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PubMed2003

Meningococcal serogroup B infections: a search for a broadly protective vaccine.

Meningococcal disease is mainly caused by serogroup B in many West European countries. Recently, a highly efficacious vaccine against infections caused by serogroup C has been introduced in the UK and The Netherlands. However, an effective vaccine against serogroup B has not yet become available. Outer membrane vesicle vaccines against serogroup B were previously tested in large Phase III trials but showed a low efficacy in young children. In addition, the high variability of the vaccines' main component, porin A, potentially diminishes its efficacy. Therefore, several approaches in either optimizing these outer membrane vesicle vaccines or searching for novel, highly conserved antigens are currently under investigation. The sequencing of the meningococcal genome has provided new opportunities to detect additional immunogenic epitopes. In this review, the developments in the search for a broadly protective meningococcal serogroup B vaccine will be discussed.

Animals↗
PubMed1981

[Relation between the results of gel filtration and electrophoresis of serotype A and G meningococcal polysaccharides].

Meningococcal polysaccharides, serogroups A and C, produced for the vaccinal prophylaxis of meningococcal infection, were found to have pronounced electrophoretic homogeneity in their movement towards the anode in the process of immunoelectrophoresis in agarose gel with pH 8.6. In gel filtration through Sepharose 4B the serologically active substance of meningococcal polysaccharides, groups A and C, was eluted in a wide range of Kd values from 0 to 0.9. The immunoelectrophoresis of the samples isolated in gel filtration and having definite Kd values indicated that the regular increase of electrophoretic mobility towards anode occurred as the size or weight of molecules decreased.

Chemical Phenomena↗
PubMed1969

The chick embryo neutralization test in the assay of meningococcal antibody. 1. Infection of the embryo with Neisseria meningitidis.

Present methods of controlling meningococcal cerebrospinal meningitis have failed to contain the disease. This has led to the search for effective vaccines and to the development of methods for assaying the potency of these vaccines, as well as for measuring the immune response of the individual. The feasibility of using the sero-protection test in embryonated eggs for the assay of meningococcal antibody has been investigated. The paper describes detailed investigations of the infectious process established by injecting Neisseria meningitidis by various challenge routes. Embryos, even 10-12 days old, showed high susceptibility to meningococci injected via the yolksac or chorioallantoic vein, and lesser susceptibility when injected via the intra-allantoic and chorioallantoic routes. The deaths of intravenously inoculated embryos coincided with the multiplication of the organisms and ensuing septicaemia. A study of the infection in embryos which had died, or were killed, 18-24 hours after inoculation showed a specific localization of the organisms in the brain.

Animals↗
PubMed2006

Immunization update: pertussis, meningoccocus, and human papillomavirus.

New vaccines are being recommended for adolescents at a brisk pace. Immunization is an effective preventive measure, and by bringing adolescents in for a medical intervention, the new vaccines promise not only to protect adolescents from the specific diseases they address, but also to enhance other health care services, including screening for other health risk behaviors. This article discusses the newest vaccination recommendations for adolescents pertaining to the meningococcal and tetanus, diphtheria, and acellular pertussis vaccines and reviews the human papillomavirus vaccines developed for use in the United States. With the advent of these new vaccines, the potential exists to improve adolescent health significantly through prevention, adding new incentive to increase adolescent immunization rates for all indicated vaccines.

Adolescent↗
PubMed2000

Effect of individual conjugate dose on immunogenicity of type 6B pneumococcal polysaccharide-N. meningitidis outer membrane protein complex conjugate vaccines in infant rhesus monkeys.

