Analysis of the ontogeny of the murine humoral response to Neisseria meningitidis B capsular polysaccharide reveals levels of complexity relevant to vaccine development.

PubMed

Colino, J; Outschoorn, I

2001-12-15

Although purified capsular polysaccharide of Neisseria meningitidis group B (CpsB) is not immunogenic at any age, CpsB on the bacterial surface elicits antibody responses late in ontogeny. Therefore, a detailed analysis of the ontogeny of the murine anti-CpsB response to N. meningitidis could determine key parameters regarding the poor immunogenicity of CpsB. The effects of bacterial dose, hyperimmunization, age, and sex on the induction of primary and secondary anti-CpsB immunoglobulin isotype profiles were studied. It was demonstrated that the timing and repetition of immunization and of the bacterial dose have a marked differential effect on the primary induction of anti-CpsB immunoglobulin isotypes and on the ability to induce anti-CpsB antibody responses after subsequent rechallenge. It is noteworthy that the ontogeny of the response is related to the appearance of natural anti-CpsB antibodies, but this is not associated with the presence of CpsB cross-reactive antigens in the microflora.

In silico analysis of different generation β lactams antibiotics with penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal disease.

PubMed

Tripathi, Vijay; Tripathi, Pooja; Srivastava, Navita; Gupta, Dwijendra

2014-12-01

Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2 (PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N. meningitidis and these are the target for β-lactam antibiotics. For many years penicillin has been recognized as the antibiotic for meningococcal disease but the meningococcus has seemed to be antibiotic resistance. In the present work we have verified the molecular interaction of Penicillin binding protein-2 N. meningitidis to different generation of β-lactam antibiotics and concluded that the third generation of β-lactam antibiotics shows efficient binding with Penicillin binding protein-2 of N. meningitidis. On the basis of binding efficiency and inhibition constant, ceftazidime emerged as the most efficient antibiotic amongst the other advanced β-lactam antibiotics against Penicillin-binding protein-2 of N. meningitidis.

Production of polyclonal and monoclonal antibodies against group A, B, and C capsular polysaccharides of Neisseria meningitidis and preparation of latex reagents.

PubMed Central

Nato, F; Mazie, J C; Fournier, J M; Slizewicz, B; Sagot, N; Guibourdenche, M; Postic, D; Riou, J Y

1991-01-01

Polyclonal and monoclonal antibodies against capsular polysaccharides of Neisseria meningitidis serogroups A, B, and C were produced in order to develop immunological reagents allowing both the detection of soluble antigens during meningococcal meningitis and antigenic serogrouping of N. meningitidis cultures. The performance characteristics of monoclonal and polyclonal antibody latex reagents were compared. For the detection of soluble polysaccharide antigen, polyclonal antibody latex reagent was selected for N. meningitidis A and C. The latex reagent prepared with polyclonal antibodies against N. meningitidis B could not detect capsular polysaccharide even at 1 mg/ml. The monoclonal antibody B latex reagent which detected 100 ng of polysaccharide per ml was therefore chosen. For the serogroup identification of N. meningitidis, the use of a confirmatory test results in an overall specificity of 100% with polyclonal or monoclonal antibody latex reagents. PMID:1909346

Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes

PubMed Central

Baart, Gino JE; Zomer, Bert; de Haan, Alex; van der Pol, Leo A; Beuvery, E Coen; Tramper, Johannes; Martens, Dirk E

2007-01-01

Background Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years. Results Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested succesfully in batch and chemostat cultures. Conclusion The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature. PMID:17617894

[Epidemic meningitis in 2013 in Republic of Guinea: Nesseria meningitidis W135 emergence].

PubMed

Traoré, F A; Sako, F B; Sylla, D; Kader, D S; Bangoura, M; Traoré, M; Keita, A; Sidibé, A; Keita, S; Barry, M; Cisse, M; Touré, A

2016-12-01

A prospective study conducted from 1 January to 31 December 2013 described a meningitis epidemic in Republic of Guinea. The identification of the germs was based on Gram stain, latex agglutination and culture. During the study period, 480 suspected cases of meningitis were reported by 21 health districts. The average age was 18±8 years and 62.5% were men. The vaccination status was unknown in all patients. The largest attack rates were found in Siguiri (3.2 per 10,000), Kankan (2.6 per 10,000) and Dabola (3.9 per 10,000). The locality of Kintinian in Siguiri was the only one to cross the epidemic threshold. The identified microorganisms were Haemophilus influenzae (1 time), Pneumococcus (2 times), Neisseria meningitidis A (4 times) and W135 (10 times) with a total of 17 positive samples. All of these germs were sensitive to chloramphenicol, ceftriaxone and ciprofloxacin. The average hospital stay was 6.5±2 days. The lethality was 13.8%. This meningitis epidemic was characterized by the emergence of Neisseria meningitidis W135. The monitoring of this serogroup should be increased and future vaccination strategies must include it presence.

Conformational studies of the capsular polysaccharide produced by Neisseria meningitidis group A.

