33-12: Meningococcal Meningitis

Meningococcal meningitis is caused by Neisseria meningitidis of groups A, B, C, Y, and W-135, among others. Meningitis due to serogroup A is uncommon in the United States. Serogroup B generally causes sporadic cases. Serogroup C meningococcus is the most common cause of epidemic disease in the United States. Up to 40% of persons are nasopharyngeal carriers of meningococci, but disease develops in relatively few of these persons. Infection is transmitted by droplets. The clinical illness may take the form of meningococcemia (a fulminant form of septicemia without meningitis), meningococcemia with meningitis, or meningitis. Recurrent meningococcemia with fever, rash, and arthritis is seen rarely in patients with certain terminal complement deficiencies. Asplenic patients are also at risk.

A. Symptoms and Signs

High fever, chills, nausea, vomiting, and headache as well as back, abdominal, and extremity pains are typical. Rapidly developing confusion, delirium, seizures, and coma occur in some. On examination, nuchal and back rigidity are typical. Positive Kernig and Brudzinski signs (Kernig sign is pain in the hamstrings upon extension of the knee with the hip at 90-degree flexion; Brudzinski sign is flexion of the knee in response to flexion of the neck) are specific but not sensitive findings. A petechial rash appearing in the lower extremities and at pressure points is found in most cases. Petechiae may vary in size from pinpoint lesions to large ecchymoses or even skin gangrene that may later slough.

B. Laboratory Findings

Lumbar puncture typically reveals a cloudy or purulent cerebrospinal fluid, with elevated pressure, increased protein, and decreased glucose content. The fluid usually contains greater than 1000 cells/mcL, with polymorphonuclear cells predominating and containing gram-negative intracellular diplococci. The absence of organisms in a Gram-stained smear of the cerebrospinal fluid sediment does not rule out the diagnosis. The capsular polysaccharide can be demonstrated in cerebrospinal fluid or urine by latex agglutination; this is useful in partially treated patients, though sensitivity is 60–80%. The organism is usually demonstrated by smear and culture of the cerebrospinal fluid, oropharynx, blood, or aspirated petechiae.

Disseminated intravascular coagulation is an important complication of meningococcal infection and is typically present in toxic patients with ecchymotic skin lesions.

Meningococcal meningitis must be differentiated from other meningitides. In small infants and in older adults, fever or stiff neck is often missing, and altered mental status may dominate the picture.

Rickettsial, echovirus, and, rarely, other bacterial infections (eg, staphylococcal infections, scarlet fever) also cause petechial rash.

Four meningococcal vaccines are available. There are two vaccines with coverage against meningococcal serogroups A, C, Y, and W-135 and two with coverage against meningococcal serogroup B. The two vaccines effective for meningococcal serogroups A, C, Y, and W-135 are the meningococcal polysaccharide vaccine (MPSV4), indicated for vaccination of persons over age 55, and the conjugate vaccine (MCV4), indicated for persons aged 2–55 years. The two vaccines against meningococcal serogroup B are MenB-FHbp and MenB-4C; they are approved for persons aged 10–25 years and are not interchangeable.

The Advisory Committee on Immunization Practices recommends immunization with a dose of MCV4 for preadolescents aged 11–12 with a booster at age 16 (see www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html). For ease of program implementation, persons aged 21 years or younger should have documentation of receipt of a dose of MCV4 not more than 5 years before enrollment to college. If the primary dose was administered before the sixteenth birthday, a booster dose should be administered before enrollment. Vaccine is also recommended as a two-dose primary series administered 2 months apart for persons aged 2 through 54 years with persistent complement deficiency, persons with functional or anatomic asplenia, and for adolescents with HIV infection. All other persons at increased risk for meningococcal disease (eg, military recruits, microbiologists routinely exposed to isolates of N meningitidis, or travelers to an epidemic or highly endemic country) should receive a single dose. One of the meningococcal serogroup B vaccines may be administered to persons 10 years of age or older who are at increased risk for meningococcal disease. These persons include those with persistent complement deficiencies; persons with anatomic or functional asplenia; microbiologists; and persons identified to be at increased risk because of a serogroup B meningococcal disease outbreak. Vaccination of persons aged 16–23 years may provide short-term protection against most strains of serogroup B meningococcal disease.

Eliminating nasopharyngeal carriage of meningococci is an effective prevention strategy in closed populations and to prevent secondary cases in household or otherwise close contacts. Rifampin, 600 mg orally twice a day for 2 days, ciprofloxacin, 500 mg orally once, or one intramuscular 250-mg dose of ceftriaxone is effective. Cases of fluoroquinolone-resistant meningococcal infections have been identified in the United States. However, ciprofloxacin remains a recommended empiric agent for eradication of nasopharyngeal carriage. School and work contacts ordinarily need not be treated. Hospital contacts receive therapy only if intense exposure has occurred (eg, mouth-to-mouth resuscitation). Accidentally discovered carriers without known close contact with meningococcal disease do not require prophylactic antimicrobials.

Blood cultures must be obtained and intravenous antimicrobial therapy started immediately. This may be done prior to lumbar puncture in patients in whom the diagnosis is not straightforward and for those in whom MR or CT imaging is indicated to exclude mass lesions. Aqueous penicillin G is the antibiotic of choice (24 million units/24 h intravenously in divided doses every 4 hours). The prevalence of strains of N meningitidis with intermediate resistance to penicillin in vitro (MICs 0.1–1 mcg/mL) is increasing, particularly in Europe. At what level of resistance penicillin treatment failure can occur is not known. Penicillin-intermediate strains thus far remain fully susceptible to ceftriaxone and other third-generation cephalosporins used to treat meningitis, and these should be effective alternatives to penicillin. In penicillin-allergic patients or those in whom Haemophilus influenzae or gram-negative meningitis is a consideration, ceftriaxone, 2 g intravenously every 12 hours, should be used. Treatment should be continued in full doses by the intravenous route until the patient is afebrile for 5 days. Shorter courses—as few as 4 days if ceftriaxone is used—are also effective.

All patients with suspected meningococcal infection including meningitis and meningococcemia should be admitted for evaluation and empiric intravenous antibiotic therapy.