Characteristics of Neisseria meningitidis isolates causing fatal disease.
ABSTRACT 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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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.Expert Review of Hematology 02/2009; 2(1):7-16. DOI:10.1586/17474086.2.1.7
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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.Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 02/2010; 10(4):546-54. DOI:10.1016/j.meegid.2010.02.002