PubMed

Foschiatti, Michela; Hearshaw, Meredith; Cescutti, Paola; Ravenscroft, Neil; Rizzo, R

2009-05-12

The effect of different cations on the conformational and morphological properties of the capsular polysaccharide produced by Neisseria meningitidis group A was investigated. Circular dichroism studies showed that the presence of Na(+), NH4+ or Ca(2+) ions induced different local conformations of the polysaccharide chain through interactions with the phosphodiester group bridging the saccharide residues in the polymer chain. Atomic force microscopy experiments confirmed that the morphology of the polysaccharide chains was different depending on the nature of the counterion. Ammonium ions were associated with the presence of single polymer chains in an elongated conformation, whereas sodium ions favored the folding of the chains into a globular conformation. The addition of calcium ions produced the aggregation of a limited number of globular polysaccharide chains to form a 'toroidal-like' structure.

Structural, functional and immunogenic insights on Cu,Zn Superoxide Dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

USDA-ARS?s Scientific Manuscript database

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and he...

Nitric Oxide Metabolism in Neisseria meningitidis

PubMed Central

Anjum, Muna F.; Stevanin, Tânia M.; Read, Robert C.; Moir, James W. B.

2002-01-01

Neisseria meningitidis, the causative agent of meningococcal disease in humans, is likely to be exposed to nitrosative stress during natural colonization and disease. The genome of N. meningitidis includes the genes aniA and norB, predicted to encode nitrite reductase and nitric oxide (NO) reductase, respectively. These gene products should allow the bacterium to denitrify nitrite to nitrous oxide. We show that N. meningitidis can support growth microaerobically by the denitrification of nitrite via NO and that norB is required for anaerobic growth with nitrite. NorB and, to a lesser extent, the cycP gene product cytochrome c′ are able to counteract toxicity due to exogenously added NO. Expression of these genes by N. meningitidis during colonization and disease may confer protection against exogenous or endogenous nitrosative stress. PMID:12003939

Development of a DNA Aptamer for Screening Neisseria meningitidis Serogroup B by Cell SELEX

PubMed Central

Mirzakhani, Kimia; Gargari, Seyed Latif Mousavi; Rasooli, Iraj; Rasoulinejad, Samaneh

2018-01-01

Background: Artificial oligonucleotides like DNA or RNA aptamers can be used as biodiagnostic alternatives for antibodies to detect pathogens. Comparing to antibodies, artificial oligonucleotides are produced easily at lower costs and are more stable. Neisseria meningitidis, the causative agent of meningitis, is responsible for about 1% of infections in an epidemic period. Specific DNA aptamers that bind to N. meningitidis serogroup B were identified by whole-cell Systemic Evolution of Ligands by EXponential Enrichment (SELEX). Methods: The SELEX begins with a library of labeled ssDNA molecules. After six rounds of selection and two rounds of counter-selection, 60 clones were obtained, of which the binding efficiency of 21 aptamers to the aforementioned bacterium was tested by flow cytometry. Results: The aptamers K3 and K4 showed the highest affinity to N. meningitidis serogroup B and no affinity to N. meningitidis serogroups Y, A, and C, or to other meningitis causing bacteria. The dissociation constant (Kd value) for K3 and K4 were calculated as 28.3 ± 8.9 pM and 39.1 ± 8.6 pM, respectively. K3 aptamer with the lowest Kd was chosen as the main aptamer. K3 could detect N. meningitidis in patients’ cerebrospinal fluid (CSF) samples and in CSF from healthy volunteers inoculated with N. meningitidis serogroup B (ATCC 13090) at 200 and 100 CFU ml-1, respectively. Conclusion: The findings suggest the application of the developed aptamer in specific detection of N. meningitidis serogroup B amongst a group of meningitis causing bacteria.

Differential Activation of Acid Sphingomyelinase and Ceramide Release Determines Invasiveness of Neisseria meningitidis into Brain Endothelial Cells

PubMed Central

Simonis, Alexander; Hebling, Sabrina; Gulbins, Erich; Schneider-Schaulies, Sibylle; Schubert-Unkmeir, Alexandra

2014-01-01

The interaction with brain endothelial cells is central to the pathogenicity of Neisseria meningitidis infections. Here, we show that N. meningitidis causes transient activation of acid sphingomyelinase (ASM) followed by ceramide release in brain endothelial cells. In response to N. meningitidis infection, ASM and ceramide are displayed at the outer leaflet of the cell membrane and condense into large membrane platforms which also concentrate the ErbB2 receptor. The outer membrane protein Opc and phosphatidylcholine-specific phospholipase C that is activated upon binding of the pathogen to heparan sulfate proteoglycans, are required for N. meningitidis-mediated ASM activation. Pharmacologic or genetic ablation of ASM abrogated meningococcal internalization without affecting bacterial adherence. In accordance, the restricted invasiveness of a defined set of pathogenic isolates of the ST-11/ST-8 clonal complex into brain endothelial cells directly correlated with their restricted ability to induce ASM and ceramide release. In conclusion, ASM activation and ceramide release are essential for internalization of Opc-expressing meningococci into brain endothelial cells, and this segregates with invasiveness of N. meningitidis strains. PMID:24945304

Epidemiology and diagnostic testing for meningitis in adults as the meningococcal epidemic declined at Middlemore Hospital.

