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Epidemiology of Neisseria meningitidis infection

Epidemiology of Neisseria meningitidis infection
Literature review current through: Jan 2024.
This topic last updated: May 10, 2022.

INTRODUCTION — Meningococcal disease, especially meningococcal meningitis, is one of the most devastating infections in an individual or community; reports of documented or suspected cases can engender considerable panic, even among well-informed hospital personnel. Part of the explanation for this phenomenon is the fact that meningitis due to Neisseria meningitidis tends to strike young, previously well individuals and can progress over a matter of hours to death.

Mortality can be very high if the infection is not treated appropriately, and long-term sequelae can be severe even in successfully managed cases. The mortality and morbidity from meningococcal disease has changed very little since the 1950s, principally due to the inability to effectively manage the endotoxin-induced vascular collapse frequently caused by this organism.

N. meningitidis can cause both endemic and epidemic infection. Large numbers of individuals can become infected in a population within a short space of time. With the reduction in cases of meningitis due to Haemophilus influenzae, N. meningitidis has now become the second leading cause of meningitis in the United States. The majority of cases of meningococcal infection occur in young children and teenagers.

This pathogen has the added capacity to cause epidemics in which all age groups in the entire population become at risk. While the worst of these epidemics have recently been largely confined to less well-developed areas of the world, epidemics have occurred in areas of Europe and North America where there are very high standards of living. Epidemic meningococcal infection can be a terrifying experience for the population affected. The progression of disease can be very rapid. The clinical features can be quite dramatic with profound shock, subcutaneous and gingival hemorrhage, thrombosis of vessels to extremities, delirium, and coma leading to death within 24 hours.

The epidemiology of infections due to N. meningitidis will be reviewed here. The microbiology, pathobiology, clinical features, diagnosis, treatment, and prevention of this infection are discussed separately. (See "Microbiology and pathobiology of Neisseria meningitidis" and "Clinical manifestations of meningococcal infection" and "Diagnosis of meningococcal infection" and "Treatment and prevention of meningococcal infection" and "Meningococcal vaccination in children and adults".)

ATTACK RATES

United States — The annual incidence of invasive meningococcal disease in the United States varies in multiyear cycles; the most recent peak occurred during the mid-1990s (figure 1). Subsequently, the incidence has declined annually [1,2]. Routine use of meningococcal conjugate vaccine was recommended for adolescents in 2005. The annual incidence of meningococcal disease decreased between 2006 and 2015; during this time, the average annual incidence was 0.26 cases per 100,000 population [3,4]. The rate in 2017 reduced further to 0.11 out of 100,000. Deaths still occurred in approximately 15 percent of cases [5].

Between 2006 and 2015, there were major changes in the incidence, age, and serogroup distribution of meningococcal disease in the United States [4]:

During this time, annual incidence dropped almost 78 percent (from 0.40 cases to 0.14 cases per 100,000). Among children <1 year of age, the incidence dropped (from 11 cases to 0.73 cases per 100,000); this was associated with a major shift in the median patient age from 17 to 42 years of age (figure 2).

The incidence of serogroups B declined from 0.25 to 0.05 cases per 100,000 between 2006 and 2015 [4]; among college students between 2014 and 2016, the average annual incidence was 0.17 cases per 100,000 [6]. Between 2006 and 2015, the incidence of serogroup C declined from 0.38 to 0.01 cases per 100,000, the incidence of serogroup Y declined from 0.42 to 0.02 cases per 100,000, and the incidence of serogroup W (and other serogroups) remained stable.

The highest case-fatality ratios occurred with infections caused by serogroup W (21 percent) and serogroup C (14 percent). The highest incidence of disease occurred among infants two to three months of age (25 percent), and the highest mortality occurred in patients over 85 years of age (<28 percent). The incidence among males was slightly higher than among females, and the incidence was higher among African-Americans than individuals of other racial groups (0.27 versus 0.20 cases per 100,000).

The emergence of infections due to serogroup W ST-11 has been the cause of some concern [7]. The age distribution of these infections is somewhat different in that the infection has been observed among individuals >18 years. A similar increase in incidence of serogroup W ST-11 strains has been observed in eastern Europe and Great Britain.

