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Is group-specific meningococcal vaccination resulting in epidemics caused by groups of virulent meningococci?

In 1976 routine vaccination against Neisseria meningitidis serogroups A and C was started in the Finnish Armed Forces. A case of fulminant, complicated pneumonia caused by group-Y meningococcus in a vaccinated recruit, prompted a study of the distribution of the meningococcal groups isolated from the recruits in the same unit. 14 (46%) of the 31 isolates from 84 recruits were group Y. Group-Y meningococcus was rarely isolated from unvaccinated controls. These results suggest that widespread vaccination against serogroups A and C may have led to an increase in the frequency of meningococcus group Y.

Bacterial Vaccines↗

Rapid detection of meningococci from petechiae in acute meningococcal infection.

In order to evaluate the diagnostic usefulness of Gram-staining films from petechial lesions in suspected meningococcal infection, data from 52 patients with confirmed infection were reviewed. Gram-negative diplococci were found in specimens from skin films in 80% (24/30) patients with petechiae. This is significantly better than results reported for Gram-staining of needle aspirates from petechiae (46%; 12/26). Positive skin films were obtained from 89% (17/19) blood culture negative cases and 85% (17/20) CSF negative cases. In 14 cases meningococcal infection was identified only by skin films. Skin film results were not significantly affected by previous antibiotic. Gram-staining of films from petechial lesions in suspected meningococcal infection is a very rapid and effective investigation. Blood culture, CSF examination and culture, and skin films each identified meningococcal infection not identified by the other two investigations.

Acute Disease↗

The infant rat model adapted to evaluate human sera for protective immunity to group B meningococci.

The infant rat infection model previously developed to evaluate protective ability of passively administered murine antibodies to group B meningococcal (MenB) surface antigens was adapted for human sera. Several challenge doses were tested, aiming at sensitive detection of protection with little interassay variability. Doses of 10(5) and 10(6) colony forming units of strain IH5341 (MenB:15:P1.7,16) injected intraperitoneally gave consistently high levels of bacteremia and meningitis developed in 6 h in 50-100% of the pups. A monoclonal antibody mAb735 to the MenB capsule, injected 1-2 h before bacterial challenge, gave full protection at a dose of 2 microg/pup. Sera from adult volunteers immunized with a MenB outer membrane vesicle vaccine reproducibly reduced bacterial counts in the blood and cerebrospinal fluid, whereas a normal human serum, lacking bactericidal and opsonophagocidal activity, was unprotective.

Adult↗

Hypermutation in pathogenic bacteria: frequent phase variation in meningococci is a phenotypic trait of a specialized mutator biotype.

Expression of serogroup B meningococcal capsular polysaccharide undergoes frequent phase variation involving reversible frameshift mutations within a homopolymeric repeat in the siaD gene. A high rate of phase variation is the consequence of a biochemical defect in methyl-directed mismatch repair. The mutator phenotype is associated to the absence of DNA adenine methyltransferase (Dam) activity in all pathogenic isolates and in 50% of commensal strains. Analysis of the meningococcal dam gene region revealed that in all Dam- strains a gene encoding a putative restriction endonuclease (drg) that cleaves only the methylated DNA sequence 5'-GmeATC-3' replaced the dam gene. Insertional inactivation of the dam and/or drg genes indicated that high rates of phase variation and hypermutator phenotype are caused by absence of a functional dam gene.

Amino Acid Sequence↗

Interaction mechanisms of encapsulated meningococci with eucaryotic cells: what does this tell us about the crossing of the blood-brain barrier by Neisseria meningitidis?

An important feature of Neisseria meningitidis is its ability to invade the meninges. This requires that bacteria cross the blood-brain barrier (BBB), which is one of the tightest barriers of the body. N. meningitidis has, therefore, evolved very sophisticated means by which it circumvents the physical properties of this cellular barrier. Recent advances have allowed the identification of several steps that might occur in the interaction of N. meningitidis with the BBB and the transit of the bacteria to the meninges.

Antigenic Variation↗

Acquisition and carriage of meningococci in marine commando recruits.

Meningococcal acquisition is a prerequisite for invasive disease. Three hundred and eleven male marine commando recruits were studied throughout 29 weeks of basic training to identify factors influencing meningococcal carriage and acquisition including troop number, season, smoking, respiratory infection, antibiotic usage and nasopharyngeal bacterial interference flora. A high carriage rate on entry to training (118/311, 37.9%) and subsequent sustained high rates of meningococcal acquisition were found. Of the potential factors examined, only active and passive smoking were found to be associated significantly with meningococcal carriage on entry. The association between active smoking and meningococcal carriage was dose-dependent, with odds ratios (OR) of 2.2 (95% CIs 1.0-4.8) and 7.2 (95% CIs 2.3-22.9) for light and heavy smokers respectively. Passive smoking predisposed independently to carriage (OR 1.8, 95% CIs 1.1-3.0). Active and passive smoking combined to give an attributable risk for meningococcal carriage of 33%. In contrast, despite a high and sustained rate of meningococcal acquisition in the study population, none of the risk factors investigated, including active smoking, was associated significantly with meningococcal acquisition. No cases of meningococcal disease occurred during the 16-month study period. Therefore smoking may increase the duration of meningococcal carriage rather than the rate of acquisition, consistent with the increased risk of meningococcal disease from passive as opposed to active smoking. Public health measures that reduce the prevalence of smoking should reduce the risk of meningococcal disease.

Adult↗