Update on meningococcal disease with emphasis on pathogenesis and clinicalmanagement

The only natural reservoir of Neisseria meningitidis is the human nasophary ngeal mucosa,Depending on age, climate, country, socioeconomic status, and other factors, approximately 10% of the human population harbors meningococ ci in the nose. However invasive disease is relatively rare, as it occurs o nly when the following conditions are fulfilled: (i) contact with a virulen t strain, (ii) colonization by that strain, (iii) penetration of the bacter ium through the mucosa, and (iv) survival and eventually outgrowth of the m eningococcus in the bloodstream. When the meningococcus has reached the blo odstream and specific antibodies are absent, as is the case for young child ren or after introduction of a new strain in a population, the ultimate out growth depends on the efficacy of the innate immune response. Massive outgr owth leads within 12 h to fulminant meningococcal sepsis (FMS), characteriz ed by high intravascular concentrations of endotoxin that set free high con centrations of proinflammatory mediators. These mediators belonging to the complement system, the contact system, the Fibrinolytic system, and the cyt okine system induce shock and diffuse intravascular coagulation. FMS can be fatal within 24 h, often before signs of meningitis have developed. In spi te of the increasing possibilities for treatment in intensive care units, t he mortality rate of FMS is still 30%. When the outgrowth of meningococci i n the bloodstream is impeded, seeding of bacteria in the subarachnoidal com partment may lead to overt meningitis within 24 to 36 h. With appropriate a ntibiotics and good clinical surveillance the mortality rate of this form o f invasive disease is 1 to 2%. The overall mortality rate of meningococcal disease can only be reduced when patients without meningitis, i.e., those w ho may develop FMS, are recognized early. This means that the fundamental n ature of the disease as a meningococcus septicemia deserves more attention.