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PubMed2005

Increased genetic diversity of Neisseria meningitidis isolates after the introduction of meningococcal serogroup C polysaccharide conjugate vaccines.

During the 1990s, the incidence of meningococcal disease was high in the United Kingdom. This was due primarily to an increase in serogroup C disease, particularly that within the ET-37/ST-11 genetic lineage. Serogroup C meningococcal polysaccharide conjugate vaccines were introduced in the United Kingdom in 1999, but the sequence types of meningococci causing disease since that time have not yet been reported. We have used serogrouping and multilocus sequence typing to characterize meningococci from patients with invasive disease over a 4-year period and show that there is a significant increase in genetic diversity but no genetic evidence of capsule switching.

Genetic Variation↗
PubMed2006

Tacrolimus ointment does not affect the immediate response to vaccination, the generation of immune memory, or humoral and cell-mediated immunity in children.

BACKGROUND: Concern exists that the prolonged application of immunomodulators to treat atopic dermatitis may cause systemic immunosuppression. AIMS: In a 7-month, multicentre, randomised, controlled trial, we investigated the equivalence of response to vaccination against meningococcal serogroup C disease with a protein-conjugate vaccine in children (2-11 years) with moderate to severe atopic dermatitis, by applying either 0.03% tacrolimus ointment (TAC-O; n = 121[corrected]) or a hydrocortisone ointment regimen (HC-O; n = 111). METHODS: TAC-O was applied twice daily (bid) for 3 weeks, and thereafter daily until clearance. 1% hydrocortisone acetate (HA) for head/neck and 0.1% hydrocortisone butyrate ointment for trunk/limbs was applied bid for 2 weeks; thereafter HA was applied bid to all affected areas. At week 1, patients were vaccinated with protein-conjugate vaccine against meningococcal serogroup C, and challenged at month 6 with low dose meningococcal polysaccharide vaccine. The control group (44 non-atopic dermatitis children) received the primary vaccination and challenge dose. Assessments were made at baseline, weeks 1 and 5, and months 6 and 7. The primary end point was the percentage of patients with a serum bactericidal antibody (SBA) titre > or = 8 at the week 5 visit. RESULTS: The response rate (patients with SBA titre > or = 8) was 97.5% (confidence interval (CI) approximately 97.3 to 100), 99.1% (94.8 to 100) and 97.7% (93.3 to 100) in the TAC-O, HC-O and control groups, respectively. CONCLUSIONS: The immune response to vaccination against meningococcal serogroup C in children with atopic dermatitis applying either 0.03% TAC-O or HC is equivalent. Ointment application does not affect the immediate response to vaccination, generation of immune memory or humoral and cell-mediated immunity.

Administration, Topical↗
PubMed2001

Safety of a new conjugate meningococcal C vaccine in infants.

BACKGROUND: Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999. There has been extensive professional and public interest in their efficacy and safety. AIM: To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine. METHODS: A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine. RESULTS: There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

Female↗
PubMed2002

Modelling cost effectiveness of meningococcal serogroup C conjugate vaccination campaign in England and Wales.

OBJECTIVES: To assess the cost effectiveness of a meningococcal serogroup C conjugate vaccination campaign in 0-17 year olds. DESIGN: Cost effectiveness analysis from the perspective of the healthcare provider. SETTING: England and Wales. MAIN OUTCOME MEASURE: Cost per life year saved. RESULTS: In 1998-9, immediately before the introduction of meningococcal C vaccination, the burden of serogroup C disease was considerable, with an estimated 1137 cases in people aged 0-17 years and at least 72 deaths. The vaccination campaign is estimated to have cost between 126m pound sterling ($180m, 207m) and 241 pound sterling 3m, 395m), depending on the price of the vaccine. Under base case assumptions the cost per life year saved from the vaccination campaign is estimated to be 6259 pound sterling. School based vaccination was more cost effective than general practice based vaccination because of lower delivery costs. Immunisation of infants aged under 1 year was the least cost effective component of the campaign because, although this maximises the life years gained, the three dose schedule required is more expensive than other methods of delivery. Estimates of the cost per life year saved were sensitive to assumptions on the future incidence of disease and the case fatality ratio. CONCLUSIONS: Meningococcal C vaccination is likely to be more cost effective in all age groups when the incidence of disease is high. It is also more cost effective when given to children aged 1-4 (by general practitioners) and to children and young people aged 5-17 years at school than when administered to infants under 12 months of age or young people aged 16-17 years who are not at school.