Meningococcal infection displays seasonal variation in attack rates, which are highest in February and March and lowest in September. There is no predisposition by sex. The predominant serogroups causing infection in the United States are serogroups B, C, and Y, each accounting for approximately one-third of cases [3]. The proportion of cases caused by each serogroup varies by age. Serogroups C, Y, and W cause 73 percent of cases among individuals ≥11 years of age. In contrast, approximately 60 percent of disease among children aged 0 to 59 months is caused by serogroup B.

Issues related to clusters of serogroup C meningococcal disease among men who have sex with men in the United States are discussed below. (See 'Men who have sex with men' below.)

Outside the United States

Serogroup A — Large-scale epidemics occur with frequency in Africa, parts of Asia, South America, and the countries of the former Soviet Union. These epidemics are most commonly caused by N. meningitidis serogroup A and occasionally by serogroup C.

Epidemics of meningococcal infection occur at irregular intervals, often every 7 to 10 years in sub-Saharan Africa [8,9]. The case rate during these epidemics can be as high as 1 in 1000 total population and 1 in 100 for children under two years of age. The largest outbreak of Neisseria meningitidis serogroup C in sub-Saharan Africa occurred in 2015; 8500 suspected cases of meningococcal meningitis and 573 deaths were reported to the WHO [10].

The World Health Organization (WHO) has endorsed a surveillance strategy to predict epidemics early and initiate vaccination drives. A study from Mali showed that detection of 5 cases per 100,000 population in one week was an appropriate threshold for alerting officials that vaccination might be required and 10 cases per 100,000 in one week confirmed regional epidemic activity with few false-positive results [11]. These numbers were in contrast to the WHO recommended threshold of 15 cases per 100,000 averaged over two weeks.

In one epidemic in Nairobi, Kenya, the attack rate was 2.5 cases per 10,000 population, with a case-fatality rate of approximately 10 percent [8,9]. Areas that included Nairobi's largest dense and poor urban settings were particularly affected. This epidemic displayed an unusual age distribution, with high attack rates among 20- to 29-year-olds.

Serogroup C — The largest N. meningitidis serogroup C epidemic ever reported occurred in Nigeria in 2016 to 2017 [12]. There were more than 14,000 suspected cases (fever >100.4°F plus one or more meningeal signs). Among the 1339 individuals who underwent laboratory testing, 32 percent were positive for bacterial pathogens, of which 83 percent had N. meningitidis serogroup C. This finding prompted vaccination of two million individuals between ages 2 and 29 years, which was effective in truncating the epidemic.

Serogroup W — Serogroup W represents one of the less common serogroups of meningococci. The largest outbreak of infection due to this strain occurred among more than 400 pilgrims returning in 2000 and 2001 from the Hajj in Mecca, Saudi Arabia [13,14]. Cases were detected in several countries in Asia, Europe, and the United States [15]. Three cases surfaced in the United States, one in a returning pilgrim and two in contacts of pilgrims [13].

Serogroup W may also play a role in endemic infection. This was illustrated in a national surveillance study in South Africa in which the emergence of endemic serogroup W was associated with an increase in the incidence and severity of invasive meningococcal disease [16]. From 2000 through 2005, 2135 cases of invasive meningococcal disease were reported, 52 percent of which occurred in a single province. In this region, rates of disease increased from 0.8 cases per 100,000 persons in 2000 to 4.0 cases per 100,000 in 2005, and the proportion of cases due to serogroup W increased from 7 percent in 2000 to 75 percent in 2005. Overall case-fatality rates doubled from 11 percent in 2003 to 22 percent in 2005. Serogroup W was more likely to cause meningococcemia than serogroup A.

RATIONALE FOR VACCINATION — The rationale for meningococcal vaccination in selected individuals is discussed below. Issues related to meningococcal vaccination are discussed separately. (See "Meningococcal vaccination in children and adults".)

N. meningitidis can cause both endemic and epidemic infection. Meningococcal infections are endemic in the United States, and the annual incidence of invasive meningococcal disease varies in multiyear cycles; the most recent peak in incidence occurred during the mid-1990s (figure 1) [1]. Between 2005 and 2011, the incidence of meningococcal disease in the United States was 0.3 cases per 100,000 population [3]. Disease rates are almost 10 times higher in children below two years of age than in the overall population. (See 'United States' above.)

