The only natural reservoir of Neisseria meningitidis is the human nasopharyngeal mucosa. Depending on age, climate, country, socioeconomic status, and other factors, approximately 10% of the human population harbors meningococci in the nose. However, invasive disease is relatively rare, as it occurs only when the following conditions are fulfilled: (i) contact with a virulent strain, (ii) colonization by that strain, (iii) penetration of the bacterium through the mucosa, and (iv) survival and eventually outgrowth of the meningococcus in the bloodstream. When the meningococcus has reached the bloodstream and specific antibodies are absent, as is the case for young children or after introduction of a new strain in a population, the ultimate outgrowth depends on the efficacy of the innate immune response. Massive outgrowth leads within 12 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 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.

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

Summary Background Neisseria meningitidis is an important cause of meningitis and septicaemia, but most infected individuals experience a period of asymptomatic carriage rather than disease. Previous studies have shown that carriage rates vary by age and setting; however, few have assessed carriage across all ages. We aimed to estimate the age-specific prevalence of meningococcal carriage. Methods We searched Embase, Medline, Web of Science, the Cochrane Library, and grey literature for papers reporting carriage of N meningitidis in defined age groups in European countries or in countries with a similar epidemiological pattern (where disease caused by serogroups B and C predominates). We used mixed-effects logistic regression with a natural cubic spline to model carriage prevalence as a function of age for studies that were cross-sectional or serial cross-sectional. The model assessed population type, type of swab used, when swabs were plated, use of preheated plates, and time period (decade of study) as fixed effects, with country and study as nested random effects (random intercept). Findings Carriage prevalence increased through childhood from 4·5% in infants to a peak of 23·7% in 19-year olds and subsequently decreased in adulthood to 7·8% in 50-year olds. The odds of testing positive for carriage decreased if swabs were not plated immediately after being taken compared with if swabs were plated immediately (odds ratio 0·46, 95% CI 0·31–0·68; p=0·0001). Interpretation This study provides estimates of carriage prevalence across all ages, which is important for understanding the epidemiology and transmission dynamics of meningococcal infection. Funding None.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(10)70251-6.pdf

Meningococcal carriage by age: a systematic review and meta-analysis

A total of 6234 nasopharyngeal swabs was collected during a survey of the population of Stonehouse, Gloucestershire in November 1986 as part of an investigation into an outbreak of meningococcal disease. The overall meningococcal carriage rate was 10.9%. The carriage rate rose with age from 2.1% in the 0- to 4-year-olds to a peak of 24.5% in the 15- to 19-year-olds, and thereafter declined steadily with age. Male carriers outnumbered female carriers of meningococci by 3:2. Group B (or non-groupable) type 15 sulphonamide-resistant strains which had caused the outbreak were isolated from 1.4% of subjects. The age distribution of carriers of these strains was similar to that of other meningococci apart from an additional peak in the 5-9-year age group and a more rapid decline in carriage with increasing age. Variations in the carriage rates of the outbreak strain were seen in children attending different schools and in the residents of different areas of the town. The low carriage rate of these strains in a community during a prolonged outbreak supports the hypothesis that these organisms are less transmissible but more virulent than other strains of pathogenic meningococci. Carriage of Neisseria lactamica, which is thought to be important in the development of meningococcal immunity, was most frequent in children under the age of 5 years and was six times commoner in this age group than carriage of Neisseria meningitidis. In older children and adults female carriers of N. lactamica increasingly outnumbered males in contrast to the male preponderance observed with meningococcal carriage.

The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica.

This review covers the history of meningococcal meningitis in Africa since epidemics of the infection were first described around 100 years ago. It is possible that an epidemic strain of the meningococcus was introduced into West Africa from the Sudan by pilgrims returning from the Haj around the turn of the century. Since 1905 major epidemics of meningococcal meningitis have occurred in countries of the Sahel and sub-Sahel every few years, culminating in a massive epidemic in which nearly 200,000 cases were reported in 1996. Attempts to control epidemic meningococcal meningitis in Africa by vaccination with meningococcal polysaccharide vaccines have met with only modest success because epidemics can progress with great rapidity and vaccination is often started too late. This situation should be improved as a result of a recent initiative, the International Coordinating Group (ICG), which is contributing to better surveillance in countries at risk and ensuring that vaccine is available when needed. However, in the medium term, the best prospect for the control of meningococcal meningitis in Africa lies in the recent development of polysaccharide-protein conjugate vaccines which, unlike polysaccharide vaccines, are immunogenic in the very young, induce immunological memory and are likely to give long-lasting protection.

