoholism or altered immune status. Generally, combination therapy should be continued until results of in-vitro susceptibility testing are available.