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At least 1,225 records · Page 68Linked to original sources
PubMed2006

Clinical and immunologic risk factors for meningococcal C conjugate vaccine failure in the United Kingdom.

BACKGROUND: The meningococcal serogroup C conjugate (MCC) vaccine was introduced into the United Kingdom with licensure based on immunogenicity data not efficacy data. METHODS: All subjects with laboratory-confirmed meningococcal serogroup C (MenC) disease from January 2000 to December 2003 in England and Wales were followed up. A vaccine failure was defined as a laboratory-confirmed case of MenC disease occurring > or =10 days after the subject's last scheduled dose of MCC vaccine. Total immunoglobulins, serum bactericidal antibody (SBA) titers, MCC anticapsular antibody levels, and avidity indices (AIs) were measured in acute and convalescent serum samples from subjects with vaccine failure and unvaccinated subjects with MenC disease. RESULTS: Of 465 subjects with confirmed MenC disease identified among those eligible for vaccination, information on vaccination history was obtained for 462 (99.4%); of these, 53 were subjects with vaccine failure. SBA titers in convalescent serum samples and AIs in acute serum samples were significantly higher in subjects with vaccine failure than in unvaccinated subjects, (6.1-fold higher for SBA titers [P=.03] and 3.2-fold higher for AIs [P=.001]). CONCLUSIONS: The antibody response in the subjects with vaccine failure was consistent with an anamnestic response, suggesting that MenC disease occurred despite the MCC vaccine priming for immune memory. Persistence of antibodies may be a more appropriate correlate of long-term protection for MCC vaccines than the ability to generate a booster response on exposure.

Adolescent↗
PubMed1992

Epidemic meningococcal disease in Nairobi, Kenya, 1989. The Kenya/Centers for Disease Control (CDC) Meningitis Study Group.

An epidemic of meningococcal disease occurred in Nairobi, Kenya, during 1989, outside the "meningitis belt" of sub-Saharan Africa. About 3800 cases occurred between April and November (250/100,000 population). The case-fatality rate was 9.4% among hospitalized patients. Areas that included Nairobi's largest slums had particularly high attack rates. The epidemic displayed an unusual age distribution, with high attack rates among those 20-29 years old. A vaccination campaign was conducted. By early January, the weekly case count had fallen to 25 from a high of 272 (in September). A case-control study estimated the vaccine efficacy to be 87% (95% confidence interval, 67%-95%). A model estimated that the vaccination campaign reduced the number of cases by at least 20%. Multilocus enzyme electrophoretic typing demonstrated that the strain responsible for this large epidemic is closely related to strains that caused other recent epidemics, documenting further spread of what may be a particularly virulent clonal complex of group A Neisseria meningitidis.

Adolescent↗
PubMed1995

The effect of variations in the expression of pili on the interaction of Neisseria meningitidis with human nasopharyngeal epithelium.

Bacterial adherence is essential to colonization of the nasopharynx by Neisseria meningitidis, and pili may facilitate adherence. Scanning electron microscopy and immunogold labeling were used to study the interaction of 2 piliated and 1 nonpiliated variant of N. meningitidis with nasopharyngeal mucosa in an adenoid organ culture system with an air-mucosal interface. Meningococcal infection caused epithelial damage, loss of ciliated epithelium, and ciliary disorganization, which progressed with time and were greater with the piliated strains. Pili increased adherence of meningococci to the mucosa, and there was tropism of piliated strains for nonciliated cells containing microvilli, damaged epithelium, and sites of cell separation. Bacterial adherence was associated with a change in the appearance of the microvilli.

Adenoids↗
PubMed1997

No increase in endotoxin release during antibiotic killing of meningococci.

Endotoxin is liberated following antibiotic killing of Gram-negative rods, and antibiotics may differ in this respect. Although the amount of filterable endotoxin has also been reported to increase following antibiotic killing of meningococci, it is unknown how this influences the host response. We investigated the influence of three antibiotics on levels of free endotoxin in culture medium and cytokine production in whole blood ex vivo during killing of four strains of meningococci. Bacterial killing was significantly more efficient with penicillin or ceftriaxone than with chloramphenicol, and free endotoxin levels were lower after exposure to antibiotics as compared with no treatment (ANOVA, P < 0.001). Endotoxin levels were lowest after exposure to chloramphenicol. In three of the four strains exposure to antibiotics resulted in considerably lower cytokine levels (ANOVA, P < 0.001), and TNF-alpha levels were significantly lower after exposure to penicillin or ceftriaxone than after chloramphenicol treatment. Only in the strain that induced the lowest levels of TNF-alpha were cytokine levels comparable for untreated and treated samples. We conclude that fear of excessive endotoxin release or cytokine production caused by effective antibiotics is not justified in the treatment of meningococcal infections.

Anti-Bacterial Agents↗
PubMed1993

Reliability of notification data for childhood bacterial meningitis.