Manson Lecture. Meningococcal meningitis in Africa.

Protective activity of vi capsular polysaccharide vaccine against typhoid fever

Asymptomatic carriage of Neisseria meningitidis and Neisseria lactamica was studied in a total of 2,969 healthy infants and children in Danbury, Conn., between October 1971 and June 1975. The prevalence of N. meningitidis averaged 0.71% during the first four years of life and increased to 5.4% by 14--17 years. Rates of carriage of N. lactamica increased from 3.8% in three-month-old infants to a peak of 21.0% at 18 months and then declined to 1.8% by 14--17 years of age. Of the children who acquired N. lactamica, 66% developed fourfold or greater rises in titers of IgG antibody to groups A, B, and/or C meningococci as determined by immunofluorescence compared with only 5% of control children. Of new carriers of N. lactamica, 40% developed increased titers of bactericidal antibody to groups A, B, and/or C meningococci as compared with 7% of noncarriers. Carriage of N. lactamica may assist in the development of natural immunity to N. meningitidis by induction of cross-reactive antibodies.

Carriage of Neisseria meningitidis and Neisseria lactamica in Infants and Children

A cohort of infants, previously immunized once or twice between three and 12 months of age with vaccines containing polysaccharide of groups A and C Neisseria meningitidis, received boosters at two and five and one-half years of age with bivalent A/C vaccine. Antibody concentrations were measured by a radioactive antigen-binding assay. Concentrations of antibody to groups A and C N. meningitidis were 5.59 and 2.86 microgram/ml, respectively, by four years of age. After booster immunization at five and one-half years of age, concentrations of antibody to groups A and C N. meningitidis increased to 15.67 and 7.59 microgram/ml, respectively. Protective levels of antibody to group A meningococci may be achievable throughout early childhood by routine immunization with the A vaccine. Although the group C vaccine is effective in control of epidemics, the rapid decline in the concentration of antibody to group C meningococci following immunization of young children suggests that protection may not be long-lasting.

Kinetics of Antibody Production to Group A and Group C Meningococcal Polysaccharide Vaccines Administered during the First Six Years of Life: Prospects for Routine Immunization of Infants and Children

Infants were immunized with group A Neisseria meningitidis polysaccharide vaccine at two, four, and six months of age. Two lots of group A vaccine that differed in molecular weight were used; lot no. 1980A was of significantly larger molecular size than lot no. A-7. No significant adverse reactions occurred. The geometric mean concentration of serum antibody to group A N. meningitidis one month after the third dose of lot no. 1980A was 0.89 microgram/ml, nearly twice the concentration induced by lot no. A-7 (0.48 microgram/ml). When the infants were 12 months of age, concentrations of antibody in both groups had declined to similar levels, which were still greater than the mean concentration of antibody in unimmunized children. By 18 months of age, the antibody levels of immunized and unimmunized infants were the same. The three-dose schedule resulted in significantly lower concentrations of antibody than previously studied schedules of two doses given three to four months apart.

Antibody responses of human infants to three doses of group A Neisseria meningitidis polysaccharide vaccine administered at two, four, and six months of age.

Thomas F. Draper

Papers

Carriage of Neisseria meningitidis and Neisseria lactamica in Infants and Children

Kinetics of Antibody Production to Group A and Group C Meningococcal Polysaccharide Vaccines Administered during the First Six Years of Life: Prospects for Routine Immunization of Infants and Children

Antibody responses of human infants to three doses of group A Neisseria meningitidis polysaccharide vaccine administered at two, four, and six months of age.