Nasopharyngeal carriage of Neisseria meningitidis in general population and meningococcal disease

Nasopharyngeal carriage of Neisseria meningitidis was determined in the normal healthy population in Delhi at monthly intervals for a period of 2 years from January, 1986 to December, 1987. Of a total of 6513 individuals screened only 107 (1.64 per cent) were found to carry Neisseria meningitidis serogroup A. There was no age and sex difference in carriage. During the same period, data of laboratory confirmed cases of meningitis due to N. meningitidis serogroup A was obtained from 6 hospitals of Delhi which acted as sentinel centres. Of the total 11,870 pyogenic C.S.F. samples processed, only 557 (4.69 per cent) were due to N. meningitidis serogroup A. There was no correlation observed between the nasopharyngeal meningococcal carriage in the healthy population with the disease prevalence. There was no seasonal variation in nasopharyngeal carriage though upsurge in the number of meningococcal meningitis cases was noticed from January to April.     

Antibodies against IgA1 protease are stimulated both by clinical disease and asymptomatic carriage of serogroup A Neisseria meningitidis.

IgA1 protease was purified from a strain of serogroup A Neisseria meningitidis subgroup IV-1, representative of bacteria that caused an epidemic of meningococcal meningitis in The Gambia in 1982-1983. ELISAs and immunoblot assays were done using this protease as antigen with paired acute- and convalescent-phase sera from patients from that epidemic and from one in Finland caused by other serogroup A meningococci. Paired sera were also tested from healthy Gambians who were persistent nasopharyngeal carriers, persistent noncarriers, or persons who became carriers after the first serum sample was taken. The results correlated well between the two methods: Antibodies were stimulated by disease or acquisition of carriage, and they remained at a constant level upon continued carriage.     

Predictors of immunity after a major serogroup W-135 meningococcal disease epidemic, Burkina Faso, 2002

BACKGROUND: The African meningitis belt undergoes recurrent epidemics caused by Neisseria meningitidis serogroup A. During 2002, Burkina Faso documented the first large serogroup W-135 (NmW-135) meningococcal disease epidemic. To understand the emergence of NmW-135, we investigated meningococcal carriage and immunity. METHODS: Immediately after Burkina Faso's epidemic, we conducted a cross-sectional survey of meningococcal carriage and seroprevalence in an epidemic and a nonepidemic district. We identified predictors of elevated NmW-135 serum bactericidal activity (SBA), a functional correlate of protection, using multivariate logistic regression. RESULTS: The NmW-135 carriage rate was 25.2% in the epidemic district and 3.4% in the nonepidemic district (P<.0001). Compared with residents of the nonepidemic district, those of the epidemic district had higher geometric mean titers of NmW-135 SBA (P<.0001). NmW-135 SBA titers>or=1:8, an estimated protective threshold, were observed in 60.4% and 34.0% of residents of the epidemic and nonepidemic district, respectively (P=.0002). In a multivariate model, current NmW-135 carriage, age, and residence in the epidemic district were independent predictors of having an NmW-135 SBA titer>or=1:8. CONCLUSIONS: Extensive NmW-135 carriage and transmission in the epidemic area caused residents to acquire natural immunity. Serial carriage and seroprevalence surveys could establish the duration of immunity in the population. The persistent circulation of NmW-135 underscores the potential for periodic NmW-135 epidemics in Africa.     

Immunoepidemiology of meningococcal disease in military recruits. I. A model for serogroup independency of epidemic potential as determined by serotyping.

One hundred twenty strains of Neisseria meningitidis were serotyped with use of cross-absorbed rabbit antisera in a bactericidal test. Fifty-eight epidemic strains of serogroup B, C, and Y that occurred simultaneously among military recruits at two basic training centers during a period of epidemic meningococcal disease were compared with 62 strains of serogroups A, B, C, and Y isolated worldwide. Antisera to the six original antigenic factors of the Gold serotyping schema were adequate for typing 94% of strains, including all of the epidemic strains. The array of serotyping factors in the epidemic strains differed from those in the nonepidemic strains. Epidemic strains were almost exclusively of two serotypes, with type CII predominant among strains of groups B and C. Concurrent strains of groups B and C were invariably of the same serotype. A model for the epidemic potential of meningococcal strains, which is based on their serotype and serogroup antigens, and a modification of the original Gold typing schema are presented.     

