Community-Acquired Bacterial Meningitis in Alcoholic Patients

BACKGROUND: Alcoholism is associated with susceptibility to infectious disease, particularly bacterial pneumonia. In the present study we described characteristics in alcoholic patients with bacterial meningitis and delineate the differences with findings in non-alcoholic adults with bacterial meningitis. METHODS/PRINCIPAL FINDINGS: This was a prospective nationwide observational cohort study including patients aged >16 years who had bacterial meningitis confirmed by culture of cerebrospinal fluid (696 episodes of bacterial meningitis occurring in 671 patients). Alcoholism was present in 27 of 686 recorded episodes of bacterial meningitis (4%) and alcoholics were more often male than non-alcoholics (82% vs 48%, P = 0.001). A higher proportion of alcoholics had underlying pneumonia (41% vs 11% P<0.001). Alcoholics were more likely to have meningitis due to infection with Streptococcus pneumoniae (70% vs 50%, P = 0.01) and Listeria monocytogenes (19% vs 4%, P = 0.005), whereas Neisseria meningitidis was more common in non-alcoholic patients (39% vs 4%, P = 0.01). A large proportion of alcoholics developed complications during clinical course (82% vs 62%, as compared with non-alcoholics; P = 0.04), often cardiorespiratory failure (52% vs 28%, as compared with non-alcoholics; P = 0.01). Alcoholic patients were at risk for unfavourable outcome (67% vs 33%, as compared with non-alcoholics; P<0.001). CONCLUSIONS/SIGNIFICANCE: Alcoholic patients are at high risk for complications resulting in high morbidity and mortality. They are especially at risk for cardiorespiratory failure due to underlying pneumonia, and therefore, aggressive supportive care may be crucial in the treatment of these patient

Identification of a novel anti-σE factor in Neisseria meningitidis

<p>Abstract</p> <p>Background</p> <p>Fine tuning expression of genes is a prerequisite for the strictly human pathogen <it>Neisseria meningitidis </it>to survive hostile growth conditions and establish disease. Many bacterial species respond to stress by using alternative σ factors which, in complex with RNA polymerase holoenzyme, recognize specific promoter determinants. σ^E, encoded by <it>rpoE </it>(NMB2144) in meningococci, is known to be essential in mounting responses to environmental challenges in many pathogens. Here we identified genes belonging to the σ^Eregulon of meningococci.</p> <p>Results</p> <p>We show that meningococcal σ^Eis part of the polycistronic operon NMB2140-NMB2145 and autoregulated. In addition we demonstrate that σ^Econtrols expression of methionine sulfoxide reductase (MsrA/MsrB). Moreover, we provide evidence that the activity of σ^Eis under control of NMB2145, directly downstream of <it>rpoE</it>. The protein encoded by NMB2145 is structurally related to anti-sigma domain (ASD) proteins and characterized by a zinc containing anti-σ factor (ZAS) motif, a hall mark of a specific class of Zn^2+-binding ASD proteins acting as anti-σ factors. We demonstrate that Cys residues in ZAS, as well as the Cys residue on position 4, are essential for anti-σ^Eactivity of NMB2145, as found for a minority of members of the ZAS family that are predicted to act in the cytoplasm and responding to oxidative stimuli. However, exposure of cells to oxidative stimuli did not result in altered expression of σ^E.</p> <p>Conclusions</p> <p>Together, our results demonstrate that meningococci express a functional transcriptionally autoregulated σ^Efactor, the activity of which is controlled by a novel meningococcal anti-σ factor belonging to the ZAS family.</p

Two variants among Haemophilus influenzae serotype b strains with distinct bcs4, hcsA and hcsB genes display differences in expression of the polysaccharide capsule

