Kimmel accounted for 28% and 27% during that year (CDC 2007). In New Zealand, an epidemic of predominantly serogroup B meningococcal disease has recorded disease rates as high as approximately 500 per 100,000 in Paciﬁc children less then 1 year of age compared with less then 50 per 100,000 children of European descent (O’Hallahan et al 2004). Invasive meningococcal disease usually occurs in persons who are seronegative and subsequently acquire N. menin- gitidis from crowding such as among military recruits and freshmen college students living in residence halls (Bruce et al 2001). The nasopharyngeal carriage rate of N. men- ingitidis has been shown to increase rapidly for ﬁrst year university students living in residence halls (Neal et al 2000). Exposure to tobacco smoke and alcohol-related behaviors are other potential risk factors for meningococcal disease in this population (Harrison et al 1999). Once N. meningitidis attaches to the nasopharyngeal mucosal cells, replicates, and establishes a carrier state, multiple factors determine the occurrence of IMD includ- ing the virulence of the organism and factors affecting host susceptibility (Granoff 2004). The spleen is responsible for clearing meningococci from the blood and anatomic splenectomy has resulted in overwhelming meningococcal sepsis (Condon et al 1994). Patients with functional hypo- or asplenia are also at increased risk for disease (Granoff 2004). Deﬁciencies of terminal complement component, properdin, factor D, and mannan-binding lectin (MBL) have been associated with increased susceptibility to meningo- coccal infection (Pollard and Frasch 2001). The absence of serum bactericidal antibodies (SBAs) to human complement (hSBAs) to serogroup C meningococci, as demonstrated by a titer of less then 1:4, was associated with an increased risk of meningococcal disease in military recruits (Goldschneider et al 1969a). It was later demonstrated that SBAs to rabbit complement (rSBAs) with a titer of less then 1:8 also predict susceptibility to meningococcal disease (Borrow et al 2001). Conversely, a hSBA titer to serogroup C of 4 is considered protective while a rSBA titer of 8 is correlated with at least short-term protection (Borrow et al 2005). Burden of illness Vieusseux in Switzerland ﬁrst described epidemic menin- gococcal disease in 1805, but Weichselbaum ﬁrst identiﬁed the bacterium in 1887 (Barquet et al 1999; Rosenstein et al 2001). Meningitis occurs in about 50% of patients, and in older children and adults is accompanied by sudden head- ache, fever, stiff neck, and sometimes nausea, vomiting, and photophobia (Rosenstein et al 2001). In infants and 740 very young children, fever, poor feeding, and lethargy may be seen initially while nuchal rigidity presents later in the course of the illness (Granoff 2004). A rash is often present but may vary from maculopapular to the classic petechial or purpuric rash. Meningococcal sepsis or meningococcemia occurs in 5%–20% of IMD (Rosenstein et al 2001). It is characterized by sudden fever, petechial or purpuric rash, hypotension progressing to shock, acute adrenal hemorrhage (Waterhouse-Friederichsen syndrome), and multiorgan fail- ure (Rosenstein, Perkins et al 2001). Other forms of IMD include pneumonia, arthritis, pericarditis, and cellulitis (van Deuren et al 2000). The overall case-fatality rate for IMD in the US is approximately 9%–12%, even with appropriate antibiotic treatment, and that for meningococcemia is as high as 40% (Rosenstein et al 2001). However, the fatality rate can vary according to the affected population and the meningococcal serogroup. In New Zealand, the average case-fatality rate for serogroup B IMD is 4.3% (O’Hallahan et al 2004). In a study of 295 cases of IMD in Maryland, USA from 1992 to 1999, persons ages 15–24 years old accounted for 24% of IMD cases and had a fatality rate of 23% compared with 4.6% of those younger than 15 years and 17% of those older than 24 years (Harrison et al 2001). Of the 14 fatalities for which serogroup was known, serogroups C and Y accounted for 57% and 29%, respectively, of fatalities in this age group (Harrison et al 2001). Consequently, more then 85% of these deaths were potentially preventable by the tetravalent (Groups A, C, Y, and W-135) meningococcal vaccines. Invasive meningococcal disease may also cause sequelae such as hearing loss, neurologic deﬁcits, or limb loss in up to 11%–19% of cases (Rosenstein et al 2001). A review of IMD in Barcelona from 1987 to 1992 found a sequelae rate of 8.2% for meningitis, 3.5% for meningococcemia with meningitis, and 1.5% for meningococcemia with an overall rate of 4% (Barquet et al 1999). All patients who had neuro- logic sequelae had meningitis while meningococcemia was associated with sequelae such as limb amputation (Barquet et al 1999). Outbreaks of meningococcal disease Household contacts of patients with IMD have a 500–800 times greater risk of meningococcal disease than the general rate and should be given chemoprophylaxis (Bilukha and Rosenstein 2005). They are candidates for immunization with meningococcal vaccine, but this does not substitute for chemoprophylaxis because of the time delay in developing immunity. Chemoprophylaxis should also be given to close Therapeutics and Clinical Risk Management 2008:4(4)