Epidemiological patterns of meningococcal meningitis in Niger in 2003 and 2004: under the threat of N. meningitidis serogroup W135

Since the Neisseria meningitidis serogroup W135 epidemic in Burkina Faso in 2002, the neighbouring countries dread undergoing outbreaks. Niger has strongly enhanced the microbiological surveillance, especially by adding the polymerase chain reaction (PCR) assay to the national framework of the surveillance system. During the 2003 epidemic season, 8113 clinically suspected cases of meningitis were notified and nine districts of the 42 crossed the epidemic threshold, while during the 2004 season, the number of cases was 3521 and four districts notified epidemics. In 2003 and 2004, serogroup A was identified in most N. meningitidis from cerebrospinal fluid (CSF) specimens (89.7% of 759 and 87.2% of 406, respectively). Although serogroup W135 represented only 8.3% of the meningococcal meningitis in 2003 and 7.9% in 2004, and was not involved in outbreaks, it was widespread in various areas of the country. In the regions that notified epidemics, the proportion of serogroup W135 was tiny while it exceeded 40% in several non-epidemic regions. Despite the wide distribution of W135 serogroup in Niger and the fears expressed in 2001, the threat of a large epidemic caused by N. meningitidis W135 seems to have been averted in Niger so far. There is no clear indication whether this serogroup will play a lasting role in the epidemiology of meningococcal meningitis or not. As early as in the 1990s, a significant but transient increase in the incidence of N. meningitidis serogroup X was observed. Close microbiological surveillance is crucial for monitoring the threat and for identifying at the earliest the serogroups involved in epidemics.     

Chronicle of an outbreak foretold: meningococcal meningitis W135 in Burkina Faso

Burkina Faso lies within the African meningitis belt. Until recently, serogroup A of Neisseria meningitidis was the most common cause of epidemic meningitis in Burkina Faso. However, during the epidemic that started in January 2002, W135 was the predominant serogroup of meningococcus. Vaccine against the W135 serogroup is expensive and in short supply. Strategies to react to a future African epidemic of W135 meningococcal meningitis with a sufficient and affordable supply of vaccine must be put into place now.     

Genotype-specific carriage of Neisseria meningitidis in Georgia counties with hyper- and hyposporadic rates of meningococcal disease

Carriage of Neisseria meningitidis in a Georgia county with hypersporadic incidence of meningococcal disease ("hypersporadic county") and in a county with no cases of meningococcal disease was determined by a cross-sectional pharyngeal culture study of high school students. Among 2730 students from whom culture samples were obtained, meningococcal carriage was 7.7% (140/1818) in the hypersporadic county and 6.1% (56/912) in the comparison county. Carriage rates by serogroup and genetic type (i.e., electrophoretic type [ET]) did not differ significantly between counties, but apartment or mobile home residency was a risk factor for carriage in the hypersporadic county. Although most cases of meningococcal disease in the hypersporadic county were caused by members of the serogroup C ET-37 clonal group, no ET-37 meningococcal isolates were recovered from carriers in this county. However, 38% of all meningococcal isolates recovered from carriers in both counties were members of the serogroup Y ET-508 clonal group, an emerging cause of meningococcal disease in Georgia and throughout the United States during 1996-2001. Shifts in carriage and transmission of meningococcal strains with different pathogenic potential are important determinants of meningococcal disease incidence.     