Adolescent↗
PubMed2006

Risk and protective factors for meningococcal disease in adolescents: matched cohort study.

OBJECTIVE: To examine biological and social risk factors for meningococcal disease in adolescents. DESIGN: Prospective, population based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls were sought from the general practitioner. SETTING: Six contiguous regions of England, which represent some 65% of the country's population. PARTICIPANTS: 15-19 year olds with meningococcal disease recruited at hospital admission in six regions (representing 65% of the population of England) from January 1999 to June 2000, and their matched controls. METHODS: Blood samples and pernasal and throat swabs were taken from case patients at admission to hospital and from cases and matched controls at interview. Data on potential risk factors were gathered by confidential interview. Data were analysed by using univariate and multivariate conditional logistic regression. RESULTS: 144 case control pairs were recruited (74 male (51%); median age 17.6). 114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4 to 5.9), intimate kissing with multiple partners (3.7, 1.7 to 8.1), being a university student (3.4, 1.2 to 10) and preterm birth (3.7, 1.0 to 13.5). Religious observance (0.09, 0.02 to 0.6) and meningococcal vaccination (0.12, 0.04 to 0.4) were associated with protection. CONCLUSIONS: Activities and events increasing risk for meningococcal disease in adolescence are different from in childhood. Students are at higher risk. Altering personal behaviours could moderate the risk. However, the development of further effective meningococcal vaccines remains a key public health priority.

Adolescent↗
PubMed2004

Opportunities for control of meningococcal disease in the United States.

The United States currently has relatively low rates of meningococcal disease caused by Neisseria meningitidis. Serogroups Y, C, and B are most common. Although most cases are sporadic, a minority are associated with outbreaks. Pediatric populations have disproportionately higher rates of disease, but nearly two thirds of all cases occur in persons aged 15 years and older. The major challenge to control of domestic meningococcal disease is the absence of a vaccine to prevent sporadic cases spanning many age groups. The quadrivalent A/C/Y/W-135 meningococcal polysaccharide vaccine is licensed in the United States, but because of its limited efficacy in children under two years of age, it is recommended for high-risk groups and outbreak response rather than routine childhood immunization. New conjugate meningococcal vaccines have successfully reduced endemic disease in the United Kingdom, and similar vaccines promise to have a dramatic impact on the burden of meningococcal disease in the United States.

Anti-Bacterial Agents↗
PubMed2006

[Current situation of the epidemiology of meningococcal disease].

Neisseria meningitidis, the etiological agent of all forms of meningococcal disease, is still a cause for concern among society in general and especially among health workers. Several of its antigens have been used in strain characterization, and some have served as the basis for the development of vaccines. In this sense, the best known are the capsular polysaccharide, which defines the serogroups, the outer membrane protein of class 2/3, used for serotype classification, and the class 1 porins, defining the serosubtype. During the last 30 years, most cases of meningococcal disease in Spain have been due to serogroup B strains, with the exception of 1996 and 1997, when serogroup C cases became the most frequent. The capsular polysaccharide has been successfully used in the development of conjugate vaccines highly effective against A, Y and W135 serogroups and particularly against serogroup C isolates. The development of a vaccine against serogroup B strains for routine immunization is still uncertain. However, the use of specific vaccines based on antigenic formulations of class 1 protein, to be applied in epidemic situations, is closer to becoming a reality. Because of the current absence of a universal vaccine against N. meningitidis, specific surveillance programs are required to evaluate the importance of recombination processes affecting capsular expression. This type of event could produce new strain variants able to avoid the immunological response generated after vaccination.

