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PubMed1969

Human immunity to the meningococcus. V. The effect of immunization with meningococcal group C polysaccharide on the carrier state.

Purified meningococcal polysaccharides were administered to army recruits. No adverse reactions were observed in 145 men who received group C polysaccharide, and in 53 men who were injected with group A polysaccharide. Hemagglutinating and bactericidal activity developed in the sera of all individuals with the exception of two recruits injected with A polysaccharide. During the 6 wk period of observation, the proportion of unvaccinated recruits who acquired group C meningococci in the three companies studied was 38, 42, and 69 per cent. A significantly lower proportion of the individuals vaccinated with group C polysaccharide acquired group C meningococci; 4.6, 24, and 31 per cent respectively.

Adult↗

PubMed2003

Effect of infant immunisation with meningococcus serogroup C-CRM(197) conjugate vaccine on diphtheria immunity and reactogenicity in pre-school aged children.

The majority of Men C conjugate vaccines given in the UK use CRM(197), a mutant diphtheria toxoid, as their protein carrier. We studied the effects of prior immunisation with Men C-CRM(197) conjugate vaccine on immunity to diphtheria in 193 children before and after a booster dose of Men C at 4 years. Baseline diphtheria antibodies were higher in children given four previous doses of Men C (P<0.0001) and tended to be higher following boosting in those who had received three or four doses. This enhanced immunity was not associated with increased reactogenicity.

Child, Preschool↗

PubMed2004

Future vaccine development at NICHD.

Using published data and the results of our studies, we hypothesized that a critical level of serum IgG antibodies to the surface structures of invasive pathogens (capsular polysaccharides of Haemophilus influenzae type b, pneumococcus, meningococcus, Salmonella typhi, Escherichia coli, and Staphylococcus aureus, the O-specific polysaccharide LPS domain of the LPS of Shigella, non-typhoidal Salmonella, and E. coli, and the capsular polypeptide of Bacillus anthraces) confer immunity to these pathogens. Covalent attachment to a protein increases their immunogenicity and bestows T-cell properties to these antigens. We have also shown that a critical level of serum IgG antibodies to pertussis toxin alone induces immunity on both an individual and on a community basis (herd immunity) to Bordetella pertussis. It is likely that all the above conjugates and pertussis toxoid will be incorporated into vaccines for routine infant immunization.

Bacterial Infections↗

PubMed2002

Guidelines for public health management of meningococcal disease in the UK.

Following changes in the epidemiology of meningococcal disease, the advent of new vaccines, and with new evidence on risk and control measures, the Public Health Laboratory Service Meningococcus Forum set up a Working Group to review the guidance for control measures in the UK. This review is based on available evidence, and recommendations are graded according to the level of evidence on which they are based. These guidelines cover pre-admission management, investigation of suspected cases, the role of public health, public health action after a single case, prophylaxis in healthcare settings, and management of clusters. Detailed revised recommendations are presented on the use of antibiotics before admission to hospital, the rationale and indications for chemoprophylaxis, and the use of new vaccines. Links to relevant websites are included.

Anti-Bacterial Agents↗

PubMed1991

[Purulent meningitis due to flavobacterium meningosepticum in Cameroonian children].

Following a number of reports of purulent CSF specimens positive for Flavobacterium meningosepticum in pediatric patients in Yaoundé, a prospective study was carried out in the Department of Pediatrics of the Central Yaoundé Hospital from December 1988 through December 1989. The goals of this study were to determine the incidence of Flavobacterium meningosepticum among infants and children with purulent meningitis, to discover the origin of this pathogen, and to examine its susceptibility to antimicrobial agents. Flavobacterium meningosepticum (18.4% of cases) was second by order of incidence, after pneumococci (50%). Incidences were low for the other pathogens usually described in purulent meningitis (H. influenzae, meningococcus...). All the pneumococcus strains recovered were susceptible to ampicillin. In contrast, 21.43% of strains of Flavobacterium meningosepticum were resistant to both ampicillin and chloramphenicol (the combination currently used as first line therapy in the Department), and 14.25% of strains were resistant to cefotaxime. The origin of the Flavobacterium meningosepticum strains found remains to be discovered. The low incidence of H. influenzae deserves to be reevaluated over the next few years.