Outbreaks of meningococcal infection on college campuses have attracted considerable attention [17-21]. A retrospective cohort study did not reveal an increase in the incidence of meningococcal infection in college students compared with age-matched controls (1.74 versus 1.44 per 100,000) [17]. However, among affected college students, the rates of illness were higher for those residing on campus. Another case-control study performed in college students determined that the incidence of infection was lower than the general population of 18- to 23-year-old nonstudents (0.7 versus 1.4 per 100,000); however, the incidence was highest in freshmen living in dormitories (5.1 per 100,000), and the risk for disease by multivariate analysis was 3.6 for this group compared with other college students [18]. A study from the United Kingdom also found that having a high proportion of first-year students in a residence hall increased the risk for meningococcal infection [19].

Large-scale epidemics occur with considerable frequency in an area that crosses the waist of sub-Saharan Africa [8,9]. The case rate during these epidemics can be as high as 1 in 1000 total population and 1 in 100 for children below two years of age. Travelers may be at risk for acquiring meningococcal infection, especially when traveling to regions at risk for epidemics or hyperendemic for the disease and for those with extensive contact with local residents. The Hajj pilgrimage to Mecca has been associated with outbreaks of meningococcal infection; pilgrims are required by the government of Saudi Arabia to be vaccinated. (See "Immunizations for travel", section on 'Meningococcal vaccine'.)

Outbreaks of invasive serogroup C meningococcal disease have been reported in men who have sex with men. This is discussed further separately.

The distribution of serogroups of N. meningitidis causing infection can differ depending upon the region of the world. In a United States survey from 1992-1996, serogroups C, B, and Y accounted for 35, 32, and 26 percent of isolates, respectively [22]. In a subsequent surveillance study (1996 to 2015), serogroups C, B, and Y were responsible for 23, 36, and 28 percent of isolates, respectively [4]; serogroup W accounted for approximately 7 percent of cases. The majority of invasive infections in England and Wales are caused by serogroups B and C [23,24]. Epidemics in Africa and elsewhere in the world are most frequently due to serogroup A and occasionally serogroup C. W is an uncommon serogroup but was responsible for a large number of cases among pilgrims returning from the Hajj in Saudi Arabia in 2000 [13]. (See 'Genetics of outbreak strains' below.)

RISK FACTORS FOR EPIDEMICS — The reason for the epidemic spread of the meningococcus is not known. The organism is considered a respiratory pathogen and spread is most likely by the aerosol route. It is clear that the high attack rates seen in the less well-developed countries are in part due to poverty and the consequences of crowding, poor sanitation, and malnutrition.

Factors such as herd immunity and specific virulence properties associated with epidemic strains have been implicated as factors in the rapid spread of infection in these situations [25]. Clonal analysis of strains from one epidemic in central and east Africa indicated that the epidemic strain had arisen in central Asia almost seven years prior; spread occurred through Northern India and Pakistan to Saudi Arabia and then to Africa via pilgrims from Mecca [26]. A number of American pilgrims returning from Mecca at that time were found to have nasopharyngeal colonization with this epidemic strain [27].

RISK FACTORS FOR ACQUISITION OF INFECTION — A number of environmental and host factors have been associated with an increased risk for endemic acquisition of N. meningitidis infection. The major associated factor is nasopharyngeal carriage.

Nasopharyngeal carrier state — The importance of nasopharyngeal carriage of the meningococcus in the transmission of the organism and the development of disease was appreciated early based upon the experience with military recruits [28,29]. Epidemic infections in American military recruit camps were a major problem prior to the introduction of vaccination. Throughout the nineteenth century, the unique susceptibility of military recruits can be attested by the clinical descriptions of this infection that can be found in the records of the Crimean and American Civil Wars. Since the introduction of vaccination of all recruits in the United States in 1972 with a tetravalent vaccine containing serogroup A, C, Y, and W polysaccharides, epidemics have not occurred [30].