Forecasting↗
PubMed2005

Discrepancy between tissue factor activity and tissue factor expression in endotoxin-induced monocytes is associated with apoptosis and necrosis.

Tissue factor (TF), the main initiator of blood coagulation, contributes to the manifestation of disseminated intravascular coagulation following septic shock in meningococcal infection. Since a direct relationship between disease severity and lipopolysaccharide (LPS) concentration in the circulation has been shown, we hypothesized that the procoagulant and cytotoxic effects of endotoxin also in vitro were related to its concentration. In vitro studies, however, have frequently used much higher LPS concentrations than those observed in clinical samples. Using elutriation-purified human monocytes, we observed that LPS up to 1000 ng/ml exerted a concentration-dependent increase in TF activity (tenase activity, fibrin formation in plasma). Although there was a dose-dependent increase in TF activity, there was not a concomitant increase in TF expression at LPS concentrations above 1 ng/ml (flow cytometry, Western blotting, TF mRNA). Flow cytometry revealed that this discrepancy between TF activity and TF expression at endotoxin concentrations above 1 ng/ml, coincided with an LPS dose-dependent increase in cell surface phosphatidylserine (PS), considered to promote coagulation. The increased PS expression was associated with an increased number of 7-AAD-positive cells indicating cell death. We conclude that enhancement of monocyte procoagulant activity in vitro by high concentrations of LPS may result from increased PS exposure due to apoptosis and necrosis. Therefore, the LPS concentrations used to examine monocyte procoagulant activity in vitro, should be carefully chosen.

Annexin A5↗
PubMedDate not supplied

Meningococcal conjugate vaccine in adolescents and children.

Disease caused by Neisseria meningitidis is associated with high mortality rates and significant sequelae. Quadrivalent (A, C, Y, W-135) polysaccharide meningococcal vaccine has been available for more than 20 years, and although used widely for adolescents entering college, it has a number of limitations, including short duration of immunity and lack of a herd effect. A quadrivalent meningococcal conjugate vaccine has recently been licensed and endorsed for use in adolescents 11 to 12 years of age, at age 15, or at college entry. Among the key features of the new meningococcal conjugate vaccine are stimulation of both B-cell-dependent and T-cell-dependent immune responses, induction of immunologic memory and booster effects, long-term protection, reduction of nasopharyngeal carriage of N. meningitidis, and herd immunity. Large randomized, double-blind studies in adolescents and 2- to 10-year olds have demonstrated the immunogenicity as well as the safety and tolerability of the new meningococcal conjugate vaccine formulation.

Adolescent↗
PubMed2006

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study.

BACKGROUND: A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood. METHODS: We examined the relation between CSF WBC, bacteraemia and sepsis in a prospective cohort study that included 352 episodes of pneumococcal meningitis, confirmed by CSF culture, occurring in patients aged >16 years. RESULTS: CSF WBC was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm3 (interquartile range 531-6983 per mm3) and 104 patients (33%) had a CSF WBC <1000/mm3. Patients with a CSF WBC <1000/mm3 were more likely to have an unfavourable outcome (defined as a Glasgow Outcome Scale score of 1-4) than those with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was significantly associated with blood WBC (Spearman's test 0.29), CSF protein level (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C-reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm3 more often had a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more often developed systemic complications (cardiorespiratory failure, sepsis) than those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22, 95%CI 1.02-1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17-5.14), and a low thrombocyte count on admission (Odds ratio per 100,000/mm3 increments 0.67, 95% CI 0.47-0.97) were associated with a CSF WBC <1000/mm3. CONCLUSION: A low CSF WBC in adults with pneumococcal meningitis is related to the presence of signs of sepsis and systemic complications. Invasive pneumococcal infections should possibly be regarded as a continuum from meningitis to sepsis.

Adult↗
PubMed2002

Epidemiology of meningococcal disease.

In the UK, serogroup A strains disappeared 50 years ago, but in the 1990s, numbers of cases rose again to a 50-year high. Following the very successful introduction of conjugated meningitis C vaccines, effective meningitis B vaccines are now the highest priority.

Adolescent↗