This study reports the notification rates over ten years (1980-1989) for 232 children with documented bacterial meningitis in Nottingham District Health Authority. The average notification rate was approximately 50 per cent of known cases. It was higher for meningococcal infections (57/84, 68 per cent) than for any other type (45/148, 30 per cent), and lower in neonates (1/29, 3 per cent) than in any other age group (101/203, 50 per cent). The results show that the notification rates required to be adjusted during the decade of the study (1980-1989). The achievement of better notification rates may now be more feasible since implementation of the recommendations of the Committee of Inquiry into the Future Development of the Public Health Function for the control of communicable diseases. This paper provides a baseline upon which to measure the impact of such changes.

Adolescent↗
PubMed2002

Meningococcal disease: how to prevent and how to manage.

Meningococcal disease is a significant problem in the paediatric population. The diagnosis of meningococcal disease can be problematic and progression of the disease can rapidly lead to a life-threatening illness. Despite the success of antibiotic treatment, mortality rates remain high. The development of protein-polysaccharide conjugate vaccines has significantly improved the success of vaccination in reducing the incidence of meningococcal disease. However, a comprehensive vaccine conferring protection against disease-associated serogroups remains elusive. The aim of this review is to highlight recent significant improvements in the prevention and management of meningococcal disease.

Child↗
PubMed1998

The rationale for population-based surveillance for Haemophilus influenzae type b meningitis.

Although Haemophilus influenzae type b (Hib) conjugate vaccines have been spectacularly successful, nearly eradicating Hib disease in countries where used routinely, they are relatively expensive. In many countries the incidence of Haemophilus influenzae type b (Hib) disease is uncertain, and it is unclear whether the local burden of Hib disease warrants the costs of adding Hib vaccine to the routine immunization program. Population-based surveillance to assess the local burden of Hib disease can help decision makers with this process. Although pneumonia is more common than meningitis, surveillance for Hib meningitis and invasive disease is likely to be more feasible and efficient than surveillance for Hib pneumonia. Standardization of laboratory methods for the isolation and identification of H. influenzae from CSF specimens is essential to successful surveillance. Should a country decide to introduce Hib conjugate vaccine as a routine immunization, population-based surveillance data collected before and after the introduction of vaccine can be used to monitor its impact. Finally population-based surveillance for bacterial meningitis also can provide information on the incidence of pneumococcal and meningococcal infections and on serogroup or serotype distributions that will be important when evaluating the new vaccines for those pathogens that are being developed.

Child, Preschool↗
PubMed1998

Age-related immunogenicity of meningococcal polysaccharide vaccine in aboriginal children and adolescents living in a Northern Manitoba reserve community.

OBJECTIVE: To determine the total and functional serogroup C antibody response to a quadrivalent meningococcal polysaccharide vaccine in a group of aboriginal infants, children and adolescents. A secondary objective was to determine their prevalence of meningococcal carriage. DESIGN: Open prospective, before and after intervention study. SUBJECTS: Aboriginal children ages 0.5 to 19.9 years, living in a single Northern community and eligible for a public health immunization campaign conducted in all Manitoba native reserve communities to control a meningococcal serogroup C, electrophoretic type (ET) 15 outbreak. No outbreak cases had occurred in the community at the time of the study. METHODS: Total serogroup C capsular polysaccharide antibody (CPA) and functional bactericidal antibody (BA) responses were measured by enzyme-linked immunosorbent assay and bactericidal assay, respectively. RESULTS: Neisseria meningitidis was recovered from the oropharynx of 13 (5.2%) of 249 aboriginal children including 4 (1.6%) serogroup C isolates, all with the designation C:2a:P1.2,5 ET15. Paired sera from 152 children were available for assay. For CPA the geometric mean concentrations and proportions with > or =2 microg/ml before and after immunization were 0.69, 18% and 12.3, 96%, respectively. A significant increase in serum CPA was achieved by children of all ages, with the greatest response occurring after age 11 years. Among infants < lyear old 89% achieved concentrations of > or =2 microg/ml. For BA the pre- and post-vaccine geometric mean titers were 1.02 and 45.9. The response was significantly associated with age. BA titers > or =1:8 were present, before and after immunization, respectively, in 0 and 0% of infants <1 year old, 0 and 20% of 1- to 1.4-year-olds, 0 and 50% of 1.5- to 1.9-year-olds and 1 and 100% of > or =2-year-olds. CONCLUSION: The age-related total and functional group C meningococcal antibody response after quadrivalent polysaccharide vaccine among aboriginals is similar to that reported for Caucasian children. After age 2 all children made excellent CPA and BA responses. In the younger age groups the BA response was blunted but 82 to 95% achieved CPA titers of > or =2 microg/ml.

Adolescent↗
PubMed2002

Safety and immunogenicity of meningococcus serogroup C conjugate vaccine administered as a primary or booster vaccination to healthy four-year-old children.

