This genetically determined trait is referred to as endotoxin responsiveness. h to fulminant meningococcal sepsis (FMS), characterized by high intravascular concentrations of endotoxin that set free high concentrations of proinflammatory mediators. These mediators belonging to the complement system, the contact system, the fibrinolytic system, and the cytokine system induce shock and diffuse intravascular coagulation. FMS can be fatal within 24 h, often before signs of meningitis have developed. In spite of the increasing possibilities for treatment in intensive care units, the mortality rate of FMS is still 30%. When the outgrowth of meningococci in the bloodstream is impeded, seeding of bacteria in the subarachnoidal compartment may lead to overt meningitis Gefitinib-based PROTAC 3 within 24 to 36 h. With appropriate antibiotics and good clinical surveillance, the mortality rate of this form of invasive disease is 1 to 2%. The overall mortality rate of meningococcal disease can only be reduced when patients without meningitis, i.e., those who may develop FMS, are recognized early. This means that the fundamental nature of the disease as a meningococcus septicemia deserves more attention. In 1919, long before the era of antibiotics and intensive care, Herrick stated with respect to meningococcal infections, no other infection so quickly slays (217). More than 80 years later, this still holds true. Because healthy young children are primarily the victims of this disease, its incidence continues to increase, and the mortality is still 10% (204, 346, 348, 376); social, medical and scientific vigilance is still required (126). is an exclusively human, gram-negative, bean-shaped pathogenic diplococcus that, similar to other gram-negative bacteria, is surrounded by an outer membrane composed of lipids, outer membrane proteins (OMPs), and lipopolysaccharides. Moreover, pathogenic meningococci are enveloped by a Gefitinib-based PROTAC 3 polysaccharide capsule attached to this outer Gefitinib-based PROTAC 3 membrane. Meningococci reveal more genetic diversity than most other pathogenic human bacteria. This is explained partly by horizontal intraspecies recombination and incorporation from closely related species (80). Traditionally, strains were characterized by using antibodies that recognize surface-exposed epitopes on the capsule or the outer membrane. By this technique, 13 serogroups (identifying capsule antigens), 20 serotypes (identifying class 2/3 OMP antigens), and 10 Rabbit Polyclonal to SPON2 subtypes (identifying class 1 OMP antigens) have been defined (151). An example of this serological typing is B:4:P1.4, indicating serogroup B, serotype 4, and subtype P1.4. By using the antigenic properties of lipopolysaccharide, renamed lipooligosaccharide (LOS) because of its relatively short sugar chain, another 13 immunotypes, designated by the letter L, can be distinguished (298, 413). Further additional typing is possible by using the antigenic properties of immunoglobulin A1 (IgA1) proteases and pili (452). Serotyping is of great importance for the development of vaccination strategies. However, although phenotypic characterization may reveal close genetic relatedness, serotyping is not suitable for modern epidemiologic purposes (80). Typing schemes based on variation of a few genes which are probably under selection pressure will not identify the overall relatedness of the chromosomal genome of (80). By using genetic approaches, in particular multilocus Gefitinib-based PROTAC 3 enzyme electrophoresis, which identifies naturally occurring allelic variation in multiple chromosomal housekeeping genes, a better insight into the epidemiology and clonal expansion of disease-causing can be gained. Other techniques used to this end are DNA fingerprinting and PCR (36, 148, 424, 541). EPIDEMIOLOGICAL TRENDS Meningococcal disease occurs worldwide as endemic infections (2, 80, 242, 346, 383, 421). Strains of serogroups B and C cause the majority of infections in industrialized countries. Strains of serogroups A and, to a lesser extent, C dominate in third-world countries (2, 80, 242, 315, 346, 383, 421). The incidence of meningococcal disease during the last 30 years varies from 1C3/100,000 in most industrialized nations to 10C25/100,000 in some third-world countries. These different attack rates reflect the different pathogenic properties of strains and different socioeconomic, environmental, and climatological conditions. Sub-Saharan Africa has a special epidemiological pattern. This region, designated the meningitis belt, was first described by Lapeyssonnie in 1963 and comprised 10 countries i.e., Burkina Faso, Ghana, Togo, Benin, Niger, Nigeria, Chad, Cameroon, Central African Republic, and The Sudan (271). Later, Ethiopia, Mali, Guinea, Senegal, and the Gambia were added, to form what Gefitinib-based PROTAC 3 is presently denoted the expanded meningitis belt (183, 383). In this region, meningococcal disease caused by serogroup A occurs in yearly recurrent waves. The disease attack rate rises at the end of the dry season and declines rapidly after the beginning of the rainy season (2, 271, 315, 346, 383, 421). During epidemic peaks, the disease incidence may approach 1,000/100,000 inhabitants (383). Initially, a cyclic pattern with epidemics.