A pneumococcal conjugate vaccine (PCV) has been developed consisting of capsular polysaccharide (Ps) coupled to the outer membrane protein complex of Neiserria meningitidis serogroup B. Experiments were conducted in infant rhesus monkeys to assess the potential to administer multiple Pn types in a single vaccine. A single type conjugate, 6B, was dosed from 0.025 to 25 microg Ps. Peak anti-6B Ps Ab titers were seen at lower doses of 0.025 and 0.25 microg Ps, while reduced titers of anti-6B Ps Ab were observed at the highest doses of conjugate administered, 2.5 and 25 microg Ps. By mixing free Ps, carrier, or another monovalent PCV with this 6B PCV, it was determined that reduced anti-6B Ps titers at high PCV doses were associated only with the quantity of type-specific Ps in the conjugate. Thus, increasing the amount of carrier protein or adding an additional monovalent conjugate did not significantly affect the response to type 6B Ps. These results suggest that, given an appropriately determined dose per individual pneumococcal Ps type, a multivalent PCV that includes many different types should have satisfactory clinical immunogenicity.

Animals↗
PubMed1991

[The effect of the nature of the strain on the character of the production of iron-dependent proteins by meningococci].

The comparative study of three Neisseria meningitidis strains (15, 125, 2394) was carried out by the method of electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate and by the method of immunoblotting. The intensive expression of 8 iron-regulated proteins (IRP) was shown to occur in iron-deficient culture medium. The major IRP with a molecular weight of 35 kD was expressed by all above-mentioned N. meningitidis strains under the conditions of iron deficiency and cross-reacted with 10 mouse and rabbit antisera to N. meningitidis of different groups, i.e. it was common to all Neisseria species. The antigenic activity of various IRP essentially differed with respect to antisera of animals and sera of patients with meningococcal infection.

Animals↗
PubMed1994

Low levels of vitronectin and clusterin in acute meningococcal disease are closely associated with formation of the terminal-complement complex and the vitronectin-thrombin-antithrombin complex.

Patients with terminal complement deficiencies and thus impaired lytic efficiency have a highly increased likelihood of contracting invasive meningococcal infections but generally experience a mild disease course. Deficiencies of lysis inhibitors might therefore be associated with severe disease. We have quantified the complement lysis inhibitors vitronectin and clusterin, as well as complexes containing the proteins, in plasma from patients with acute meningococcal disease. At hospital admission, the median vitronectin concentrations were 0.10 (range, 0.04 to 0.17) g/liter in 10 septic patients and 0.19 (0.09 to 0.47) g/liter in 14 nonseptic patients (P = 0.001). The corresponding clusterin concentrations were 0.09 (0.01 to 0.13) and 0.14 (0.06 to 0.29) g/liter (P = 0.005). The vitronectin-thrombin-antithrombin complex concentration was 1.8 (0.22 to 35.6) arbitrary units (AU)/ml in septic patients, but the complex was not detectable in most nonseptic patients (< 0.10 to 0.16 AU/ml) (P < 0.0001). The corresponding levels of the terminal complement complex (contains vitronectin and clusterin) were 4.4 (3.6 to 20.1) and 2.6 (1.6 to 4.7) AU/ml (P = 0.0005). We found no evidence of constitutively low levels of vitronectin or clusterin in patients contracting meningococcal disease. The low levels of the proteins may partly be explained by hemodilution, extravasation, and increased consumption due to incorporation into complexes which are quickly removed from circulation.

Adolescent↗
PubMed2002

Current concepts in the role of the host response in Neisseria meningitidis septic shock.

Lipopolysaccharides in the outer membrane of Neisseria meningitidis are key molecules that induce inflammation and cause meningitis and shock. Mutant strains, with altered lipid A, the toxic moiety of lipopolysaccharide, or completely lacking lipopolysaccharide, induce significantly less inflammation than wild-type strains. Polymorphism of the Fc gamma receptors and interleukin-10 gene but not of the Toll-like receptor 4 may influence the development of meningococcal infection. Mannan-binding lectin is involved in complement activation, the regulation of adhesion molecules and cytokine production induced by meningococci. The activation of protein C by the thrombomodulin protein C receptor complex on the endothelial cell surface appears to be reduced in meningococcal sepsis but is still sufficient to convert protein C to activated protein C in patients treated with concentrated protein C.

Carrier Proteins↗
PubMed1980

Intrafamilial meningococcal meningitis.

