Dataset Information

Prevalence and clinical course in invasive infections with meningococcal endotoxin variants.

ABSTRACT:

Background

Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.

Methods

A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The lpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records.

Results

Of 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95%CI 0.09-0.58) and were less often admitted to intensive care (OR 0.21; 95%CI 0.07-0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics.

Conclusions

In adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course.

SUBMITTER: Rodenburg GD

PROVIDER: S-EPMC3510230 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prevalence and clinical course in invasive infections with meningococcal endotoxin variants.

Rodenburg Gerwin D GD Fransen Floris F Bogaert Debby D Schipper Kim K Groenwold Rolf H H RH Hamstra Hendrik Jan HJ Westerhuis Brenda M BM van de Beek Diederik D van der Ley Peter P Sanders Elisabeth A M EA van der Ende Arie A

PloS one 20121129 11

<h4>Background</h4>Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.<h4>Methods</h4>A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono ...[more]

PMID: 23209568

Similar Datasets

Project description:Anaplasma phagocytophilum is an obligate intracellular, tick-transmitted bacterium that causes granulocytic anaplasmosis in humans and several mammalian species including domestic ruminants where it is called tick-borne fever (TBF). Different genetic variants exist but their impact with regard to putative differences in host associations and pathogenicity are not yet completely understood.Natural infections with A. phagocytophilum in a dairy cattle herd in Germany were investigated over one pasture season by using serology, haematology, blood chemistry and polymerase chain reaction (PCR). Sequence analysis of partial 16S rRNA, groEL, msp2 and msp4 genes of A. phagocytophilum was carried out in order to trace possible genetic variants and their relations between cattle, roe deer (Capreolus capreolus) and ticks (Ixodes ricinus) in this area.In total 533 samples from 58 cattle, 310 ticks, three roe deer and one wild boar were examined. Our results show (i) typical clinical symptoms of TBF in first-time infected heifers, such as high fever, reduced milk yield, lower limb oedema and typical haematological and biochemical findings such as severe leukopenia, erythropenia, neutropenia, lymphocytopenia, monocytopenia, a significant increase in creatinine and bilirubin and a significant decrease in serum albumin, ?-GT, GLDH, magnesium and calcium; (ii) a high overall prevalence of A. phagocytophilum infections in this herd as 78.9% (15/19) of the naïve heifers were real-time PCR-positive and 75.9% (44/58) of the entire herd seroconverted; and (iii) a high level of sequence variation in the analysed genes with five variants of the 16S rRNA gene, two variants of the groEL gene, three variants of the msp2 gene and four variants in the msp4 gene with certain combinations of these variants.In cattle particular combinations of the genetic variants of A. phagocytophilum occurred, whereas three roe deer showed different variants altogether. This is indicative for a sympatric circulation of variants in this small geographical region (< 1 km2). Both re- and superinfections with A. phagocytophilum were observed in five cattle showing that infection does not result in sterile immunity. For prevention of clinical cases we suggest pasturing of young, not pregnant heifers to reduce economical losses.

Project description:BACKGROUND:Limited data is available to describe clinical characteristics, long-term outcomes, healthcare resource use and the attributable costs of invasive meningococcal disease (IMD) in Germany. We aimed to examine demographic and clinical characteristics as well as healthcare resource use and related costs. METHODS:We conducted a retrospective cohort study based on the InGef database in patients with IMD between 2009 and 2015. Cases were identified based on hospital main discharge diagnoses of IMD. Demographics, clinical characteristics, 30-day and 1-year mortality as well as IMD-related complications and sequelae in IMD cases were examined. In addition, short and long-term costs and healthcare resource use in IMD cases were analyzed and compared to an age- and sex-matched control group without IMD. RESULTS:The study population comprised 164 IMD cases between 2009 and 2015. The mean length of the IMD-related hospitalization was 13 days and 38% of all cases presented with meningitis only, 35% with sepsis only, 16% with both and 11% with other IMD. The 30-day and one-year mortality were 4.3% and 5.5%, respectively. Approximately 13% of IMD cases had documented IMD-related complications at hospital discharge and 24% suffered from sequelae during follow-up. The IMD-related hospitalization was associated with mean costs of € 9,620 (standard deviation: € 22,197). The difference of mean costs between IMD cases and matched non-IMD controls were € 267 in the first month and € 1,161 from one month to one year after discharged from IMD-related hospitalization. During the later follow-up period, the mean overall costs and costs associated with individual healthcare sectors were also higher for IMD cases without reaching statistical significance. CONCLUSIONS:IMD resulted in severe complications and sequelae and was associated with extensive costs and increased healthcare resource use in Germany, especially in the first year after IMD diagnosis and due the IMD-related hospitalization.

Dataset Information

Prevalence and clinical course in invasive infections with meningococcal endotoxin variants.

Background

Methods

Results

Conclusions

Publications

Prevalence and clinical course in invasive infections with meningococcal endotoxin variants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure