Meningo Coccal Disease : Clinical Aspects

MENINGO COCCAL  DISEASE :  CLINICAL  ASPECTS

MANIFESTATIONS

The most frequent form of meningococcal infection is acute purulent meningitis, with clini-cal and laboratory features similar to those of meningitis from other causes . A prominent feature of meningococcal meningitis is the appearance of scattered skin pe-techiae, which may evolve into ecchymoses or a diffuse petechial rash. These cutaneous manifestations are signs of the disseminated intravascular coagulation (DIC) syndrome that is part of the endotoxic shock brought on by meningococcal bacteremia (meningococcemia). Meningococcemia sometimes occurs without meningitis and may progress to fulminant DIC and shock with bilateral hemorrhagic destruction of the adrenal glands (Waterhouse – Friderichsen syndrome). However, the disease is not always fulminant, and some patients have only low-grade fever, arthritis, and skin lesions that develop slowly over a period of days to weeks. Meningococci are a rare cause of other infections such as pneumonia, but it is striking that localized infections are almost never recognized in advance of systemic disease.

DIAGNOSIS

Direct Gram smears of cerebrospinal fluid (CSF) in meningitis usually demonstrate the typical bean-shaped, Gram-negative diplococci. Definitive diagnosis is by culture of CSF, blood, or skin lesions. Although N. meningitidis is reputed to be somewhat fragile, it re-quires no special handling for isolation from presumptively sterile sites such as blood and CSF. Growth is good on blood or chocolate agar after 18 hours of incubation. Speciation is based on carbohydrate degradation patterns or immunologic tests. Serogrouping may be performed by slide agglutination methods but has no immediate clinical importance.

TREATMENT

Penicillin is the treatment of choice for meningococcal infections because of its antimeningo-coccal activity and good CSF penetration. Resistance mediated by both -lactamase and altered penicillin-binding proteins (PBPs) has been reported but is still extremely rare. Third-generation cephalosporins such as cefotaxime are effective alternatives to penicillin.

PREVENTION

Until the development and spread of sulfonamide resistance in the 1960s, chemoprophylaxis with these agents was the primary means of preventing spread of meningococcal infections. Rifampin is now the primary chemoprophylactic agent, but ciprofloxacin has also been effec-tive. Penicillin is not effective, probably because of inadequate penetration of the uninflamed nasopharyngeal mucosa. Selection of cases to receive prophylaxis is based on epidemiologic assessment. Risk is highest for siblings of the index case and declines with increasing age and less close contact. For example, an infant sibling sharing the same room as an affected individual would be at the highest risk. Typically, family members are given prophylaxis, but other adults are not. Common-sense exceptions, such as playmates and healthcare workers with very close contact (eg, mouth-to-mouth resuscitation), are made at the discretion of the physician. The presence or absence of nasopharyngeal carriage of N. meningitidisplays no role in this decision, because it does not accurately predict risk of disease.

Purified polysaccharide meningococcal vaccines have been shown to prevent group A and C disease in military and civilian populations, and a quadrivalent vaccine containing A, C, Y, and W-135 polysaccharides is now licensed for use in the United States. Meningo-coccal vaccines are currently used to control epidemics in populations at particular risk such as in military recruits and in those with unique predisposing factors such as comple-ment deficiencies or asplenia. Routine immunization of children is not recommended.

This reluctance for widespread use of meningococcal polysaccharide vaccines is ironic, because it was their development that led to the success of other vaccines made from capsular polysaccharides (see Additional Reading). Like other pure polysaccharides, these vaccines are ineffective in young children, because they stimulate immune re-sponses that are underdeveloped in the first year of life (see Immunity).

With H. influenzae and now Streptococcus pneumoniae, this problem has been over-come by the development of polysaccharide – protein conjugate vaccines, which stimulate T cell – dependent responses . The protein conjugate approach, which is under investigation with N. meningitidis, faces a difficulty not shared by these other two pathogens — the failure of the group B polysaccharide to be immunogenic at all. If this is due to its similarity to human brain antigens, as suspected, it may not be overcome simply by protein conjugation. Group B causes one third of all disease, so no vaccine that omits it is likely to be completely successful. For this reason, other approaches such as the use of OMPs (eg, PorA) are being pursued. Genetically engineered vaccines based on the se-quence of the entire group B meningococcal genome hold the promise of defining proteins that would immunize against all serogroups of N. meningitidis.