Adolescent↗

PubMed2001

Preventing secondary meningococcal disease in health care workers: recommendations of a working group of the PHLS meningococcus forum.

Based on new data on the risk of secondary meningococcal disease in health care workers, a review of published cases and an assessment of the available evidence, a change to the recommendations for giving chemoprophylaxis to health care workers in England and Wales is proposed. Previous guidance recommended prophylaxis only for those who had given mouth to mouth resuscitation. Chemoprophylaxis is now recommended for health care workers whose mouth or nose has been directly and heavily exposed to respiratory droplets/secretions from a case of meningococcal disease around the time of hospital admission. Wearing surgical face masks is encouraged to reduce risk of exposure.

Antibiotic Prophylaxis↗

PubMed2006

Suitable age for nasal reconstruction after subtotal amputation in a child, with respect to a case involving purpura fulminans.

The authors report a case of nasal reconstruction in a 5-year-old boy who had undergone subtotal amputation of the nose 8 months before in the context of meningococcus-induced purpura fulminans. Two-step surgery involved implantation of a forehead expansion graft preliminary to use of a contralateral forehead flap to cover a cartilaginous graft from the concha that reconstituted the ala nasi, columella, and septum. At 1 year of follow-up, the results were considered quite satisfactory esthetically and psychologically beneficial. Nasal amputation in the child is infrequent, and the procedure is not clearly defined. Early reconstruction certainly improves the child's life and social integration. The major risk is unsatisfactory growth of the reconstructed nose, which may persuade some surgeons to postpone the operation.

Age Factors↗

PubMed2002

Pre-hospital parenteral antibiotic treatment of meningococcal disease and case fatality: a Danish population-based cohort study.

OBJECTIVES: Studies about the efficiency of pre-hospital antibiotic treatment of meningococcal disease are conflicting. We examined the case fatality rate in patients with meningococcal disease treated with pre-hospital antibiotics. METHODS: A cohort study of 534 patients hospitalized with meningococcal disease from two Danish counties. Clinical data were obtained from referral letters from general practitioners and hospital records. Complete follow-up for all patient until death or discharge. RESULTS: Seventy-seven patients (16% of the patients seen by a general practitioner) received parenteral antibiotics before hospital admission; 9 (12%) of them died. Of 402 patients who did not receive pre-hospital parenteral antibiotics, 26 (7%) died. The overall risk of case fatality among antibiotic-treated patients was increased with adjusted odds ratio (OR) = 2.4 (95% CI, 1.0-5.6). Meningococcus serogroup B was associated with increased case fatality in patients who received pre-hospital parenteral antibiotics (OR = 2.6; 95% CI, 0.8-8.3) in contrast to other serogroups. In Aarhus County there were no deaths in patients who received pre-hospital parenteral antibiotics, but in North Jutland County the case fatality was high (OR = 2.9; 95% CI, 1.2-6.8). CONCLUSIONS: The efficiency of pre-hospital parenteral antibiotic treatment seems to be dependent on hospital care and may vary with the serogroup.

Adolescent↗

PubMed2001

Confirmation of meningococcal disease by urinary antigen testing.

The meningococcus is an important cause of morbidity and mortality and a rapid laboratory diagnosis is required through accurate, non-culture-based methods. Body fluids that are easily obtainable are preferred for this route of diagnosis and urine is the specimen of choice as it can be obtained non-invasively. Urine samples were tested from patients with suspected meningococcal disease and tested by latex agglutination and PCR. It was shown that urinary PCR is not useful for the laboratory confirmation of MD but latex agglutination testing may be useful in certain settings prior to confirmatory testing by a reference laboratory.

Antigens, Bacterial↗

PubMed2001

Vaccines against meningococcal disease: current and future technologies.

Development of the meningococcal serogroup C conjugate vaccine and its national implementation in the UK has been a major breakthrough in the prevention of meningococcal disease. New technologies are increasing the likelihood that research towards a vaccine against group B meningococcus will be successful. This review covers the recent development of vaccines against meningococcal disease and examines future vaccine candidates. The development of meningococcal polysaccharide vaccines was based on the virulence of the bacterial capsule components. The immunogenicity of these vaccines has been improved by covalent linkage to proteins in the new meningococcal C conjugate vaccines. However, the most promising developments for serogroup B disease have stemmed from other virulence determinants such as outer membrane proteins (OMPs) and lipopolysaccharides (LPS). New genome sequencing technology promises a way forward to developing a broadly cross-protective vaccine for this important pathogen.