However, vaccination of recruits is not universal around the world. The dynamics of carriage was studied in a 1998 report of military recruits in Denmark [31]. The rate of carriage in 1069 recruits followed for three months during each of three separate seasons was 39 to 47 percent at entry and did not change appreciably with time or season. Both loss of carriage and acquisition was documented in individuals, with 34 percent experiencing one or more change in carrier status over time. No differences were observed in the acquisition of invasive strains, which had caused disease in other subjects, from other strains in this study.

Another study examined the immune response in military recruits carrying the meningococcus or acquiring the organism in the pharynx during basic training [32]. Increases in antibody to the colonizing strains were documented; individuals colonized with more than one strain made antibody responses only to the newly acquired strain. Serum bactericidal activity to the homologous strains was also demonstrated.

Intimate contacts of cases, including family members, college roommates, and nursery school classmates, are at 100- to 1000-fold increased risk of acquiring meningococcal infection. In one study of contacts of patients with meningococcal infection from Norway, household and kissing contacts had an increased frequency of carriage of the pathogenic strain compared with less close contacts (12.4 versus 1.9 percent) [33]. Such individuals should be monitored closely for the development of co-primary cases (cases which arise within 48 hours of the primary case) and be given chemoprophylaxis to prevent secondary cases of infection [34]. (See "Treatment and prevention of meningococcal infection", section on 'Antimicrobial chemoprophylaxis'.)

In a study of 2507 university students conducted in the United Kingdom, meningococcal carriage rates increased substantially during the fall term [35]. During the first week of school (early October), the rate rose from 7 to 23 percent and the average rate for those living in dormitories increased from 14 percent at the beginning of October to 34 percent in December.

When testing for nasopharyngeal carriage, cultures should be taken from the nasopharynx since the rate of salivary carriage is very low (0.4 versus 35 percent in the nasopharynx or tonsils in a series of 258 college students) [36].

In addition to outbreaks and military recruits, N. meningitidis is occasionally identified on a throat culture. This issue is discussed elsewhere.

Complement deficiency — Complement deficiency involving early and late components of the complement system have been associated with increased susceptibility to meningococcal infection [37-46]. In one study including 20 patients with sporadic meningococcal infection, six were demonstrated to have a complement deficiency, three in terminal complement protein(s) and three in multiple factors with accompanying underlying diseases [42]. (See "Inherited disorders of the complement system".)

The likelihood of an underlying terminal complement or properdin deficiency is higher among patients who have their first episode of Neisserial disease after age 10, are infected with an unusual serogroup of N. meningitidis, or suffer relapses or recurrences [40]. These patients usually have a milder course and the mortality rate is lower compared with other populations (3 to 4 percent versus 6 to 12 percent) [40,41].

The host defense defects associated with a terminal complement component deficiency are associated with meningococcal disease and disseminated gonococcal disease [37,45]. Deficiencies of C3 and properdin are also associated with defective defense against Neisserial species, which is probably due to the key role of these components in efficiently activating C5 to C9 [47]. Polymorphisms in the genes for complement factor H (CFH), a regulator of complement activity, have also been associated with meningococcal susceptibility [48,49].

A family with properdin deficiency has also found to have a high rate of fatal meningococcal disease [40]. The bactericidal defect was demonstrated to be correctable in these patients via vaccination. Use of the meningococcal tetravalent capsular polysaccharide conjugate vaccine in individuals deficient in late-complement components may focus host defense on phagocytosis rather than serum bactericidal activity, which is deficient in these patients [43].

Use of eculizumab — Eculizumab is a monoclonal antibody terminal complement inhibitor used for treatment of hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria. (See "Complement-mediated hemolytic uremic syndrome in children" and "Treatment and prognosis of paroxysmal nocturnal hemoglobinuria".)

Administration of eculizumab has been associated with a 1000-fold to 2000-fold increased incidence of meningococcal disease. Life-threatening and fatal meningococcal infections have occurred in patients treated with eculizumab [50].

Issues related to prevention of meningococcal infection in patients treated with eculizumab are discussed separately. (See "Treatment and prevention of meningococcal infection", section on 'Patients receiving C5 inhibitors'.)