PubMed

McBride, Stephen; Fulke, Jennifer; Giles, Hannah; Hobbs, Mark; Suh, Jun; Sathyendran, Vani; Thompson, Emily; Taylor, Susan; Holland, David

2015-03-13

To describe changes in epidemiology and diagnostic techniques for adult meningitis at Middlemore Hospital following the decline of the meningococcal epidemic. Retrospective audit of cases of meningitis from 2000 to 2009. Microbiologically-confirmed diagnosis (MCD) was established in 296 of 743 episodes (40%), most commonly enterovirus (123/296, 42%), Neisseria meningitidis (43/296, 15%) and Streptococcus pneumoniae (34/296, 11%). N. meningitidis meningitis declined and herpes viruses increased over time, without significant change in overall meningitis case numbers. By 2009, S. pneumoniae constituted a greater proportion of cases than N. meningitidis. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) and pneumococcal immunochromatographic testing (PICT) increased over time as did the proportion of cases with MCD. CSF Gram stain was positive in 45% (53/118) and CSF culture made MCD in 37% (44/118) of confirmed bacterial episodes (CBE). PCR provided MCD in 59% (26/54) of CBE and 99% (168/170) of viral episodes. CSF PICT was tested in 76% (26/34) of S. pneumoniae meningitis (positive in 92% (24/26). As the epidemic waned, local incidence of meningococcal meningitis decreased without significant decreasing meningitis overall. Empiric treatment for meningitis in New Zealand adults should routinely include pneumococcal cover. Increased PCR testing increases MCD in meningitis.

Reduction in Neisseria meningitidis infection in Italy after Meningococcal C conjugate vaccine introduction: A time trend analysis of 1994–2012 series

PubMed Central

de Waure, Chiara; Miglietta, Alessandro; Nedovic, Darko; Mereu, Giovanna; Ricciardi, Walter

2016-01-01

The incidence of invasive meningococcal disease (IMD) in Italy is among the lowest in Europe. Meningococcal C conjugate vaccine (MCC) was introduced in 2005 for 12 months old infants. The aim of this study was to describe the epidemiology of IMD in Italy from 1994 to 2012 and to evaluate the impact of MCC introduction. Data about Neisseria meningitidis (N. meningitidis) cases were drawn from the National Surveillance of Invasive Bacterial Diseases. The average incidence of IMD during 1994–2012 in Italy was 0.36 per 100,000 (95%CI 0.30; 0.40). N. meningitidis B was the most frequent serogroup and infants less than 12 months old were the most affected. Joinpoint analysis showed a statistically significant reduction in the incidence of N. meningitidis C related IMD after MCC introduction: the Annual Percentage Change declined from 21.8 (95%CI 15.1; 28.9) in 1994–2005 to −19.9 (95%CI −28.2; −10.7) afterwards. No changes were observed with respect to N. meningitidis B related IMD. Poisson regression showed a statistically significant reduction in the incidence of IMD both associated to N. meningitidis C (Incidence Rate Ratio 0.33; 95%CI 0.29; 0.37) and due to all serogroups (Incidence Rate Ratio 0.70; 95%CI 0.65; 0.75) in the post-vaccination period compared to the pre-vaccination one. On the other hand, the incidence of N. meningitidis B related IMD did not decrease. Our results suggest that MCC had an impact in decreasing the incidence of N. meningitidis C related IMD. However, data on typing are incomplete and efforts are needed to make them available for studying the need and the impact of other meningococcal vaccines. PMID:26308192

Antigenic potential of a highly conserved Neisseria meningitidis lipopolysaccharide inner core structure defined by chemical synthesis.

PubMed

Reinhardt, Anika; Yang, You; Claus, Heike; Pereira, Claney L; Cox, Andrew D; Vogel, Ulrich; Anish, Chakkumkal; Seeberger, Peter H

2015-01-22

Neisseria meningitidis is a leading cause of bacterial meningitis worldwide. We studied the potential of synthetic lipopolysaccharide (LPS) inner core structures as broadly protective antigens against N. meningitidis. Based on the specific reactivity of human serum antibodies to synthetic LPS cores, we selected a highly conserved LPS core tetrasaccharide as a promising antigen. This LPS inner core tetrasaccharide induced a robust IgG response in mice when formulated as an immunogenic glycoconjugate. Binding of raised mouse serum to a broad collection of N. meningitidis strains demonstrated the accessibility of the LPS core on viable bacteria. The distal trisaccharide was identified as the crucial epitope, whereas the proximal Kdo moiety was immunodominant and induced mainly nonprotective antibodies that are responsible for lack of functional protection in polyclonal serum. Our results identified key antigenic determinants of LPS core glycan and, hence, may aid the design of a broadly protective immunization against N. meningitidis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fluorescent Amplified-Fragment Length Polymorphism Genotyping of Neisseria meningitidis Identifies Clones Associated with Invasive Disease

PubMed Central

Goulding, Jonathan N.; Hookey, John V.; Stanley, John; Olver, Will; Neal, Keith R.; Ala'Aldeen, Dlawer A. A.; Arnold, Catherine

2000-01-01

Fluorescent amplified-fragment length polymorphism (FAFLP), a genotyping technique with phylogenetic significance, was applied to 123 isolates of Neisseria meningitidis. Nine of these were from an outbreak in a British university; 9 were from a recent outbreak in Pontypridd, Glamorgan; 15 were from sporadic cases of meningococcal disease; 26 were from the National Collection of Type Cultures; 58 were carrier isolates from Ironville, Derbyshire; 1 was a disease isolate from Ironville; and five were representatives of invasive clones of N. meningitidis. FAFLP analysis results were compared with previously published multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) results. FAFLP was able to identify hypervirulent, hyperendemic lineages (invasive clones) of N. meningitidis as well as did MLST. PFGE did not discriminate between two strains from the outbreak that were classified as similar but distinct by FAFLP. The results suggest that high resolution of N. meningitidis for outbreak and other epidemiological analyses is more cost efficient by FAFLP than by sequencing procedures. PMID:11101599

Use of Variable-Number Tandem Repeats To Examine Genetic Diversity of Neisseria meningitidis

PubMed Central

Yazdankhah, Siamak P.; Lindstedt, Bjørn-Arne; Caugant, Dominique A.