Adolescent↗

PubMed1991

Meningococcal carriage in close contacts of cases.

Between 1 October 1986 and 31 March 1987, 55 cases of meningococcal disease were identified in the South-West of England, an attack rate of 1.54 per 100,000 during the study period. Antibiotics used in the treatment of the disease successfully eliminated nasopharyngeal carriage of meningococci in 13 out of 14 cases without use of rifampicin. The overall meningococcal carriage rate in 384 close contacts was 18.2% and the carriage rate of strains indistinguishable from the associated case strain was 11.1%. The carriage rate of indistinguishable strains in household contacts (16.0%) was higher than the carriage rate in contacts living at other addresses (7.0%, P less than 0.05). A 2-day course of rifampicin successfully eradicated meningococci from 46 (98%) of 47 colonized contacts. In one third of cases groupable meningococci were isolated from at least one household contact; 92% of these isolates were of the same serogroup as the associated case strain. When a meningococcus is not isolated from a deep site in a clinical case of meningococcal disease, culture of serogroup A or C strains from nasopharyngeal swabs of the case or of household contacts is an indication that the close contact group should be offered meningococcal A + C vaccine in addition to chemoprophylaxis. The failure in this and other studies to isolate meningococci from any household contact in the majority of cases may be due either to the relative insensitivity of nasopharyngeal swabbing in detecting meningococcal carriage or to the acquisition of meningococci by most index cases from sources outside the household.

Adolescent↗

PubMedDate not supplied

Use of bacterial vaccines for prevention of pneumococcal and meningococcal disease in the day care setting.

The pneumococcus causes severe disease, including meningitis and bacteremia, in children of day care age. It is also a frequent cause of otitis media. Unfortunately, the currently available pneumococcal polysaccharide vaccine has not been efficacious in children under 24 months old; research is currently underway on methods for increasing immunogenicity in young children. The meningococcus is a rare cause of meningitis in day care aged children, but children in day care are likely to be at increased risk of secondary disease if a case occurs in a center. The currently available polysaccharide meningococcal vaccine is poorly immunogenic in children younger than two and does not include the group B polysaccharide, which is responsible for 70% of disease in children younger than five years. Therefore, chemoprophylaxis with rifampin is recommended for decreasing the risk of secondary spread. When a group B meningococcal vaccine immunogenic in young children becomes available, vaccination will be indicated for all children in day care.

Age Factors↗

PubMed2001

Introduction of an automated service for the laboratory confirmation of meningococcal disease in Scotland.

The Scottish Meningococcus and Pneumococcus Reference Laboratory provides a national service for the laboratory confirmation of meningococcal and pneumococcal disease in Scotland. The main tests used for the laboratory confirmation of meningococcal disease are culture, the polymerase chain reaction (PCR), antibody testing, and more recently DNA sequencing. This paper describes the automation of PCR for the laboratory confirmation of meningococcal disease and the typing of meningococcal isolates using DNA sequencing. Both methods have been automated using a robotic liquid handler and automated DNA sequencer. These methods, along with standard culture phenotyping and antibody testing, provide Scotland with an excellent service for the confirmation of meningococcal disease.

Automation↗

PubMed2001

Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment.