HIV infection — There appears to be an increased risk of invasive meningococcal disease in people living with HIV. Although studies in the preantiretroviral therapy (ART) era did not find an association between HIV infection and invasive meningococcal disease [51-54], studies in the ART era have suggested that HIV-infected patients are at increased risk for invasive meningococcal disease [3,55-58].

In one retrospective cohort study using surveillance data on cases of invasive meningococcal disease in New York City from 2000 to 2011, the relative risk of invasive meningococcal disease among persons with HIV was 10 (95% CI 7.2-14.1) [55]. Among persons with HIV, those with invasive meningococcal disease were 5.3 times (95% CI 1.4 to 20.4 times) as likely as age-matched controls to have CD4+ counts <200 × 106 cells/microL. The authors of this study hypothesized that no association between HIV infection and invasive meningococcal disease was observed in the pre-ART era because HIV-infected patients had a shorter life span and invasive meningococcal disease is rare, making it difficult to detect an association.

Meningococcal vaccination in patients with HIV is presented separately. (See "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

Men who have sex with men — The incidence of meningococcal disease is increased among men who have sex with men (MSM) compared with non-MSM [59]. The association between HIV infection and invasive meningococcal disease is discussed above. (See 'HIV infection' above.)

Several clusters of serogroup C meningococcal disease among MSM have been reported in the United States:

In 2012, an outbreak of invasive serogroup C meningococcal disease was detected among MSM in New York City [60-63]. The incidence rate of invasive meningococcal disease among MSM aged 18 to 64 years in New York City in 2012 was 12.6 per 100,000 persons (compared with 0.16 per 100,000 persons among non-MSM males of the same age) [62].

Between 2010 and March 2013, 22 cases were detected [64]. The mean age was 34 years; 50 percent occurred in African Americans, 55 percent occurred in HIV-infected individuals, and 32 percent were fatal [63]. In Los Angeles, four cases of invasive meningococcal disease were reported in MSM between December 2012 and June 2013, and four additional cases were reported in 2014 [63,65].

In 2016, 25 outbreak-associated cases were reported in Southern California [66]. In a subsequent report including 74 cases of meningococcal disease among MSM and 453 cases among non-MSM, the incidence of meningococcal disease among MSM was 0.56 cases per 100,000 population compared with 0.14 among non-MSM, for a relative risk of 4.0 [67].

In April 2022, a large outbreak of serogroup C meningococcal disease was reported in Florida, primarily involving MSM, including those living with HIV [21]. As of May 2022, the outbreak is ongoing.

Serogroup C meningococcus disease has also been reported among MSM in Europe [68].

Recommendations for meningococcal vaccine in MSM are discussed in a separate topic review. (See "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk' and "Meningococcal vaccination in children and adults", section on 'Outbreak control'.)

Other host factors — A variety of other host factors have also been associated with increased susceptibility to meningococcal infection [69]. This issue was directly addressed in a matched cohort study of 114 adolescents (15 to 19 years of age) with meningococcal disease [70]. Significant independent risk factors for meningococcal disease were:

History of preceding illness (matched odds ratio [OR], 2.9; 95% CI, 1.4-5.9)

Intimate kissing with multiple partners (matched OR, 3.7; 95% CI, 1.7-8.1)

Being a university student (matched OR, 3.4; 95% CI, 1.2-10)

Preterm birth (matched OR, 3.7; 95% CI, 1.0-13.5)

Factors associated with protection from disease were:

Religious observance (matched OR, 0.09, 95% CI, 0.02-0.6)

Meningococcal vaccination (matched OR, 0.12; 95% CI, 0.04-0.4)

University students in the United States are also at increased risk for serogroup B meningococcal infection, specifically. Surveillance data from 2014 to 2016 found that although the incidence of overall meningococcal infection among persons aged 18 to 24 years was low (0.17 cases per 100,000), university students had an increased risk of infection with meningococcal serogroup B (relative risk 3.54, 95% CI 2.21-5.41) [6]. In 2022, a cluster of serogroup B cases were reported among college and university students in Florida [21].

Smoking appears to be another risk factor for meningococcal infection. In a study of 311 marine recruits, both active and passage cigarette smoking were implicated as risk factors for pharyngeal carriage of N. meningitidis [71]. In other studies, smoking has been associated with meningococcal disease [72,73]. In one report, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children less than 18 years of age [72].

