title: Classification and pathogenesis of meningococcal infections.
abstract: The clinical symptoms induced by Neisseria meningitidis reflect compartmentalized intravascular and intracranial bacterial growth and inflammation. In this chapter, we describe a classification system for meningococcal disease based on the nature of the clinical symptoms. Meningococci invade the subarachnoid space and cause meningitis in as many as 50-70% of patients. The bacteremic phase is moderate in patients with meningitis and mild systemic meningococcemia but graded high in patients with septic shock. Three landmark studies using this classification system and comprising 862 patients showed that 37-49% developed meningitis without shock, 10-18% shock without meningitis, 7-12% shock and meningitis, and 18-33% had mild meningococcemia without shock or meningitis. N. meningitidis lipopolysaccharide (LPS) is the principal trigger of the innate immune system via activation of the Toll-like receptor 4-MD2 cell surface receptor complex on myeloid and nonmyeloid human cells. The intracellular signals are conveyed via MyD88-dependent and -independent pathways altering the expression of >4,600 genes in target cells such as monocytes. However, non-LPS molecules contribute to inflammation, but 10-100-fold higher concentrations are required to reach the same responses as induced by LPS. Activation of the complement and coagulation systems is related to the bacterial load in the circulation and contributes to the development of shock, organ dysfunction, thrombus formation, bleeding, and long-term complications in patients. Despite rapid intervention and advances in patient intensive care, why as many as 30% of patients with systemic meningococcal disease develop massive meningococcemia leading to shock and death is still not understood.
authors: Departments of Pediatrics and Medical Biochemistry, University of Oslo, Oslo, Norway. petter.brandtzag@medisin.uio.no
authors: Petter
authors: P
authors: Brandtzaeg
authors: Marcel
authors: M
authors: van Deuren
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000276:immunology; D004269:DNA, Bacterial / Q000097:blood; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008070:Lipopolysaccharides / Q000737:chemistry; D008589:Meningococcal Infections / Q000145:classification* / Q000382:microbiology / Q000503:physiopathology*; D023421:Models, Animal; D009345:Neisseria meningitidis / Q000276:immunology*; D012106:Research; D012772:Shock, Septic / Q000503:physiopathology*; D013552:Swine; D014884:Waterhouse-Friderichsen Syndrome / Q000503:physiopathology*
chemical_list: D004269:DNA, Bacterial; D008070:Lipopolysaccharides