OBJECTIVE: Despite the lack of evidence defining a time interval during which cerebrospinal fluid (CSF) culture yield will not be affected by previous antibiotic therapy, recent publications cite a "minimum window" of 2 to 3 hours for recovery of bacterial pathogens after parenteral antibiotic administration. We conducted a retrospective review of children with bacterial meningitis to describe the rate at which parenteral antibiotic pretreatment sterilizes CSF cultures. METHODS: The medical records of pediatric patients who were discharged from a tertiary children's hospital during a 5-year period with the final diagnosis of bacterial meningitis or suspected bacterial meningitis were reviewed. The decay in yield of CSF cultures over time was evaluated in patients with lumbar punctures (LP) delayed until after initiation of parenteral antibiotics and in patients with serial LPs before and after initiation of parenteral antibiotics. RESULTS: The pathogens that infected the 128 study patients were Streptococcus pneumoniae (49), Neisseria meningitidis (37), group B Streptococcus (21), Haemophilus influenzae (8), other organisms (11), and undetermined (3). Thirty-nine patients (30%) had first LPs after initiation of parenteral antibiotics, and 55 (43%) had serial LPs before and after initiation of parenteral antibiotics. After >/=50 mg/kg of a third-generation cephalosporin, 3 of 9 LPs in meningococcal meningitis were sterile within 1 hour, occurring as early as 15 minutes, and all were sterile by 2 hours. With pneumococcal disease, the first negative CSF culture occurred at 4.3 hours, with 5 of 7 cultures negative from 4 to 10 hours after initiation of parenteral antibiotics. Reduced susceptibility to beta-lactam antibiotics occurred in 11 of 46 pneumococcal isolates. Group B streptococcal cultures were positive through the first 8 hours after parenteral antibiotics. Blood cultures were positive in 74% of cases without pretreatment and in 57% to 68% of cases with negative CSF cultures. CONCLUSIONS: The temptation to initiate antimicrobial therapy may override the principle of obtaining adequate pretreatment culture material. The present study demonstrates that CSF sterilization may occur more rapidly after initiation of parenteral antibiotics than previously suggested, with complete sterilization of meningococcus within 2 hours and the beginning of sterilization of pneumococcus by 4 hours into therapy. Lack of adequate culture material may result in inability to tailor therapy to antimicrobial susceptibility or in unnecessarily prolonged treatment if the clinical presentation and laboratory data cannot exclude the possibility of bacterial meningitis.

Adolescent↗

PubMedDate not supplied

[Meningococcus B serosubtypes causing invasive disease in Cantabria [Spain] and agreement with the Cuban vaccine strain].

OBJECTIVE: To determine the serosubtypes of meningococcus B causing invasive disease in Cantabria and the percentage of agreement with the Cuban vaccine strain, VA-MENGOC-BC. METHODS: We performed a retrospective review of all cases of invasive disease due to meningococcus B declared through the Diseases of Mandatory Reporting System between 1st January 1998 and 28th February 2003. The bacteriological isolates of the "Marqués de Valdecilla" University Hospital, and the serosubtyping performed in the Majadahonda reference laboratory (Madrid, Spain) were also analyzed. RESULTS: Of the 117 declared cases, serosubtype was identified in 79 (67.5%). The agreement with the Cuban vaccine strain was 67%, 71% and 76% in the age groups of newborn to 19 years, 18 months to 19 years, and 4 to 19 years, respectively. When strains with cross-protection were included, these percentages increased to 83%, 83% and 84%, respectively, in the same age groups. CONCLUSIONS: The percentage of agreement between the Cuban vaccine strain and heterologous strains with cross-protection was high. Therefore, this vaccine could be useful in Cantabria.

Bacterial Capsules↗

PubMed1994

Eradication of Haemophilus influenzae type b disease in southern California. Kaiser-UCLA Vaccine Study Group.

OBJECTIVE: To assess the effects of Haemophilus influenzae vaccination of infants. RESEARCH DESIGN: We evaluated H influenzae type b (Hib) disease rates in Los Angeles County, California (population, 9 million; 1983 through 1992), and in the Southern California Kaiser Health Plan (2.5 million enrollees; 1988 through 1992) during the past decade. Cases were obtained through active and passive disease surveillance in the two populations. The following vaccines were used during the study period (1983 through 1992): (1) Hib polysaccharide vaccine (polyribosyl ribitol phosphate) (used from 1985 through 1987 for children 24 through 60 months of age); (2) Hib polysaccharide-diphtheria toxoid conjugate, Hib polysaccharide CRM197 mutant diphtheria toxoid conjugate vaccine, and Hib polysaccharide outer-membrane protein of group B meningococcus conjugate vaccine in older children (1988 through 1990; ages 15 through 60 months); and (3) Hib polysaccharide CRM197 mutant diphtheria toxoid conjugate vaccine and Hib polysaccharide outer-membrane protein of group B meningococcus conjugate vaccine used in infants (1991 through 1992). MEASUREMENTS AND RESULTS: Between 1983 and 1988, the Hib disease incidence in Los Angeles County was unchanged (32.7 to 42.5/100,000 person-years in children younger than 5 years). In 1989 through 1990, before Hib conjugate licensure for infant use, Hib disease rates in all age groups declined. After licensure of Hib vaccines for infants in 1990, there was a further fivefold decrease in infants. More dramatic decreases occurred in the better-immunized Kaiser Health Plan children aged 0 through 60 months (53 cases in 1989, only two cases in 1992). CONCLUSIONS: The Hib disease has been nearly eradicated in a fully immunized population (Kaiser Health Plan), and significant reductions have also occurred in Los Angeles County.