With respect to passive smoking, it has been suggested that the increase in risk is more likely due to exposure to smokers, who are more likely to be carriers of N. meningitidis, than to exposure to smoke [74].

A number of other risk factors have been described. These include:

Attendance at a bar or disco [73,75]

Preceding respiratory tract infection, particularly with influenza virus

In addition, a variety of genetic factors may affect susceptibility to meningococcal infection:

Variants in host alleles for mannose-binding lectin (MBL), a serum protein that activates the classical complement pathway and also serves as an opsonin, were associated with an increased susceptibility to meningococcal infection in a study comparing children with meningococcal infection to controls in two separate cohorts [46]. Homozygosity for variant MBL alleles was associated with a higher incidence of meningococcal infection (8 versus 2 percent in hospitalized patients and 8 versus 3 percent in a community population).

The mechanism of such an effect remains uncertain. An in vitro study using serum from patients with terminal complement and MBL deficiency failed to demonstrate a significant role for MBL in opsonophagocytosis of meningococci [76].

Single nucleotide polymorphisms (SNPs) in the human genes for surfactant proteins (SP-A1, SP-A2, and SP-D), proteins responsible for binding microorganisms such as N. meningitidis in the respiratory tract, were analyzed in 303 patients with meningococcal disease and 22 healthy control subjects [77]. Homozygosity of allele 1A(1) of SP-A2 significantly increased the risk of meningococcal disease (odds ratio 7.4), while allele 1A(5) significantly reduced the risk (odds ratio 0.3). Genetic variations in SP-A1 and SP-D were not associated with meningococcal disease.

Variations in the genes for interleukin (IL)-1 and its receptor did not influence susceptibility to meningococcal infection but did affect survival in a study from England and Wales [44].

Occupational exposure — Occupational acquisition of meningococcal disease has been described rarely in healthcare workers and first responders (eg, ambulance workers, police officers) [78-80], as well as in laboratory workers who handle N. meningitidis [81,82].

In a study that assessed the risk of laboratory-acquired meningococcal disease by requesting information on email listservs of infectious disease, microbiology, and infection control professional organizations, 16 cases of probable laboratory-acquired meningococcal disease were identified worldwide between 1985 and 2001; half of the cases were fatal [81]. All cases occurred in clinical microbiologists, and in 15 of 16 cases (94 percent), N. meningitidis isolates were handled without respiratory protection. The estimated attack rate among microbiologists in the United States between 1996 and 2001 was 13 per 100,000 microbiologists compared with 0.2 per 100,000 among the general adult United States population.

GENETICS OF OUTBREAK STRAINS

United States — In a large population-based survey of meningococcal disease in the United States noted above, serogroups C, B, and Y accounted for 35, 32, and 26 percent of isolates, respectively [22]. The proportion of cases caused by serogroup Y infection increased during the study period (11 percent in 1992 to 33 percent in 1996). Retrospective surveillance in Chicago also confirmed this trend [83]. Twenty-five percent of 214 cases of meningococcal infection were serotype Y; the attack rate for this serotype increased from 0.04 per 100,000 in 1991 to 0.82 per 100,000 in 1995.

Since the introduction of a quadrivalent meningococcal conjugate vaccine that protects against serogroups A, C, W, and Y in the United States in 2005, several outbreaks of meningococcus serogroup B have occurred on college campuses. Prior to the routine use of this vaccine in adolescents, outbreaks on college campuses were typically caused by meningococcus serogroup C [84]. Between 2008 and 2010, 13 cases of meningococcal disease occurred at a college in Ohio, 10 of which were caused by meningococcus serogroup B [84]. In 2013, eight cases of meningococcus serogroup B infection were detected over an eight month period at Princeton University in New Jersey [85]. In November 2013, three cases of meningococcus serogroup B infection were detected at the University of California, Santa Barbara. In January 2016, three cases of meningococcus serogroup B infection were detected at Santa Clara University [86].

Prior to World War II, periodic epidemics of meningococcal infection ravaged American cities, primarily caused by serogroup A. With increasing standards of living, these epidemics have abated in this country and infection due to this serogroup has virtually disappeared.