Carriage of Neisseria species in communities with different rates of meningococcal disease

A single clone, Neisseria meningitidis serogroup C (C:2a:P1.2), was isolated from seven patients during a cluster of cases of meningococcal disease in Ontario in 1989. To determine whether the clone was present in asymptomatic individuals in the same population, pharyngeal swabs were taken from 7% (644 of 9125) of residents who were vaccinated during the outbreak. Rates of isolation of Neisseria species were also compared to those in two other geographical areas which did not have an elevated incidence of meningococcal disease. The rate of carriage of N meningitidis in the asymptomatic individuals sampled was between 1.9% and 5.4%. The clone isolated from patients was not present among the carrier strains as determined by sero- and subtyping and electrophoretic analysis of metabolic enzymes. Age greater than six years was the only factor associated with colonization with N meningitidis.     

Serogroup A Neisseria meningitidis of clone III-1 present in western Norway as early as 1969-73

A clone of serogroup A Neisseria meningitidis recognized by multilocus enzyme electrophoresis and designated as clone III-1, has caused major epidemics of meningococcal disease in various parts of the world since the 1970s. In Norway, serogroup B meningococci have been responsible for an epidemic since the mid-1970s. We have studied a sample of 53 meningococci isolated from patients in western Norway prior to the serogroup B epidemic. 22/35 meningococcal isolates collected 1969-73 represented clone III-1, whereas this clone was not found in the 18 isolates from 1962-68. It has been speculated that the epidemic of meningococcal disease in Finland caused by clone III-1 in 1973-75 had spread from an epidemic in USSR that began in 1969. Our findings demonstrate, however, that the clone III-1 was present in Scandinavia in 1969.     

Neisseria meningitidis W-135 carriage during the Hajj season 2003.

During the 2003 Hajj pilgrimage to Mecca, 344 pilgrims of 29 different nationalities were screened by means of a throat swab to detect Neisseria meningitidis carriage. N. meningitidis was isolated from 11 subjects; 2 were serogroup W-135, 1 serogroup B, and 8 were non-groupable. The results indicate a very low colonization rate for N. meningitidis among the tested cohort, with a predominance of non-groupable strains. These results, combined with a review of the published data, warrant a re-evaluation of current recommendations by the Saudi Ministry of Health for the use of ciprofloxacin for Saudi pilgrims departing at the end of the Hajj season. However, vaccination with the meningococcal quadrivalent vaccine, for all pilgrims, should continue to be recommended. The possibility of new strains arising as a cause of future meningococcal outbreaks should be considered, and annual surveillance may give an early warning.     

Carriage of serogroup W-135, ET-37 meningococci in The Gambia: implications for immunisation policy?

We found high levels of symptomless carriage of a hyperinvasive Neisseria meningitidis strain (electrophoretic type 37 [ET-37], serogroup W-135) during a vaccine trial in Gambian children in 1996. Serogroup C, ET-37 complex meningococci cause 30-40% of meningococcal disease in countries such as the UK, and have a point prevalence of 0.5-1.0%. The recent Haj-associated spread of serogroup W-135, ET-37 complex meningococci, which has been accompanied by numerous secondary cases, might be explained by the apparently raised carriage rates reported here.     

Neisseria meningitidis serogroups A and W-135: carriage and immunity in Burkina Faso, 2003

OBJECTIVES: We sought to describe Neisseria meningitidis immunity and its association with pharyngeal carriage in Burkina Faso, where N. meningitidis serogroup W-135 and serogroup A disease are hyperendemic and most of the population received polysaccharide A/C vaccine during 2002. METHODS: We collected oropharyngeal swab samples from healthy residents of Bobo-Dioulasso (4-14 years old, n=238; 15-29 years old, n=250) monthly during February-June 2003; N. meningitidis isolates were analyzed using polymerase chain reaction and serogrouped using immune sera. Serum samples were collected at the first and last clinic visit and analyzed for anti-A, anti-C, anti-W-135, and anti-Y immunoglobulin G (IgG) concentrations and anti-A and anti-W-135 bactericidal titers. RESULTS: N. meningitidis was carried at least once by 18% of participants; this carriage included strains from serogroups W-135 (5%) and Y and X (both <1%) but not from serogroups A, B, or C. At baseline, the prevalence of putatively protective specific IgG concentrations (> or =2 microg/mL) and bactericidal titers (> or =8) was 85% and 54%, respectively, against serogroup A, and 6% and 22%, respectively, against serogroup W-135. Putatively protective anti-W-135 IgG concentrations and bactericidal titers were of short duration and were not associated with carriage. CONCLUSION: N. meningitidis serogroup W-135 strains did not induce immunity, despite their circulation. Carriage of serogroup A strains was rare despite the hyperendemic incidence of serogroup A meningitis during 2003 in Bobo-Dioulasso. A vaccine that includes serogroup W-135 antigen and eliminates serogroup A carriage is needed for sub-Saharan Africa.     