California↗

PubMed1997

PCR-single-stranded confirmational polymorphism analysis for non-culture-based subtyping of meningococcal strains in clinical specimens.

Subspecific typing of clinical meningococcal strains is important in the investigation of outbreaks and for disease surveillance. Serogrouping, typing, and subtyping of strains currently require isolation of a meningococcus from one or more clinical specimens. However, the increasing widespread practice of preadmission administration of parenteral antibiotics has resulted in a decrease in the frequency of positive cultures obtained from blood and cerebrospinal fluid. Confirmation of meningococcal disease can be obtained by meningococcus-specific PCR from both cerebrospinal fluid (H. Ni et al., Lancet 340:1432-1434, 1992) and peripheral blood (J. Newcombe et al., J. Clin. Microbiol. 34:1637-1640, 1996) specimens. However, current PCR protocols do not yield epidemiologically useful typing information. We report here the use of PCR-single-stranded confirmational polymorphism (PCR-SSCP) analysis to amplify and type meningococcal DNA present in clinical specimens. PCR-SSCP analysis with the VR1 region of the Neisseria meningitidis porA gene as the target produced unique banding patterns for each serosubtype. Direct PCR-SSCP of clinical specimens can therefore provide typing data that can be used to investigate the epidemiology of clusters of cases and outbreaks and for disease surveillance in situations in which culture of patient specimens proves negative.

Bacterial Typing Techniques↗

PubMed1996

Safety and immunogenicity of a serogroups A/C Neisseria meningitidis oligosaccharide-protein conjugate vaccine in young children. A randomized controlled trial.

OBJECTIVE: To assess the safety and immunogenicity of a bivalent serogroups A/C meningococcal oligosaccharide-protein conjugate vaccine compared with the licensed meningococcal polysaccharide vaccine. DESIGN: Randomized controlled trial. STUDY POPULATION: Ninety healthy 18- to 24-month-old children who were seen at a southern California Kaiser Permanente clinic. INTERVENTIONS: Vaccination with either the meningococcal conjugate vaccine (at 1 of 2 dosages) or the polysaccharide vaccine, with 2 doses given 2 months apart. MAIN OUTCOME MEASUREMENTS: Immune response to each vaccine dose as determined by measurement of serogroup-specific total antibodies by enzyme-linked immunosorbent assay (ELISA) and by assessment of serum bactericidal activity. RESULTS: Both vaccines appeared to be safe, and nearly all children responded with greater than 4-fold increases in antibody levels. The 2 dosages of the conjugate vaccine induced similar antibody responses; therefore, the data for the 2 conjugate vaccine groups were combined. Following 2 doses, ELISA antibody levels against group C meningococcus were significantly higher in conjugate vaccine recipients than in polysaccharide vaccine recipients (16.66 microg/mL vs. 8.31 microgm/mL; P<.001), but antibody levels against group A were not significantly different 22.75 microg/mL vs 21.24 microg/mL; P=.70). The serum bactericidal assays showed striking differences between the conjugate and polysaccharide vaccine groups. Geometric mean serum bactericidal titers were significantly higher in conjugate vaccine recipients (755.6 vs 37.6 for group A, P<.001; 3197.9 vs 11.4 for group C, P<.001). CONCLUSIONS: The immune response induced by this meningococcal oligosaccharide-protein conjugate vaccine was qualitatively different from that induced by the polysaccharide vaccine, and the antibodies it elicited provided greater functional activity.

Antibodies, Bacterial↗