Outbreak Of Meningococcal Disease Research Articles

In vitro activities of ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, and rifampin against fully susceptible and moderately penicillin-resistant Neisseria meningitidis

Moderately penicillin-resistant Neisseria meningitidis was responsible for an outbreak of meningococcal disease in Saskatoon, Saskatchewan, Canada in 1993. We tested fully susceptible and moderately resistant strains of N. meningitidis against ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, penicillin, and rifampin. Eighteen percent of the isolates were moderately resistant to penicillin (MIC > or = 0.06 microgram/ml) whereas susceptibility was 100% for the other agents tested.

Neisseria meningitidis with decreased susceptibility to penicillin in Saskatchewan, Canada.

Moderately penicillin-resistant Neisseria meningitidis is rare in North America. We report an outbreak of meningococcal disease in Saskatoon, Saskatchewan, Canada, with serogroup C N. meningitidis. The MICs of penicillin ranged from 0.12 to 0.25 micrograms/ml, and all isolates showing decreased susceptibility had identical genomic fingerprints when they were compared by pulsed-field gel electrophoresis. Our data indicate that N. meningitidis that is moderately resistant to penicillin is prevalent in Saskatchewan, Canada.

Relationship between parental occupation and children's oropharyngeal colonization with Neisseria meningitidis

We explored, during an outbreak of meningococcal disease, whether children of parents with workplace exposure to children were at increased risk of oropharyngeal colonization with Neisseria meningitidis. In comparison with children of parents without workplace exposure to children, the risk of colonization was not increased (odds ratio 0 = 1.62; 95% confidence interval, 0.56 to 4.72). Therefore a parent's occupation does not appear to increase the risk of their children's colonization with N. meningitidis. (J PEDIATR 1995;126:937-9)

Emergence of a new virulent clone within the electrophoretic type 5 complex of serogroup B meningococci in Norway

An increase in B:15:P1.12 meningococci among isolates from patients with Neisseria meningitidis infection in Norway in recent years led to further characterization of such strains. Between 1987 and 1992, B:15:P1.12 strains constituted 9.8% (24 strains) of B:15 isolates. The B:15:P1.12 strains belonged to the electrophoretic type 5 (ET-5) complex, but 17 (71%) strains were a new clone (ET-5c) not found elsewhere in the world. All but one strain of ET-5c were responsible for a localized outbreak of systemic meningococcal disease in western Norway. A novel monoclonal antibody (202,G-12), developed against the unknown variable region 2 on the class 1 protein of one of these strains, bound to 19 of the 15:P1.12 strains, 4 strains bound the subtype P1.13 reference monoclonal antibody MN24H10.75, and the remaining strain showed no reaction. Sequencing of porA genes demonstrated a series of nine threonine residues in the deduced variable region 2 of the latter strain, while four and five threonine residues were found in the corresponding regions of strains reacting with the monoclonal antibodies 202,G-12 and MN24H10.75, respectively. Epitope mapping with synthetic peptides showed that 202,G-12 bound to a sequence of 11 amino acids which included the four threonine residues specific for subtype P1.13a. Immunoglobulin G antibodies against the P1.7,16 subtype protein, induced in volunteers after vaccination with the Norwegian meningococcal vaccine, did not cross-react on immunoblots with the subtype protein of clone ET-5c. Thus, postvaccination class 1 protein antibodies, assumed to be protective, may not be effective against infection with the new clone.

Undertaking mass meningococcal vaccination: criteria and experiences

An outbreak of meningococcal disease in the Northern Sydney Area provided an opportunity for the Area's Public Health Unit (PHU) to review the criteria for undertaking a mass vaccination program and to relate its experiences to other public health professionals.

Demonstration of lipooligosaccharide immunotype and capsule as virulence factors for Neisseria meningitidis using an infant mouse intranasal infection model

Using an infant mouse intranasal infection model, we have compared the virulence of 17 epidemiologically related isolates of Neisseria meningitidis associated with an outbreak of meningococcal disease in Gloucestershire, UK, and one germane isolate. The isolates were all of serotype 15 subtype P1:7, 16 and were identical by restriction fragment length polymorphism analysis, but differed in either (i) whether they were isolated from a case or a carrier, (ii) the presence or absence of group B capsule, or (iii) their lipooligosaccharide (LOS) immunotype. The results indicate that capsule is a major virulence determinant and is required for colonization and hence for invasion. In addition, the LOS L3,7,9 immunotype, when compared to the L1,8,10 immunotype, is a secondary virulence factor which enhances colonization of nasal passages and invasion of the blood stream by both case and carrier isolates. Two case isolates which were unusual in possessing the L1,8,10 immunotype, established invasive infection, but this was associated with a switch to the L3,7,9 immunotype. The results confirm that LOS is a virulence factor for N. meningitidis and that immunotype L3,7,9 is associated with invasive disease.