2005-01-01

Repetitive DNA motifs with potential variable-number tandem repeats (VNTR) were identified in the genome of Neisseria meningitidis and used to develop a typing method. A total of 146 meningococcal isolates recovered from carriers and patients were studied. These included 82 of the 107 N. meningitidis isolates previously used in the development of multilocus sequence typing (MLST), 45 isolates recovered from different counties in Norway in connection with local outbreaks, and 19 serogroup W135 isolates of sequence type 11 (ST-11), which were recovered in several parts of the world. The latter group comprised isolates related to the Hajj outbreak of 2000 and isolates recovered from outbreaks in Burkina Faso in 2001 and 2002. All isolates had been characterized previously by MLST or multilocus enzyme electrophoresis (MLEE). VNTR analysis showed that meningococcal isolates with similar MLST or MLEE types recovered from epidemiologically linked cases in a defined geographical area often presented similar VNTR patterns while isolates of the same MLST or MLEE types without an obvious epidemiological link showed variable VNTR patterns. Thus, VNTR analysis may be used for fine typing of meningococcal isolates after MLST or MLEE typing. The method might be especially valuable for differentiating among ST-11 strains, as shown by the VNTR analyses of serogroup W135 ST-11 meningococcal isolates recovered since the mid-1990s. PMID:15814988

Conservation and Accessibility of an Inner Core Lipopolysaccharide Epitope of Neisseria meningitidis

PubMed Central

Plested, Joyce S.; Makepeace, Katherine; Jennings, Michael P.; Gidney, Margaret Anne J.; Lacelle, Suzanne; Brisson, J.-R.; Cox, Andrew D.; Martin, Adele; Bird, A. Graham; Tang, Christoph M.; Mackinnon, Fiona M.; Richards, James C.; Moxon, E. Richard

1999-01-01

We investigated the conservation and antibody accessibility of inner core epitopes of Neisseria meningitidis lipopolysaccharide (LPS) because of their potential as vaccine candidates. An immunoglobulin G3 murine monoclonal antibody (MAb), designated MAb B5, was obtained by immunizing mice with a galE mutant of N. meningitidis H44/76 (B.15.P1.7,16 immunotype L3). We have shown that MAb B5 can bind to the core LPS of wild-type encapsulated MC58 (B.15.P1.7,16 immunotype L3) organisms in vitro and ex vivo. An inner core structure recognized by MAb B5 is conserved and accessible in 26 of 34 (76%) of group B and 78 of 112 (70%) of groups A, C, W, X, Y, and Z strains. N. meningitidis strains which possess this epitope are immunotypes in which phosphoethanolamine (PEtn) is linked to the 3-position of the β-chain heptose (HepII) of the inner core. In contrast, N. meningitidis strains lacking reactivity with MAb B5 have an alternative core structure in which PEtn is linked to an exocyclic position (i.e., position 6 or 7) of HepII (immunotypes L2, L4, and L6) or is absent (immunotype L5). We conclude that MAb B5 defines one or more of the major inner core glycoforms of N. meningitidis LPS. These findings support the possibility that immunogens capable of eliciting functional antibodies specific to inner core structures could be the basis of a vaccine against invasive infections caused by N. meningitidis. PMID:10496924

Immunoresponses to Neisseria meningitidis epitopes: suppression of secondary response to phosphorylcholine is carrier specific.

PubMed Central

Faro, J; Seoane, R; Eiras, A; Lareo, I; Couceiro, J; Regueiro, B J

1986-01-01

Results of our previous work have shown that Neisseria meningitidis serogroup B M986 can induce a phosphorylcholine (PC)-specific plaque-forming cell immunoresponse in mice. Also, a single injection of a relatively low dose of meningococci in NBF1 female mice induced a priming time-dependent suppression on subsequent meningococcus challenge. This suppression was not due to switching to another class of immunoglobulin nor to the presence of a capsule on N. meningitidis. In this study we show that suppression induced by meningococcus is carrier specific. Furthermore, we offer evidence suggesting that the structure(s) on meningococcus that trigger this suppression is heat labile and different from the antigenic structure(s) recognized by the suppressed B cells. In addition, we found that there is a gradual increase in antibody secretion rates of N. meningitidis-induced anti-PC plaque-forming cells that correlates with N. meningitidis priming time. Rather unexpected was the fact that pretreatment of mice with PC-keyhole limpet hemocyanin (thymus-dependent antigen) had a great influence on the subsequent PC-specific immunoresponses induced by N. meningitidis and PC-coupled heat-inactivated meningococcus [PC-(NMB)HI], as shown by (i) a striking decrease in T15 idiotype expression, (ii) concomitant direct anti-PC plaque-forming cells reduction, (iii) switching to immunoglobulin G (N. meningitidis-induced immunoresponse) or immunoglobulin G plus immunoglobulin A [PC-(NMB)HI-induced immunoresponse], and (iv) a significant increase in heterogeneity of plaque-forming cell secretion rates. The possibility that N. meningitidis, PC-(NMB)HI, and PC-KLH stimulate B lymphocytes pertaining to three different subpopulations embedded in distinct regulatory circuits is discussed, with emphasis on the interrelationships between T-dependent and T-independent lymphocyte compartments. We focus on the possibility of the existence of high-level regulatory circuits in which lymphocyte subpopulations or sets of lymphocyte subpopulations with different requirements of activation are connected. PMID:2416688

First genome report on novel sequence types of Neisseria meningitidis: ST12777 and ST12778.