BACKGROUND: Meningococcal C conjugate (Men C) vaccines have been routinely used in the UK since November, 1999. Little information exists regarding antibody persistence or immunologic memory after infant vaccination or response to a first dose at 4 years. METHODS: Ninety-five children immunized at 2, 3 and 4 months of age with 0 or 3 doses of Men C vaccine, boosted with Men C or meningococcal A/C polysaccharide vaccine at 12 months, received a single dose of Men C vaccine at 4 years; 103 age-matched controls were recruited. Pre- and postvaccination Men C IgG (enzyme-linked immunosorbent assay) antibody titers and serum bactericidal activity (SBA) were measured. Safety data were also collected. RESULTS: Baseline SBA titers of > or =1/4 were observed in 87% of children after at least 3 doses of Men C vaccine in infancy compared with 21% of controls. Reciprocals of postvaccination SBA geometric mean titers in those with four prior doses [3803 (95% confidence interval 3489, 4146)] were significantly higher than controls [33 (95% confidence interval 20, 55)] ( < 0.001). Memory was attenuated by the 12-month meningococcal A/C polysaccharide booster [734 (95% confidence interval 484, 1115)] ( < 0.001). All children had IgG responses to a first dose of Men C vaccine, 80% achieving SBA titers of > or =1/4 (77% > or =1/8). The vaccine was safe and well-tolerated. CONCLUSION: Infant immunization with Men C produced persistent antibody and immunologic memory at 4 years. All children made IgG antibodies after a first dose at this age, with 80% showing bactericidal activity. Clarification of the best measures of Men C vaccine-induced protection is needed, through correlation of immunogenicity data such as this with UK vaccine efficacy estimates.

Antibodies, Bacterial↗
PubMed2004

Protective activity of group C anticapsular antibodies elicited in two-year-olds by an investigational quadrivalent Neisseria meningitidis-diphtheria toxoid conjugate vaccine.

BACKGROUND: Quadrivalent capsular group A, C, Y and W-135 meningococcal conjugate (MC-4) vaccines are under development OBJECTIVE: Predict efficacy of an investigational MC-4 vaccine in 2-year-old children for prevention of group C disease. DESIGN: Measurement of group C antibody concentrations, avidity and bactericidal and passive protective activity in sera from 2-year-olds given 1 dose of MC-4 vaccine (N = 30) and 3-year-olds (N = 30) and adults (N = 26) given 1 dose of meningococcal polysaccharide (MPS-4) vaccine. RESULTS: One month after vaccination, the geometric mean anticapsular antibody concentration of children given MC-4 vaccine (3.1 microg/ml) was lower than that of control children (5.1 microg/ml; P < 0.04) or adults immunized with MPS-4 vaccine (22.9 microg/ml; P < 0.001). However, the percent of sera with protective bactericidal titers of >/=1/4 was higher in children given MC-4 vaccine (50%, versus 17% in children given MPS-4 vaccine; P < 0.02) and was not significantly different from that of immunized adults (65%). In children, the mean antibody avidity at 1 month was higher in the MC-4 group (22 nM versus 16 nM in the MPS-4 group; P = 0.002), and at 6 months increased in the MC-4 group (28 nM; P < 0.001), but not in the MPS-4 vaccine group (17 nM). Higher avidity antibody gave greater passive protection in the infant rat bacteremia model than did lower avidity antibody (P < 0.03). CONCLUSIONS: Although MPS-4 vaccine elicited higher group C serum antibody concentrations in 3-year-olds than did MC-4 vaccine in 2-year-olds, the higher antibody avidity after MC-4 vaccine resulted in higher bactericidal and passive protective activity.

Analysis of Variance↗
PubMed2005

Comparative trial of the safety and immunogenicity of quadrivalent (A, C, Y, W-135) meningococcal polysaccharide-diphtheria conjugate vaccine versus quadrivalent polysaccharide vaccine in two- to ten-year-old children.

BACKGROUND: A quadrivalent meningococcal diphtheria conjugate vaccine (MCV-4) has been developed to provide T-cell dependent immune responses against 4 major disease-causing serogroups (A, C, Y, W-135). METHODS: In a comparative, randomized, modified double blind, controlled study in healthy 2- to 10-year-old U.S. children, safety and immunogenicity profiles of MCV-4 (n = 696) were compared with those of a licensed quadrivalent polysaccharide vaccine, Menomune A/C/Y/W-135 (PSV-4, n = 702). Vaccine-related adverse reactions were assessed for 28-day and 6-month follow-up periods. Serum bactericidal activity (SBA) was assayed in prevaccination, day 28 and 6-month postvaccination sera samples. RESULTS: Both vaccines were well-tolerated, with no vaccine-related serious adverse events and similar rates of mostly mild local and systemic reactions. Functional antibody (SBA) seroconversion percentages were significantly higher for all 4 serogroups in the MCV-4 group. The SBA geometric mean titers against serogroups A, C, Y and W-135 with MCV-4 were 1700, 354, 637 and 750, respectively, compared with PSV-4 (893, 231, 408 and 426) 28 days postvaccination (P < 0.001 for all comparisons). This significant difference persisted through 6 months. CONCLUSIONS: In 2- to 10-year-old children MCV-4 had a safety profile similar to that of PSV-4 and elicited significantly higher and more persistent serum bactericidal antibody responses against meningococcal serogroups A, C, Y and W-135 than did the licensed polysaccharide vaccine.

Antibodies, Bacterial↗