Characterization of Neisseria meningitidis by polymerase chain reaction and restriction endonuclease digestion of the porA gene.

Subtype classification based on the use of monoclonal antibodies to the class 1 outer membrane protein combined with techniques such as multilocus enzyme electrophoresis remains the standard method of characterizing isolates during outbreaks of invasive meningococcal disease. We developed a rapid typing method based on the restriction fragment length polymorphisms (RFLPs) within the polymerase chain reaction (PCR) product of the porA gene, which encodes the class 1 outer membrane protein, reflecting genotypic rather than phenotypic variability between strains. Forty-five isolates of invasive Neisseria meningitidis obtained from October 1990 to April 1992 were studied after randomization and coding. Included among these were isolates from a local outbreak that resulted in a mass vaccination program. PCR amplification for each isolate was followed by restriction digestion with the following enzymes in the indicated sequence: HaeIII, RsaI, HinfI, HpaII, and AluI. Eighteen different patterns were demonstrated on the basis of RFLPs, whereas only seven groups were identified after standard subtyping. The most common isolate identified by serosubtyping was serogroup C, serotype 2a, subtype P1.2 (C:2a:P1.2) (38%). Thirteen (76%) of these group C isolates shared a common RFLP pattern after digestion with the five restriction enzymes. We were able to further differentiate strains of C:2a:P1.2 with electrophoretic type 5 from electrophoretic types 1, 9, and 15 that occurred during an apparent outbreak. We were also able to characterize 15 isolates (33%) which could not be subtyped with monoclonal antibodies. Our method offers a convenient alternative to standard subtyping procedures and is particularly useful in outbreak situations in which rapid characterization of N. meningitidis is essential so that rational public health policy regarding preventative measures can be formulated.

Use of single-dose ofloxacin to eradicate tonsillopharyngeal carriage of Neisseria meningitidis

After an outbreak of three cases of serogroup B meningococcal disease at a Norwegian college, 84 of 392 (21%) subjects were tonsillopharyngeal carriers of Neisseria meningitidis. To eradicate meningococcal carriage, 80 volunteers received a single dose of 400 mg of ofloxacin. Three days after treatment, all 75 evaluable volunteers were culture negative for N. meningitidis, and after 7 days none carried the strain that they carried initially, as judged by DNA fingerprinting. A single dose of ofloxacin was found to be 97.2% effective in eradicating carriage of N. meningitidis for a period of 33 days. The carriage acquisition rate among treated students was four times higher than that among nontreated noncarriers (P = 0.02). After ofloxacin treatment, no case of meningococcal disease occurred for 6 months. Ofloxacin may thus prevent the outbreak and spread of meningococcal disease.

Identification and characterization of a novel insertion sequence, IS1106, downstream of the porA gene in B15 Neisseria meningitidis.

Examination of Neisseria meningitidis strains associated with endemic meningococcal disease demonstrated differences in the number of copies of a repetitive sequence. Characterization of a copy of this repetitive sequence present in B15 strains has revealed the presence of a novel insertion sequence (IS1106) located within a complex repetitive region downstream of the gene for the major surface antigen (porA). IS1106 has a length of 1137 bp and is flanked by 36bp inverted repeats. Two open reading frames (ORF1 and ORF2) are present in opposite strands in codon-codon register with ORF2 entirely located within ORF1. The predicted protein from ORF1 demonstrates homology with the 5A protein of IS5 (Kroger and Hobom, 1982). Strains from two independent outbreaks of B15 meningococcal disease in the UK were found to contain the same genomic deletion removing a copy of IS1106 downstream of the porA gene.