PubMed

Veeraraghavan, Balaji; Lal, Binesh; Devanga Ragupathi, Naveen Kumar; Neeravi, Iyyan Raj; Jeyaraman, Ranjith; Varghese, Rosemol; Paul, Miracle Magdalene; Baskaran, Ashtawarthani; Ranjan, Ranjini

2018-03-01

Neisseria meningitidis is an important causative agent of meningitis and/or sepsis with high morbidity and mortality. Baseline genome data on N. meningitidis, especially from developing countries such as India, are lacking. This study aimed to investigate the whole genome sequences of N. meningitidis isolates from a tertiary care centre in India. Whole-genome sequencing was performed using an Ion Torrent™ Personal Genome Machine™ (PGM) with 400-bp chemistry. Data were assembled de novo using SPAdes Genome Assembler v.5.0.0.0. Sequence annotation was performed through PATRIC, RAST and the NCBI PGAAP server. Downstream analysis of the isolates was performed using the Center for Genomic Epidemiology databases for antimicrobial resistance genes and sequence types. Virulence factors and CRISPR were analysed using the PubMLST database and CRISPRFinder, respectively. This study reports the whole genome shotgun sequences of eight N. meningitidis isolates from bloodstream infections. The genome data revealed two novel sequence types (ST12777 and ST12778), along with ST11, ST437 and ST6928. The virulence profile of the isolates matched their sequence types. All isolates were negative for plasmid-mediated resistance genes. To the best of our knowledge, this is the first report of ST11 and ST437 N. meningitidis isolates in India along with two novel sequence types (ST12777 and ST12778). These results indicate that the sequence types circulating in India are diverse and require continuous monitoring. Further studies strengthening the genome data on N. meningitidis are required to understand the prevalence, spread, exact resistance and virulence mechanisms along with serotypes. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD

NASA Astrophysics Data System (ADS)

Calmettes, Charles; Ing, Christopher; Buckwalter, Carolyn M.; El Bakkouri, Majida; Chieh-Lin Lai, Christine; Pogoutse, Anastassia; Gray-Owen, Scott D.; Pomès, Régis; Moraes, Trevor F.

2015-08-01

Invading bacteria from the Neisseriaceae, Acinetobacteriaceae, Bordetellaceae and Moraxellaceae families express the conserved outer-membrane zinc transporter zinc-uptake component D (ZnuD) to overcome nutritional restriction imposed by the host organism during infection. Here we demonstrate that ZnuD is required for efficient systemic infections by the causative agent of bacterial meningitis, Neisseria meningitidis, in a mouse model. We also combine X-ray crystallography and molecular dynamics simulations to gain insight into the mechanism of zinc recognition and transport across the bacterial outer-membrane by ZnuD. Because ZnuD is also considered a promising vaccine candidate against N. meningitidis, we use several ZnuD structural intermediates to map potential antigenic epitopes, and propose a mechanism by which ZnuD can maintain high sequence conservation yet avoid immune recognition by altering the conformation of surface-exposed loops.

Capture of Pb2+ and Cu2+ Metal Cations by Neisseria meningitidis-type Capsular Polysaccharides.

PubMed

Ghimire, Sujan; McCarthy, Pumtiwitt C

2018-05-05

Heavy metal pollution of water is a significant environmental and public health concern. Current biological strategies for heavy metal removal from water are performed using microbial biopolymers, including polysaccharides, that are already fully formed. This creates limitations in adapting polysaccharides to increase binding affinity for specific metals. We propose that altering the specificity of polysaccharide-producing enzymes could be beneficial to improving metal capture by modified polysaccharides. We assess binding of Cu 2+ and Pb 2+ metal cations to Neisseria meningitidis -type polysaccharides. All concentrations of metal cations tested were able to completely bind to colominic acid. This polymer is equivalent to the capsular polysaccharide of N. meningitidis serogroup B comprised of a homopolymer of negatively charged sialic acid. There was slightly less binding observed with N. meningitidis serogroup W, which contains repeating units of the neutral sugar galactose and sialic acid. Our work represents the first assessment of the metal-binding properties of these capsular polysaccharides. Future work will seek to optimize metal-binding with Neisseria meningitidis serogroup W polysaccharide.

Rapid Laboratory Identification of Neisseria meningitidis Serogroup C as the Cause of an Outbreak - Liberia, 2017.