<p>Abstract</p> <p>Background</p> <p>Despite nearly complete vaccine coverage, a small number of fully vaccinated children in the Netherlands have experienced invasive disease caused by <it>Haemophilus influenzae </it>serotype b (Hib). This increase started in 2002, nine years after the introduction of nationwide vaccination in the Netherlands. The capsular polysaccharide of Hib is used as a conjugate vaccine to protect against Hib disease. To evaluate the possible rise of escape variants, explaining the increased number of vaccine failures we analyzed the composition of the capsular genes and the expressed polysaccharide of Dutch Hib strains collected before and after the introduction of Hib vaccination.</p> <p>Results</p> <p>The DNA sequences of the complete capsular gene clusters of 9 Dutch Hib strains were assessed and two variants, designated type I and type II were found. The two variants displayed considerable sequence divergence in the <it>hcsA </it>and <it>hcsB </it>genes, involved in transport of capsular polysaccharide to the cell surface. Application of <it>hcsA </it>type specific PCRs on 670 Hib strains collected from Dutch patients with invasive Hib disease showed that 5% of the strains collected before 1996 were type II. No endogenous type II Hib strains were isolated after 1995 and all type II strains were isolated from 0–4 year old, non-vaccinated children only. Analysis of a worldwide collection of Hib strains from the pre-vaccination era revealed considerable geographic differences in the distribution of the type I and type II strains with up to 73% of type II strains in the USA. NMR analysis of type I and type II capsule polysaccharides did not reveal structural differences. However, type I strains were shown to produce twice as much surface bound capsular polysaccharide.</p> <p>Conclusion</p> <p>Type II strains were only isolated during the pre-vaccination era from young, non-vaccinated individuals and displayed a lower expression of capsular polysaccharide than type I strains. The higher polysaccharide expression may have provided a selective advantage for type I strains resulting in the rapid elimination of type II from the Dutch Hib population after introduction of nationwide Hib vaccination. However, this phenomenon does not explain the increase in the number of Hib vaccine failures in the Netherlands.</p

Compositional discordance between prokaryotic plasmids and host chromosomes

BACKGROUND: Most plasmids depend on the host replication machinery and possess partitioning genes. These properties confine plasmids to a limited range of hosts, yielding a close and presumably stable relationship between plasmid and host. Hence, it is anticipated that due to amelioration the dinucleotide composition of plasmids is similar to that of the genome of their hosts. However, plasmids are also thought to play a major role in horizontal gene transfer and thus are frequently exchanged between hosts, suggesting dinucleotide composition dissimilarity between plasmid and host genome. We compared the dinucleotide composition of a large collection of plasmids with that of their host genomes to shed more light on this enigma. RESULTS: The dinucleotide frequency, coined the genome signature, facilitates the identification of putative horizontally transferred DNA in complete genome sequences, since it was found to be typical for a certain genome, and similar between related species. By comparison of the genome signature of 230 plasmid sequences with that of the genome of each respective host, we found that in general the genome signature of plasmids is dissimilar from that of their host genome. CONCLUSION: Our results show that the genome signature of plasmids does not resemble that of their host genome. This indicates either absence of amelioration or a less stable relationship between plasmids and their host. We propose an indiscriminate lifestyle for plasmids preserving the genome signature discordance between these episomes and host chromosomes

Українська культура як чинник української державності: історичний аспект

У статті подано особливості формування української національної культури кінця XIX - XX століть. Охарактеризовано розвиток культури за умови становлення української державності. Автор намагався простежити вплив національного суспільства на розвиток культури в конкретний історичний період.The article introduces the features of formation of the Ukrainian national culture of the 19th-20th centuries. Characterized by the development of culture during becoming of Ukrainian statehood. The author tried to trace the influence of the national society for the development of culture in a specific historical period

Implementation of MenACWY vaccination because of ongoing increase in serogroup W invasive meningococcal disease, the Netherlands, 2018.

The annual incidence rate of serogroup W invasive meningococcal disease in the Netherlands increased from < 0.05/100,000 (n < 10) before 2015 to 0.5/100,000 (n = 80) in 2017. Most isolates (94%) belong to clonal complex 11. The incidence rate is highest among  < 5 year-olds and 15-24 year-olds. The case fatality rate was 12% (17/138) in 2015-2017. From May 2018, MenACWY vaccination replaces MenC vaccination at age 14 months and from October 2018, 13-14 year-olds are offered MenACWY vaccination

Genetic Variation in the β2-Adrenocepter Gene Is Associated with Susceptibility to Bacterial Meningitis in Adults