Influenza A and meningococcal disease

There are several anecdotal accounts of the association between outbreaks of influenza and meningococcal disease. The exceptional increase in the number of cases of meningococcal infection 2 weeks after an influenza A outbreak in England and Wales during November and December, 1989, provided an opportunity to investigate the relation between the two events. Patients with meningococcal disease in December, 1989, were more likely than age-matched controls to show serological evidence of recent influenza A infection (odds ratio 3·9, 95% Cl 1·2-13·9). The most likely explanation for the association is immune suppression induced by influenza A, though a lowering of mucosal resistance to meningococcal invasion may also be a factor. Public health authorities should be aware of the association and should be prepared to alert medical practitioners and the public to the increased risk of meningococcal disease when influenza A outbreaks occur.

A Cluster of Meningococcal Disease on a School Bus Following Epidemic Influenza

An outbreak of meningococcal disease among children on a school bus offered the opportunity to study a proposed association between this infection and preceding influenza infection. Five students who rode the bus became ill with invasive group C meningococcus. Transmission was limited to the bus; there was no evidence for school transmission. All five students reported influenza-like symptoms within several weeks before the development of meningococcal disease. School absenteeism, principally due to upper respiratory tract illness, was higher during the 3 weeks before the outbreak of meningococcal disease than during any period in the preceding 3 1/2 years, suggesting an unusually severe outbreak of respiratory illness. A case-control study comparing students with and without influenza symptoms revealed that the outbreak of respiratory disease was due to B/Ann Arbor/1/86 influenza (geometric mean titers, 86 for 80 patients and 33 for 47 controls [P = .0007]). These data add to the evidence suggesting that influenza respiratory infection predisposes to meningococcal disease.

Group A meningococcal disease in England associated with the Haj

An outbreak of group A meningococcal infection amongst the Muslim population in England followed the outbreak of meningococcal disease associated with the 1987 Haj to Mecca. There were 18 primary cases amongst pilgrims returning from Mecca and 15 subsequent cases among Muslims over the following 19 months. The meningococcal strains were shown to be of the same clone as strains from the Mecca outbreak by possession of an outer membrane protein PI.9. Strains of this group A clone (A III-I) had only rarely been encountered in England before this outbreak.

Secretor status, smoking and carriage ofNeisseria meningitidis

A survey of ABO blood groups, secretor status and smoking habits among 389 students and staff of a school in which there was an outbreak of meningococcal disease found no difference in the distribution of the ABO blood groups but a significantly higher proportion of non-secretors (37.6%) in the population examined compared with that reported for previous surveys of the neighbouring population in Glasgow (26.2%) (P less than 0.0005). There was also a significantly higher proportion of non-secretors among carriers of meningococci (47%) compared with non-carriers (32%). Increased carriage of meningococci among non-secretors might contribute to the increased susceptibility of individuals with this genetic characteristic to meningococcal disease observed in previous studies. Although passive exposure to cigarette smoke has been associated with meningococcal disease, there was no association between passive smoking and carriage. There was, however, a significant association between active smoking and carriage.

Use of DNA fingerprinting in an epidemiologic study of outbreak-specific and non-specific strains of group C Neisseria meningitidis

DNA fingerprints of nine group C isolates of Neisseria meningitidis were obtained by digestion with three restriction endonucleases, BamHI, EcoRI, and HindIII. Identical restriction profiles were displayed by five strains isolated from two patients and three contacts during a localized outbreak of meningococcal disease in the area served by our laboratory. A slight difference, appreciable only in the fingerprints obtained with EcoRI, was observed between these isolates and a sixth one isolated from a clinical case occurring in the same area one year later. In contrast, three additional strains, recently isolated from patients in separate areas in Italy, gave restriction profiles differing strikingly from one another and from those produced by the strains isolated in our area.

An outbreak of meningococcal disease in Auckland, New Zealand.

A large epidemic of disease caused by Group A sulfonamide-resistant Neisseria meningitidis has been occurring in Auckland, New Zealand, from June, 1985, and peaking in October, 1985 (spring), and June, 1986 (winter). By the end of 1986 an overall attack rate of 8.3 cases/100,000 total population per year had been calculated. The attack rate in children younger than 15 years was 30.4/100,000/year and the highest rate occurred in children younger than 5 years: all Auckland 68.8/100,000/year; South and Central Auckland 98.7/100,000/year. Seventy-nine percent of cases younger than 15 years of age occurred in 30% of the childhood population. The overall case-fatality ratio was 7% with the highest rate (22%) occurring in male children age 1 to 2 years. An outbreak in an industrialized country of an infectious disease usually seen in developing countries calls for investigation of living conditions and other sociodemographic factors in the population affected. Specific action in the form of a vaccination program particularly targeted to those at risk was planned and implemented before the winter of 1987.