Outside the United States — The genetics of the organisms causing epidemics in Africa have also been examined [87]. Clone III-1 of N. meningitidis serogroup A has been traced to spread from an area which crosses the waist of sub-Saharan Africa all the way to South Africa [9,88]. Techniques used to study these organisms include ribotyping, pulsed-field gel electrophoresis, multilocus enzyme electrophoresis, and polymerase chain reaction (PCR).

N. meningitidis can be organized into clonal complexes (CCs), which are groups of strains defined by multilocus sequence-type analysis based on housekeeping genes [89]. Sequence types (STs) that share a minimum of four identical alleles with a central (ancestral) ST are assigned to a CC; CCs are remarkably stable. Genomic analysis has demonstrated that the majority of cases of invasive meningococcal disease are caused by isolates that belong to a limited number of CCs, known as hyperinvasive lineages [89-91].

A review of the global incidence of serogroup B meningococcus between 2000 and 2015 noted a yearly incidence of less than 2 per 100,000 people in most countries; within these relatively low-incidence rates, there was substantial variation between countries [92]. The incidence was notably higher in Australia, Europe, North American, and South America; China and India had reports of only sporadic cases, and, except for South Africa, sub-Saharan Africa had a near absence of disease.

In the developed nations of Western Europe, epidemics due to serogroup B meningococcus have occurred since the mid-1980s. Norway suffered such an epidemic with case rates of 1 in 10,000 individuals from 1985 to 1989. A high attack rate was seen among children as old as teenagers in this epidemic [93]. In Belgium, 420 meningococcal isolates were characterized and compared with reference strains from the Netherlands and the rest of Europe, confirming the spread of epidemic N. meningitidis serogroup B from the Netherlands to Belgium [94].

Outbreaks of a new serogroup C meningococcus causing disease emerged during 2003 to 2005 (10 outbreaks with 72 cases) in Anhui province, China [95]. Molecular analysis established that the strain (sequence type-4821) did not belong to any of the previously reported sequence types, forming a new hypervirulent lineage; this strain should be monitored for future spread in China and the rest of the world.

SUMMARY

Meningococcal disease, especially meningococcal meningitis, is one of the most devastating infections in an individual or community; reports of documented or suspected cases can engender considerable panic, even among well-informed hospital personnel. Part of the explanation for this phenomenon is the fact that meningitis due to Neisseria meningitidis tends to strike young, previously well individuals and can progress over a matter of hours to death. (See 'Introduction' above.)

Meningococcal infections are endemic in the United States, and the annual incidence of invasive meningococcal disease varies from 0.5 to 1.5 cases per 100,000 population in multiyear cycles. The most recent peak in incidence occurred during the mid-1990s (figure 1). Disease rates are almost 10 times higher in children below two years of age than in the overall population. The predominant serogroups causing infection in the United States currently are serogroups B, C, and Y. (See 'United States' above.)

Large scale epidemics still occur with frequency in Africa, parts of Asia, South America, and the countries of the former Soviet Union. These epidemics are most commonly caused by N. meningitidis serogroup A and occasionally by serogroup C. (See 'Outside the United States' above.)

Epidemics of meningococcal infection occur at irregular intervals, often every 7 to 10 years in sub-Saharan Africa. The case rate during these epidemics can be as high as 1 in 1000 total population and 1 in 100 for children under two years of age. (See 'Outside the United States' above.)

The reason for the epidemic spread of the meningococcus is not known. The organism is considered a respiratory pathogen and spread is most likely by the aerosol route. It is clear that the high attack rates seen in the less well-developed countries are in part due to poverty and the consequences of crowding, poor sanitation, and malnutrition. Factors such as herd immunity and specific virulence properties associated with epidemic strains have been implicated as factors in the rapid spread of infection in these situations. (See 'Risk factors for epidemics' above.)

A number of environmental and host factors have been associated with an increased risk for endemic acquisition of N. meningitidis infection. The major associated factor is nasopharyngeal carriage. Complement deficiency involving both the late and early components of the complement system have also been associated with increased susceptibility to meningococcal infection, as has administration of eculizumab. (See 'Risk factors for acquisition of infection' above.)

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Topic 1298 Version 50.0

References

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