Two couples of sibs presented with meningococcal meningitis. In both families, immediate preventive measures were not taken due to a negative cerebrospinal fluid (CSF) smear in the first case from Family A, and a negative CSF smear and culture in the first case from Family B. All the children were treated successfully. Our recommendations are: a) contacts of patients with pyogenic meningitis should have close clinical surveillance, and b) contacts of meningococcal infection should have nasopharyngeal cultures and should be given a prophylactic antibiotic such as rifampicin or minocycline.

Adolescent↗
PubMed1976

Minocycline for prophylaxis of infection with Neisseria meningitidis: high rate of side effects in recipients.

A high rate of side effects (mostly vestibular) was found among 83 people receiving prophylaxis with minocycline because of contact with a patient who had died of meningitis due to Neisseria meningitidis. Three groups of contacts received different lots of minocycline and different dosage regimens. Seventy-eight percent of these people had symptoms temporally related to ingestion of minocycline. These symptoms, which included dizziness, nausea, vomiting, vertigo, anorexia, and headache, generally commenced soon after initiation of chemoprophylaxis; the total dosage of minocycline was low. The high rate of vestibular side effects of minocycline militates against widespread use of minocycline for prophylaxis of meningococcal infection.

Adult↗
PubMed2002

[Universal vaccination against group C meningococci and pneumococci; advice from the Health Council of the Netherlands].

A committee of the Health Council of the Netherlands recently advised the Minister of Health on nationwide vaccination against group-C meningococci and pneumococci. They recommended the introduction of both vaccines into the national vaccination programme. The meningococcal C vaccine should be introduced as soon as possible, and the pneumococcal vaccine should be introduced as soon as a combined vaccine against diphtheria, tetanus, pertussis and polio and H. influenzae type B is available. In the meantime, due to various clusters of meningococcal disease caused by Neisseria meningitidis C in the Netherlands, parents have started to have their children vaccinated by buying vaccines and asking their general practitioners to perform the vaccination. This unfavourable situation must be controlled by the government through clear publicity to parents and healthcare workers.

Health Policy↗
PubMedDate not supplied

[Characteristics of the course of the last epidemic of epidemic cerebrospinal meningitis (ECSM) in the city of Bucharest].

Active survey of the epidemiologic potential of cerebrospinal meningitis, in Bucharest, starting in 1967, made it possible to carry out a complex study of the last epidemic wave in 1968-1972. Details are given concerning the results of the complex epidemiologic, clinical and laboratory investigations, which revealed the particularities of this epidemic episode, including the frequency and gravity of the cases, territorial distribution, prevalent affection of certain age groups and children's communities, the prevalence of certain clinical forms, antigenic structure of the pathogenic agent and its sensitivity to antibiotics, comparative efficiency of the different methods of laboratory diagnosis, real and apparent contagiousness, etc. The authors discuss the efficiency of present methods applied in the prevention and control of meningococcal infections in general and of epidemic cerebrospinal meningitis in particular.

Adolescent↗
PubMed1996

Sialic acids of both the capsule and the sialylated lipooligosaccharide of Neisseria meningitis serogroup B are prerequisites for virulence of meningococci in the infant rat.

We investigated the contribution of the polysialic acid capsule and of terminal lipooligosaccharide (LOS) sialylation to the pathogenicity of Neisseria meningitidis in vivo using a set of defined isogenic mutants of the N. meningitidis strain B 1940 deficient in either capsule synthesis or LOS sialylation. Furthermore a spontaneous capsule-deficient variant was investigated, which was capable of switching on the capsule synthesis at a frequency of 3 x 10(-3) in vitro. Infection of infant rats with the wild-type strain revealed a high potential to cause bacteremia. This potential was attenuated in the capsule-phase variable mutant (LOS sialylation+). However, using a mutant irreversibly deficient in capsule synthesis, but expressing a sialylated LOS, bacteremia could only be achieved using 10(6) times higher numbers of bacteria when compared to the wild-type. The unencapsulated bacteria were located extracellularly upon examination of blood smears, suggesting that defense mechanisms, i.e. phagocytosis, directed against unencapsulated meningococci were exhausted using very high infecting doses. Interestingly, when infant rats were infected with encapsulated meningococci which were unable to sialylate the LOS, bacteremia could never be achieved, even with an infective dose as high as 10(8) colony forming units (CFU). Despite the presence of capsular polysaccharide this mutant was phagocytosed by peritoneal phagocytes, as was the unencapsulated, LOS-sialylated mutant, suggesting that the inability to cause bacteremia was due to a higher susceptibility to the action of the complement system, which is virtually unsaturable. We conclude that in the infant rat model of meningococcal infection both forms of sialic acid on the bacterial cell surface are indispensable for systemic survival.