PubMed

Patel, Jaymin C; George, Josiah; Vuong, Jeni; Potts, Caelin C; Bozio, Catherine; Clark, Thomas A; Thomas, Jerry; Schier, Joshua; Chang, Arthur; Waller, Jessica L; Diaz, Maureen H; Whaley, Melissa; Jenkins, Laurel T; Fuller, Serena; Williams, Desmond E; Redd, John T; Arthur, Ray R; Taweh, Fahn; Vera Walker, Yatta; Hardy, Patrick; Freeman, Maxwell; Katawera, Victoria; Gwesa, Gulu; Gbanya, Miatta Z; Clement, Peter; Kohar, Henry; Stone, Mardia; Fallah, Mosoka; Nyenswah, Tolbert; Winchell, Jonas M; Wang, Xin; McNamara, Lucy A; Dokubo, E Kainne; Fox, LeAnne M

2017-10-27

On April 25, 2017, a cluster of unexplained illness and deaths among persons who had attended a funeral during April 21-22 was reported in Sinoe County, Liberia (1). Using a broad initial case definition, 31 cases were identified, including 13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases each were from Grand Bassa and Monsterrado counties, respectively. On May 5, 2017, initial multipathogen testing of specimens from four fatal cases using the Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens. Subsequent testing using direct real-time polymerase chain reaction (PCR) confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N. meningitidis was detected in specimens from 11 of the 13 patients who died; no specimens were available from the other two fatal cases. On May 16, 2017, the National Public Health Institute of Liberia and the Ministry of Health of Liberia issued a press release confirming serogroup C meningococcal disease as the cause of this outbreak in Liberia.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005-2012 in Turkey. A multicenter prospective surveillance study.

PubMed

Ceyhan, Mehmet; Gürler, Nezahat; Ozsurekci, Yasemin; Keser, Melike; Aycan, Ahmet Emre; Gurbuz, Venhar; Salman, Nuran; Camcioglu, Yildiz; Dinleyici, Ener Cagri; Ozkan, Sengul; Sensoy, Gulnar; Belet, Nursen; Alhan, Emre; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Uzun, Hakan; Faik Oner, Ahmet; Kurugol, Zafer; Ali Tas, Mehmet; Aygun, Denizmen; Karadag Oncel, Eda; Celik, Melda; Yasa, Olcay; Akin, Fatih; Coşkun, Yavuz

2014-01-01

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005–2012 in Turkey

PubMed Central

Ceyhan, Mehmet; Gürler, Nezahat; Ozsurekci, Yasemin; Keser, Melike; Aycan, Ahmet Emre; Gurbuz, Venhar; Salman, Nuran; Camcioglu, Yildiz; Dinleyici, Ener Cagri; Ozkan, Sengul; Sensoy, Gulnar; Belet, Nursen; Alhan, Emre; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Uzun, Hakan; Faik Oner, Ahmet; Kurugol, Zafer; Ali Tas, Mehmet; Aygun, Denizmen; Oncel, Eda Karadag; Celik, Melda; Yasa, Olcay; Akin, Fatih; Coşkun, Yavuz

2014-01-01

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey. PMID:25483487

Clinical Validation of Multiplex Real-Time PCR Assays for Detection of Bacterial Meningitis Pathogens

PubMed Central

Theodore, M. Jordan; Mair, Raydel; Trujillo-Lopez, Elizabeth; du Plessis, Mignon; Wolter, Nicole; Baughman, Andrew L.; Hatcher, Cynthia; Vuong, Jeni; Lott, Lisa; von Gottberg, Anne; Sacchi, Claudio; McDonald, J. Matthew; Messonnier, Nancy E.; Mayer, Leonard W.

2012-01-01

Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA and serogroup-specific genes in the cap locus for N. meningitidis serogroups A, B, C, W135, X, and Y. However, the assay sensitivity for serogroups B, W135, and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays for serogroup B synD, W135 synG, and Y synF showed 100% specificity for detecting N. meningitidis species, with high sensitivity (serogroup B synD, 99% [75/76]; W135 synG, 97% [38/39]; and Y synF, 100% [66/66]). The lower limits of detection (LLD) were 9, 43, and 10 copies/reaction for serogroup B synD, W135 synG, and Y synF assays, respectively, a significant improvement compared to results for the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of (i) N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA (NHS assay); (ii) N. meningitidis serogroups A, W135, and X (AWX assay); and (iii) N. meningitidis serogroups B, C, and Y (BCY assay). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for the singleplex assay. Pairwise comparison of real-time PCR between multiplex and singleplex assays showed that cycle threshold values of the multiplex assay were similar to those for the singleplex assay. There were no substantial differences in sensitivity and specificity between these multiplex and singleplex real-time PCR assays. PMID:22170919

Clinical validation of multiplex real-time PCR assays for detection of bacterial meningitis pathogens.

PubMed

Wang, Xin; Theodore, M Jordan; Mair, Raydel; Trujillo-Lopez, Elizabeth; du Plessis, Mignon; Wolter, Nicole; Baughman, Andrew L; Hatcher, Cynthia; Vuong, Jeni; Lott, Lisa; von Gottberg, Anne; Sacchi, Claudio; McDonald, J Matthew; Messonnier, Nancy E; Mayer, Leonard W

2012-03-01

Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA and serogroup-specific genes in the cap locus for N. meningitidis serogroups A, B, C, W135, X, and Y. However, the assay sensitivity for serogroups B, W135, and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays for serogroup B synD, W135 synG, and Y synF showed 100% specificity for detecting N. meningitidis species, with high sensitivity (serogroup B synD, 99% [75/76]; W135 synG, 97% [38/39]; and Y synF, 100% [66/66]). The lower limits of detection (LLD) were 9, 43, and 10 copies/reaction for serogroup B synD, W135 synG, and Y synF assays, respectively, a significant improvement compared to results for the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of (i) N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA (NHS assay); (ii) N. meningitidis serogroups A, W135, and X (AWX assay); and (iii) N. meningitidis serogroups B, C, and Y (BCY assay). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for the singleplex assay. Pairwise comparison of real-time PCR between multiplex and singleplex assays showed that cycle threshold values of the multiplex assay were similar to those for the singleplex assay. There were no substantial differences in sensitivity and specificity between these multiplex and singleplex real-time PCR assays.

