Characteristics of Neisseria meningitidis isolates causing fatal disease

National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Orebro University Hospital, Orebro, Sweden.
Infectious Diseases (Impact Factor: 1.5). 02/2008; 40(9):734-44. DOI: 10.1080/00365540802029565
Source: PubMed


The objectives of the present study were to describe a selection of characteristics of all available fatal meningococcal isolates (n = 62) and to compare these with all the other invasive isolates (non-fatal, n = 474) collected in Sweden from 1995 to 2004 (fatality rate of 12%). The coverage of the fatal isolates by presently discussed outer membrane vesicle (OMV) vaccines was also estimated. The isolates were characterized by serogroup, serotype, genosubtype, multilocus sequence type and antibiogram. Basic epidemiological data were gathered. The results of the fatal isolates showed 55% serogroup B, 27% C, 15% Yand 3% W-135, with a fatality rate of 11% for B, 12% for C, 17% for Y and 8% for W-135. Characteristics associated with higher mortality were age, gender, serogroup Y, serotype 14 and 15 and genosubtypes P1.7,16-29,35 and P1.5-1,10-4,36-2. In contrast, non-14/non-15 serotypes, the genosubtypes P1.5-1,10-8,36-2; P1.7-2,4,37 and P1.7,16,35, as well as reduced sensitivity for penicillin G were associated with decreased mortality. The presently discussed OMV vaccines could, based solely on the complete genosubtype, theoretically cover up to 44% of the fatal serogroup B cases and up to 100% if every variable region by itself is capable to induce protective immunity.

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    • "In the United Kingdom, case fatality rates have been falling steadily since 1985, a trend which has been attributed to more efficient ascertainment of milder surviving cases [4], improvements in clinical management [6], [7], and the introduction of the meningococcal C conjugate vaccine [8]. The overall European picture has been similar to that in the United Kingdom, with overall case-fatality rates falling and the incidence of serogroup C disease also falling [9], [10], [11]. "
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    ABSTRACT: Meningococcal disease (MCD) is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM), septicaemia (MS), or as a combination of the two syndromes (MM/MS). We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary children's centre, Alder Hey Children's Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157). Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1-4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC) vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM) and serogroup C disease (compared to serogroup B) were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08) and 2.18 (95% CI 1.26 to 3.80) respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41) than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD.
    Full-text · Article · Oct 2011 · PLoS ONE
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    • "Currently, a combination of MLST using seven housekeeping genes together with sequence data from PorA, PorB and FetA is considered optimal for dissecting the diversity and dynamics of meningococcal populations (Urwin et al., 2004). For example, such fine-scale typing has been employed to evaluate the impact of mass immunization with a serogroup C vaccine on the risk of emergence of escape variants (Lancellotti et al., 2006), to characterize the risk of fatal MD (Jacobsson et al., 2008), to investigate outbreaks (Feavers et al., 1999) and to establish epidemiological links between cases (Elias et al., 2006). A sample of N. meningitidis isolates was collected in Cuba both before and after the introduction of VA-MENGOC-BC 1 and comprises isolates from both asymptomatic carriers and patients with meningococcal disease. "
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    ABSTRACT: We investigated the population genetics in collections of meningococci sampled in Cuba during the period 1983-2005, thereby covering a period before and after the introduction of an antimeningococcal B-C vaccine. A total of 163 case isolates and 210 isolates from healthy carriers were characterized by multilocus sequence typing (MLST) and sequence determination of porA, porB and fetA genes. A total of 56 sequence types (STs) including 28 new STs were identified among these isolates. The analysis of surface antigens revealed variants 3-1 and 3-8 to be prevalent for porB; variant F5-1 was the most common FetA epitope, and variants 19 and 15 corresponded to the prevalent variable regions 1 (VR1) and VR2 PorA epitopes, respectively. The strongest associations between specific surface protein variants and clonal complexes were detected in lineages ST-32 and ST-53. All ST-32 complex isolates possessed porB3 alleles, and the most frequent antigen combination among ST-32 complex isolates was P1.19,15;F5-1. Variants PorB3-64 at PorB and P1.30 at PorA VR2, in combination with the PorA VR1 variants P1.12-1, P1.7 and P1.7-2 as well as the FetA variants F1-2 and F1-7, dominated the ST-53 complex organisms. Furthermore, we observed a statistically significant association between the most frequent porA, porB and fetA alleles and strain invasiveness. Finally, this study showed that the application of VA-MENGOC-BC((R)), the Cuban antimeningococcal vaccine, reduced the number and frequency of the hypervirulent Clonal Complexes ST-32 and ST-41/44, and also impacted on other lineages. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST.
    Full-text · Article · Feb 2010 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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