Group A Meningococcal Carriage in Travelers Returning From Saudi Arabia

In August 1987, an outbreak of group A meningococcal meningitis occurred during the annual pilgrimage to Mecca, Saudi Arabia, resulting in an attack rate among American pilgrims of 640 per 100,000. To determine risk factors for carriage, throat cultures were taken from passengers arriving on four consecutive flights from Saudi Arabia to the United States. Pilgrims were more likely to be group A meningococcal carriers than were nonpilgrims (relative risk, 11.1; 95% confidence interval, 3.7 to 33.1). Smoking, crowding, and meningococcal vaccination were not significantly associated with group A carriage. Pilgrims complaining of recent fever or sore throat, however, were more likely to be group A carriers, consistent with previous reports linking carriage and disease to preceding viral infections. Serogrouping of invasive meningococcal isolates can be used to monitor for indigenous transmission of this unusual strain in the United States, and we recommend routine vaccination of pilgrims to prevent future outbreaks of meningococcal disease.

Group A meningococcal carriage in travelers returning from Saudi Arabia

In August 1987, an outbreak of group A meningococcal meningitis occurred during the annual pilgrimage to Mecca, Saudi Arabia, resulting in an attack rate among American pilgrims of 640 per 100 000. To determine risk factors for carriage, throat cultures were taken from passengers arriving on four consecutive flights from Saudi Arabia to the United States. Pilgrims were more likely to be group A meningococcal carriers than were nonpiligrims (relative risk, 11.1; 95% confidence interval, 3.7 to 33.1). Smoking, crowding, and meningococcal vaccination were not significantly associated with group A carriage. Pilgrims complaining of recent fever or sore throat, however, were more likely to be group A carriers, consistent with previous reports linking carriage and disease to preceding viral infections. Serogrouping of invasive meningococcal isolates can be used to monitor for indigenous transmission of this unusual strain in the United States, and we recommend routine vaccination of pilgrims to prevent future outbreaks of meningococcal disease. (<i>JAMA</i>1988;260:2686-2689)

Meningococcal carriage, meningococcal disease and vaccination

Group A meningococcal carriage rates were determined 6 months before and 6 and 18 months after a mass vaccination campaign with a combined group A and group C meningococcal polysaccharide vaccine in a rural area of The Gambia. During the first pre-vaccination survey, performed during an outbreak of meningococcal disease, the carriage rate was high (16%). The carriage rate remained high during a second survey made 6 months after a vaccination campaign that covered approximately 90% of the study population. A year later very few group A meningococcal carriers were found. Membrane protein patterns of isolates obtained before and after vaccination were similar. We conclude that vaccination had little influence on the carriage rate of group A meningococci but that this was influenced by changes in herd immunity or by other unidentified factors.

An outbreak of meningococcal disease in Stonehouse: planning and execution of a large-scale survey.

In November 1986 a large-scale survey was undertaken in the Gloucestershire town of Stonehouse during an outbreak of meningococcal disease due to group B type 15 subtype P1.16 sulphonamide-resistant strains. There were 15 cases in Stonehouse residents during the 4 years from April 1983, an annual attack rate of 56.5 per 100,000. Four secondary cases occurred despite rifampicin prophylaxis. The objectives of this community survey were to investigate patterns of meningococcal carriage, transmission and immunity and to determine the proportion of non-secretors of blood group antigens in the Stonehouse population and amongst meningococcal carriers. A total of 6237 subjects participated including 75% of the 6635 Stonehouse residents. Over 97% of the participants provided all three of the requested specimens-nasopharyngeal swabs, saliva and blood samples. The co-operation between the many organizations involved in the detailed preliminary planning was instrumental in the success of the survey; in particular the value of effective collaboration between Departments of Community Medicine and Microbiology and of the Public Health Laboratory Service network of laboratories in undertaking investigations of this size and type was clearly demonstrated.

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

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.