Evaluation of the line probe assay for the rapid detection of bacterial meningitis pathogens in cerebrospinal fluid samples from children.

PubMed

Soysal, Ahmet; Toprak, Demet Gedikbasi; Türkoğlu, Salih; Bakir, Mustafa

2017-01-11

The aim of this study is to compare the diagnostic performance of the line probe assay (LPA) with conventional multiplex polymerase chain reaction (PCR) for Streptococcus pneumoniae as well as real-time PCR for Neisseria meningitidis and Haemophilus influenzae type b (Hib) in cerebrospinal fluid (CSF) samples from children during the multicenter national surveillance of bacterial meningitis between the years 2006 and 2009 in Turkey. During the study period 1460 subjects were enrolled and among them 841 (57%) met the criteria for probable bacterial meningitis. The mean age of subjects was 51 ± 47 months (range, 1-212 months). We performed the line probe assay in 751 (89%) CSF samples of 841 probable bacterial meningitis cases, of whom 431 (57%) were negative, 127 (17%) were positive for S. pneumoniae, 53 (7%) were positive for H. influenzae type b, and 41 (5%) were positive for N. meningitidis. The LPA was positive in 19 of 23 (82%) S. pneumoniae samples, 4 of 6 (67%) N. meningitidis samples and 2 of 2 (100%) Hib samples in CSF culture-positive cases. The specificity of the LPA for all of S. pneumoniae, H. influenzae type b, and N. meningitidis was 88% (95% CI: 85-91%), when using the standard PCR as a reference. The specificity of LPA for each of S. pneumoniae, H. influenzae type b, and N. meningitidis was 93% (95% CI: 89-95%), 96% (95% CI: 94-98%), and 99% (95% CI: 97-99%), respectively. For all of S. pneumoniae, H. influenzae type b and N. meningitidis the sensitivity of the LPA was 76% (95% CI: 70-82%) and for each of S. pneumoniae, H. influenzae type b and N. meningitidis was 72% (95% CI:63-79%), 88% (95% CI: 73-95%), and 81% (95% CI:67-92%), respectively. The LPA assay can be used to detect common bacterial meningitis pathogens in CSF samples, but the assay requires further improvement.

Neisseria meningitidis causes cell cycle arrest of human brain microvascular endothelial cells at S phase via p21 and cyclin G2.

PubMed

Oosthuysen, Wilhelm F; Mueller, Tobias; Dittrich, Marcus T; Schubert-Unkmeir, Alexandra

2016-01-01

Microbial pathogens have developed several mechanisms to modulate and interfere with host cell cycle progression. In this study, we analysed the effect of the human pathogen Neisseria meningitidis on cell cycle in a brain endothelial cell line as well as in primary brain endothelial cells. We found that N.  Meningitidis causes an accumulation of cells in the S phase early at 3 and at 24 h post-infection that was paralleled by a decrease of cells in G2/M phase. Importantly, the outer membrane proteins of the colony opacity-associated (Opa) protein family as well as the Opc protein proved to trigger the accumulation of cells in the S phase. A focused cell cycle reverse transcription quantitative polymerase chain reaction-based array and integrated network analysis revealed changes in the abundance of several cell cycle regulatory mRNAs, including the cell cycle inhibitors p21(WAF1/CIP1) and cyclin G2. These alterations were reflected in changes in protein expression levels and/or relocalization in N. meningitidis-infected cells. Moreover, an increase in p21(WAF1/CIP1) expression was found to be p53 independent. Genetic ablation of p21(WAF1/CIP1) and cyclin G2 abrogated N. meningitidis-induced S phase accumulation. Finally, by measuring the levels of the biomarker 8-hydroxydeoxyguanosine and phosphorylation of the histone variant H2AX, we provide evidence that N. meningitidis induces oxidative DNA damage in infected cells. © 2015 John Wiley & Sons Ltd.

Neisseria meningitidis serogroup A capsular polysaccharide acetyltransferase, methods and compositions

DOEpatents

Stephens, David S [Stone Mountain, GA; Gudlavalleti, Seshu K [Kensington, MD; Tzeng, Yih-Ling [Atlanta, GA; Datta, Anup K [San Diego, CA; Carlson, Russell W [Athens, GA

2011-02-08

Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup A Neisseria meningitidis using the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.

Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

DOE PAGES

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; ...

2015-10-12

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

PubMed Central

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; Cabelli, Diane E.; Bruns, Cami K.; Belzer, Carol A.; Gorringe, Andrew R.; Langford, Paul R.; Tabatabai, Louisa B.; Kroll, J. Simon; Tainer, John A.

2015-01-01

ABSTRACT Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. PMID:26459556

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus.