Animals↗
PubMed1979

Cellular immunity in patients with meningococcal disease and in vaccinated subjects.

Cell-mediated immunity was studied in patients with group A meningococcal meningitis and in normal subjects given group A meningococcal vaccine. Lymphocytes responsiveness to phytohaemagglutinin and to meningococcal antigens was markedly depressed in patients with acute meningococcal infection. This defect was present when lymphocytes were cultured in autologous or foetal calf serum. Patients also showed a transient increase in the degree of inhibition produced by whole group A meningococci in leucocyte migration assays. Meningococci of other groups produced a similar degree of inhibition. Vaccination with group A meningococcal polysaccharide vaccine had no effect on lymphocytes responsiveness to meningococcal antigens or on the inhibitory effect of group A meningococci on leucocyte migration.

Adolescent↗
PubMed1993

Epidemiology of bacterial meningitis.

This 10 year retrospective study of all causes of bacterial meningitis for children resident in Nottingham District Health Authority area reports an annual incidence rate per 100,000 children aged 0-16 years of 16.0 (95% confidence interval 14.0 to 18.1). There was a steady increase in incidence from 9.6/100,000 in 1980 to 24.3/100,000 in 1989. This was mainly due to an increase in the incidence of meningococcal infections in the age group 1 month to 5 years. Incidence rates varied with age being: 37.2/100,000 (25.9 to 53.5) for 0-28 days of age, 115.5/100,000 (93.9 to 141.9) for 1-11 months of age, 28.5/100,000 (23.1 to 35.3) for 12-59 months of age, and 2.8/100,000 (1.9 to 4.1) for 5-16 years of age. Overall annual mortality incidence per 100,000 was 1.8 (1.2 to 2.8). For the different age groups this was: 10.1 (4.8 to 21.1) for 0-28 days, 11.5 (6.0 to 22.2) for 1-11 months, 1.0 (0.3 to 3.1) for 12-59 months, and 0.4 (0.1 to 1.2) for 5-16 years of age. There were interactions between the type of meningitis and the year of the infection on the mortality rate. Mortality decreased in those with infections caused by bacteria other than Neisseria meningitidis and Haemophilus influenzae.

Adolescent↗
PubMedDate not supplied

Characteristics of Neisseria meningitidis strains isolated in Romania between 1986 and 1989.

499 N. meningitidis strains were studied, 454 being isolated from CSF and blood and 45 from nasopharynx. Meningococcal serogroup A was prevalent in 1986-1988, having a decreasing tendency from 84.90% in 1987 to 45.0% in 1989. Serogroup C increased from 0.86% in 1986 to 15% in 1989. All strains, examined by diffusiometric method, were sensitive to ampicillin, cephalotin, chloramphenicol and rifampin. For tetracycline, resistance ranged from 2.28 to 6.0% in 1987-1989. The frequency of 52.0-72.14% resistant to sulphamides strains seems to be due to serogroup A prevalence. Six N. meningitidis strains, isolated in 1989, proved to be moderately resistant to penicillin with MIC greater than or equal to 0.1 mcg/ml. The results indicate the necessity of a continuous surveillance of meningococcal infection, both from the point of view of serogroup circulation and also of antibiotics sensitivity.

Anti-Bacterial Agents↗