Recently, the biased β2-adrenoceptor/β-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the β2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective genetic association study we genotyped 542 patients with CSF culture proven community acquired bacterial meningitis and 376 matched controls for 2 functional single nucleotide polymorphisms in the β2-adrenoceptor gene (ADRB2). Furthermore, we analyzed if the use of non-selective beta-blockers, which bind to the β2-adrenoceptor, influenced the risk of bacterial meningitis. We identified a functional polymorphism in ADRB2 (rs1042714) to be associated with an increased risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI] 1.04–1.76; p = 0.026). The association remained significant after correction for age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95% CI 1.12–2.07; p = 0.007). For meningococcal meningitis the difference in genotype frequencies between patients and controls was similar to that in pneumococcal meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60–3.38; p = 0.72). Patients with bacterial meningitis had a lower frequency of non-selective beta-blockers use compared to the age matched population (0.9% vs. 1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88–4.39]; p = 0.09). In conclusion, we identified an association between a genetic variant in the β2-adrenoceptor and increased susceptibility to bacterial meningitis. The potential benefit of pharmacological treatment targeting the β2-adrenoceptor to prevent bacterial meningitis in the general population or patients with bacteraemia should be further studied in both experimental studies and observational cohorts

Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion

Group B Streptococcus (GBS), or Streptococcus agalactiae, is a pathogen that causes preterm births, stillbirths, and acute invasive neonatal disease burden and mortality. Here, we investigate bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease. We carry out a genome-wide association study (GWAS) of 1,338 GBS isolates from newborns with acute invasive disease; the isolates had been collected annually, for 30 years, through a national bacterial surveillance program in the Netherlands. After controlling for the population structure, we identify genetic variation within noncoding and coding regions, particularly the capsule biosynthesis locus, statistically associated with neonatal GBS disease onset time and meningeal invasion. Our findings highlight the impact of integrating microbial population genomics and clinical pathogen surveillance, and demonstrate the effect of GBS genetics on disease pathogenesis in neonates and infants

Multi locus sequence typing of Chlamydiales: clonal groupings within the obligate intracellular bacteria Chlamydia trachomatis

<p>Abstract</p> <p>Background</p> <p>The obligate intracellular growing bacterium <it>Chlamydia trachomatis </it>causes diseases like trachoma, urogenital infection and lymphogranuloma venereum with severe morbidity. Several serovars and genotypes have been identified, but these could not be linked to clinical disease or outcome. The related <it>Chlamydophila pneumoniae</it>, of which no subtypes are recognized, causes respiratory infections worldwide. We developed a multi locus sequence typing (MLST) scheme to understand the population genetic structure and diversity of these species and to evaluate the association between genotype and disease.</p> <p>Results</p> <p>A collection of 26 strains of <it>C. trachomatis </it>of different serovars and clinical presentation and 18 strains of <it>C. pneumoniae </it>were included in the study. For comparison, sequences of <it>C. abortus, C. psittaci</it>, <it>C. caviae</it>, <it>C. felis</it>, <it>C. pecorum </it>(<it>Chlamydophila</it>), <it>C. muridarum </it>(<it>Chlamydia</it>) and of <it>Candidatus protochlamydia </it>and <it>Simkania negevensis </it>were also included. Sequences of fragments (400 – 500 base pairs) from seven housekeeping genes (<it>enoA</it>, <it>fumC</it>, <it>gatA</it>, <it>gidA</it>, <it>hemN</it>, <it>hlfX</it>, <it>oppA</it>) were analysed. Analysis of allelic profiles by eBurst revealed three non-overlapping clonal complexes among the <it>C. trachomatis </it>strains, while the <it>C. pneumoniae </it>strains formed a single group. An UPGMA tree produced from the allelic profiles resulted in three groups of sequence types. The LGV strains grouped in a single cluster, while the urogenital strains were distributed over two separated groups, one consisted solely of strains with frequent occurring serovars (E, D and F). The distribution of the different serovars over the three groups was not consistent, suggesting exchange of serovar encoding <it>ompA </it>sequences. In one instance, exchange of <it>fumC </it>sequences between strains of different groups was observed. Cluster analyses of concatenated sequences of the Chlamydophila and Chlamydia species together with those of <it>Candidatus Protochlamydia amoebophila </it>and <it>Simkania negevensis </it>resulted in a tree identical to that obtained with 23S RNA gene sequences.</p> <p>Conclusion</p> <p>These data show that <it>C. trachomatis </it>and <it>C. pneumoniae </it>are highly uniform. The difference in genetic diversity between <it>C. trachomatis </it>and <it>C. pneumoniae </it>is in concordance with a later assimilation to the human host of the latter. Our data supports the taxonomy of the order of <it>Chlamydiales</it>.</p