Classification and Pathogenesis of Meningococcal Infections
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 c
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seria meningitidis is an obligate human Gram-negative diplococcus residing asymptomatically in the upper respiratory tract (1). The highest carriage rate is found among adolescents and young adults representing the main reservoir of the bacterium. Few young children carry meningococci (1). Most carried strains never cause
Myron Christodoulides (ed.), Neisseria meningitidis: Advanced Methods and Protocols, Methods in Molecular Biology, vol. 799, DOI 10.1007/978-1-61779-346-2_2, © Springer Science+Business Media, LLC 2012
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P. Brandtzaeg and M. van Deuren
invasive disease. A limited number of meningococci belonging to specific clones or clonal complexes with serogroups A, B, C, Y, and W135 cause >95% of systemic meningococcal disease (SMD) (1). Encapsulated meningococci expressing pili, opacity proteins, and other subcapsular adhesion molecules are transferred by droplets or by direct contact (kissing) from an asymptomatic carrier to a nonimmune person. After attachment to nonciliated columnar epithelial cells in the nasopharynx or the epithelium covering the tonsils, meningococci adapt and start to proliferate. Type 4 pili and various outer membrane proteins including opacity proteins undergo phase variation (2). Studies in vitro suggest that N. meningitidis may transverse the epithelial cells through “parasite directed endocytosis” (3). It is assumed that meningococci enter the blood stream through the capillaries and small veins in the underlying submucosal tissue. Survival and growth of encapsulated N. meningitidis in the circulation is a fundamental requirement for developing SMD. Clinical disease usually develops within a week following breach of the mucosal barrier. A century ago, before any effective treatment existed, 70–90% of the patients died during the natural course of infection (4). After the introduction of antimeningococcal serum therapy in 1905, the case fatality rate (CFR) declined to approximately 40% (4). Treatment with sulfonamides in 1937 and with penicillin in 1945 resulted in a further decline of the CFR to approximately 10%. In the last decade, the CFR has ranged from 7 to 11% in Europe and the USA for sporadic cases, increasing to above 20% in outbreak situations (5–7). Two characteristics make N. meningitidis unique among human pathogens: (1) The propensity to invade the meninges and (2) the ability to proliferate rapidly in the blood leading to shock and multiple organ failure in as many as 30% of the patients contracting serogroup B and C strains (6, 8, 9). Meningococci are known among physicians, epidemiologists, and lay people as the bacterium causing outbreaks of meningitis. In industrialized countries, physicians should rightly fear N. meningitidis as the bacterium that may cause overwhelming septicemia, shock, and death. Meningococci may kill previously healthy children or adults within 12–24 h (6, 10, 11). Septic shock and multiple organ failure is the direct cause of death in nine out of ten patients with lethal meningococcal infections in Western countries (Table 1) (6, 8–
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