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.
"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 , improvements in clinical management , , and the introduction of the meningococcal C conjugate vaccine . 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 , , . "
[Show abstract][Hide abstract] 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.
PLoS ONE 10/2011; 6(10):e25957. DOI:10.1371/journal.pone.0025957 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening and debilitating disorder of hematopoiesis. The only curative treatment is allogeneic stem cell transplantation. Other treatments are generally supportive in nature. Recently, eculizumab, as a targeted, disease-modifying treatment, was approved by the US FDA and the European Commission. Eculizumab is a humanized monoclonal antibody that inhibits complement factor C5. It is the first approved drug that specifically inhibits complement. This article presents the major aspects of PNH that are necessary to understand the mechanism of action of eculizumab. Experience from the pilot study and the Phase III pivotal program of eculizumab in PNH will be summarized and the impact of eculizumab on the future treatment of PNH will be discussed.
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