An epidemic of disease due to serogroup B Neisseria meningitidis in Alabama: report of an investigation and community-wide prophylaxis with a sulfonamide.

An epidemic of disease due to sulfonamide-sensitive serogroup B Neisseria meningitidis occurred in 1975-1976 in southwestern Alabama. Ten cases occurred in a circumscribed area and resulted in an annual attack rate of 20 cases per 100,000 population. None of the cases were in siblings, and none of the patients had had direct contact with each other. A case-control household study suggested that crowding and person-to-person transmission via carriers may have been contributing risk factors. Seven of the patients were from a triracial ethnic group concentrated in a small isolated rural community within the epidemic area. When three additional cases occurred in this community, a program of community-wide prophylaxis was undertaken as an epidemic control measure, and a large portion of the population participated. No serious side effects were reported. Carrier surveys before and after treatment indicated that compliance with the drug regimen was good and that the drug regimen was associated with a sharp reduction in carriage of N. meningitidis. No cases occurred in the treated population in the five months after treatment.     

Molecular characteristics and susceptibility to antibiotics of serogroup A Neisseria meningitidis strains isolated in Senegal in 1999

A total of 22 strains of Neisseria meningitidis isolated from cerebrospinal fluid samples of patients in Dakar, Senegal, in the course of an epidemic of meningococcal meningitis in 1999 were studied. All the strains were serogroup A, serotype 21:P1.9 and belonged to clonal subgroup III-1. The strains were resistant to sulphonamide, but were susceptible to ampicillin, ceftriaxone and chloramphenicol, which are used in the treatment of cerebrospinal meningitis in Senegal.     

Neisseria meningitidis serogroup W-135 carriage among US travelers to the 2001 Hajj

In 2000, a large international outbreak of meningococcal disease caused by Neisseria meningitidis serogroup W-135 was identified among pilgrims returning from the Hajj in Saudi Arabia. To assess ongoing risk, we evaluated N. meningitidis carriage among US travelers to the 2001 Hajj. Of 25 N. meningitidis isolates obtained, 15 (60%) were nongroupable and 8 (32%) were serogroup W-135 when tested by standard slide-agglutination techniques. Two additional nongroupable isolates were characterized as serogroup W-135 when tested by polymerase chain reaction. Nine of 10 serogroup W-135 isolates were indistinguishable from the Hajj-2000 clone. None of the departing, but 9 (1.3%) of the returning, pilgrims carried serogroup W-135 (P=.01); all carriers reported previous vaccination. Carriage of N. meningitidis serogroup W-135 increased significantly in pilgrims returning from the Hajj. Although the risk of disease to pilgrims appears to be low, the risk of spread to others of this pathogenic strain remains a concern.     

Characteristics of serogroup A Neisseria meningitidis responsible for an epidemic in Ethiopia, 1988-89

In September 1988, an epidemic of meningococcal disease started in Ethiopia. 21 Neisseria meningitidis isolates recovered from patients in Addis Ababa and towns 200 km south of the capital were characterized by serogrouping, serotyping, testing of susceptibility to antibiotics, restriction endonuclease fingerprinting, and multilocus enzyme electrophoresis. The 21 isolates were essentially homogeneous for all properties tested and belonged to clone III-1 of serogroup A N. meningitidis, which was also responsible for the epidemics in Saudi Arabia in 1987 and in Sudan and Chad in 1988.     

Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China

ABSTRACT: BACKGROUND: Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000--2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15--24 years, infection with serogroup C, and meningococcemia. CONCLUSIONS: The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.     

Carriage of Neisseria meningitidis in a semi-isolated arctic community.

The carriage of Neisseria meningitidis was examined in the Norwegian population of Svalbard (1150 persons) after a fatal case of meningococcal septicaemia. The overall carrier rate was 39.0%. The rate was highest among males (47.8%), with a maximum of 63.4% in the age group 15-24 years. The carrier rate was low among children aged 3 to 15 years (6.5%). Children below 3 years were frequent meningococcal carriers, however (37.5%). Sulphonamide-resistant strains were often found, 22.6% of the total material being resistant. Group B was the most frequent serogroup, and accounted for 44.5% of the isolated strains. Non-groupable strains were second in frequency (23.8%), followed by group Y (15.8%). Only a few strains belonged to the serogroups A, C, X and Z. N. lactamica was isolated from 26.9% of children below 15 years, but seldom in older age groups.     

Outbreaks of serogroup X meningococcal meningitis in Niger 1995-2000

In the African meningitis belt, the recurrent meningococcal meningitis epidemics are generally caused by serogroup A. In the past 20 years, other serogroups have been detected, such as X or W135, which have caused sporadic cases or clusters. We report here 134 meningitis cases caused by Neisseria meningitidis serogroup X that occurred in Niamey between 1995 and 2000. They represented 3.91% of the meningococcal isolates from all CSF samples, whereas 94.4% were of serogroup A. Meningococcal meningitis cases were detected using the framework of the routine surveillance system for reportable diseases organized by the Ministry of Public Health of Niger. The strains were isolated and determined by the reference laboratory for meningitis in Niamey (CERMES) and further typed at the WHO collaborating center of the Pharo in Marseille and at the National Reference Center for the Meningococci at the Institut Pasteur. Reference laboratories in Marseille and Paris characterized 47 isolates having the antigenic formula (serogroup:serotype:sero-subtype) X:NT:P1.5. Meningitis cases due to meningococcus serogroup X did not present any clinical or epidemiological differences to those due to serogroup A. The seasonal incidence was classical; 93.3% of the cases were recorded during the dry season. The mean age of patients was 9.2 years (+/- 6 years). The sex ratio M/F was 1.3. Case fatality rate was 11.9% without any difference related to age or sex. The increasing incidence of the serogroup X was not related to the decrease of serogroup A, but seemed cyclic, and evolved independently of the recurrence of both serogroups A and C.     

Genetic analysis of meningococci carried by children and young adults

BACKGROUND: Neisseria meningitidis is a diverse commensal bacterium that occasionally causes severe invasive disease. The relationship between meningococcal genotype and capsular polysaccharide, the principal virulence factor and vaccine component, was investigated in carried meningococci isolated from 8000 children and young adults in Bavaria, Germany. METHODS: Of the 830 meningococci isolated (carriage rate, 10.4%) by microbiological techniques, 822 were characterized by serogrouping, multilocus sequence typing, and genetic analysis of the capsule region. Statistical and population genetic analyses were applied to these data. RESULTS: The rapid increase in carriage rates with age of carrier, the low prevalence of hyperinvasive meningococci, and the relative prevalence of the 4 disease-associated serogroups were consistent with earlier observations. There was no genetic structuring of the meningococcal population by age of carrier or sampling location; however, there was significant geographic structuring of the meningococci isolated in civil, but not military, institutions. The rate of capsule gene expression did not vary with age of carrier or meningococcal genotype, except for serogroup C, for which increased expression was associated with ST-11 (formerly ET-37) complex meningococci. CONCLUSIONS: Serogroup C capsule expression during carriage may contribute to the invasive character of ST-11 complex meningococci and to the high efficacy of meningococcal serogroup C conjugate polysaccharide vaccine.