PubMed

Pratt, Ashley J; DiDonato, Michael; Shin, David S; Cabelli, Diane E; Bruns, Cami K; Belzer, Carol A; Gorringe, Andrew R; Langford, Paul R; Tabatabai, Louisa B; Kroll, J Simon; Tainer, John A; Getzoff, Elizabeth D

2015-12-01

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor

PubMed Central

Evans, Nicholas J.; Harrison, Odile B.; Clow, Kirsten; Derrick, Jeremy P.; Feavers, Ian M.; Maiden, Martin C. J.

2010-01-01

Meningococcal disease caused by serogroup B Neisseria meningitidis remains an important health problem in many parts of the world, and there are currently no comprehensive vaccines. Poor immunogenicity, combined with immunological identity to human sialic acids, have hindered the development of a serogroup B conjugate vaccine, resulting in the development of alternative vaccine candidates, including many outer-membrane protein (OMP)-based formulations. However, the design of protein-based meningococcal vaccines is complicated by the high level of genetic and antigenic diversity of the meningococcus. Knowledge of the extent and structuring of this diversity can have implications for the use of particular proteins as potential vaccine candidates. With this in mind, the diversity of the meningococcal OMP HmbR was investigated among N. meningitidis isolates representative of major hyper-invasive lineages. In common with other meningococcal antigens, the genetic diversity of hmbR resulted from a combination of intraspecies horizontal genetic exchange and de novo mutation. Furthermore, genealogical analysis showed an association of hmbR genes with clonal complexes and the occurrence of two hmbR families, A and B. Three variable regions (VR1–VR3), located in loops 2, 3 and 4, were observed with clonal complex structuring of VR types. A minority of codons (3.9 %), located within putative surface-exposed loop regions of a 2D model, were under diversifying selection, indicating regions of the protein likely to be subject to immune attack. PMID:20150237

System Specificity of the TpsB Transporters of Coexpressed Two-Partner Secretion Systems of Neisseria meningitidis

PubMed Central

ur Rahman, Sadeeq

2013-01-01

The two-partner secretion (TPS) systems of Gram-negative bacteria consist of a large secreted exoprotein (TpsA) and a transporter protein (TpsB) located in the outer membrane. TpsA targets TpsB for transport across the membrane via its ∼30-kDa TPS domain located at its N terminus, and this domain is also the minimal secretory unit. Neisseria meningitidis genomes encode up to five TpsAs and two TpsBs. Sequence alignments of TPS domains suggested that these are organized into three systems, while there are two TpsBs, which raised questions on their system specificity. We show here that the TpsB2 transporter of Neisseria meningitidis is able to secrete all types of TPS domains encoded in N. meningitidis and the related species Neisseria lactamica but not domains of Haemophilus influenzae and Pseudomonas aeruginosa. In contrast, the TpsB1 transporter seemed to be specific for its cognate N. meningitidis system and did not secrete the TPS domains of other meningococcal systems. However, TpsB1 did secrete the TPS2b domain of N. lactamica, which is related to the meningococcal TPS2 domains. Apparently, the secretion depends on specific sequences within the TPS domain rather than the overall TPS domain structure. PMID:23222722

Olfactory Nerve—A Novel Invasion Route of Neisseria meningitidis to Reach the Meninges

PubMed Central

Sjölinder, Hong; Jonsson, Ann-Beth

2010-01-01

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival. PMID:21124975

Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

PubMed

Sjölinder, Hong; Jonsson, Ann-Beth

2010-11-18

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

[Analysis for protection rate and antibody levels of epidemic cerebrospinal meningitis among children aged between 3-23 months in Liuzhou, in 2012].

PubMed

Cui, X L; Wu, X; Li, M Q

2016-12-06

Objective: To understand the level of bactericidal antibodies against Neisseria meningitidis and their rate of protection in children aged between 3 and 23 months, in Liuzhou, in 2012. Methods: Convenience sampling was performed in Liujiang, Rong'an and Sanjiang Counties from May through August, 2012. The inclusion criteria for 603 subjects were: Children aged between 3 and 23 months; no history of meningococcal meningitis; no vaccination against Neisseria meningitidis serogroup C; more than 30 days from the last vaccination against Neisseria meningitidis serogroup A. Demographic information and immunization history of the subjects were obtained using questionnaires. Venous blood samples (2.0 ml each) were collected and levels of Neisseria meningitides antibodies determined using a Serum Bactericidal Assay (SBA). The geometric mean titer (GMT) of serum bacterial antibodies was positive when it was greater than or equal to 1∶2 and protective when greater than 1∶8. Chi-square and Fisher's exact tests were used to compare differences in the positive and protective rates of serum antibodies of Neisseria meningitidis serogroup A and Neisseria meningitidis serogroup C, among children with different demographic characteristics. Kruskal-Wallis H test was used to compare differences in the GMT of serum antibodies of Neisseria meningitidis serogroup A and Neisseria meningitidis serogroup C, among children with different demographic characteristics. Results: Of 603 subjects, 325 (53.9%) were female and 278 (46.1%) were male; 276 (45.8%), 143 (23.7%) and 184 (30.5%) subjects were administered, respectively, no treatment, 1 dose vaccine and 2 doses vaccine. The GMT of serum antibodies against group A Neisseria meningitidis was 1∶1.11, the positive rate was 7.6% (46) and the protective rate was 2.0% (12). The GMT of antibodies in children receiving 1 vaccine dose was 1∶1.16 and the protective rate was 3.5% (5), both values higher than those in children receiving 2 vaccine doses (GMT: 1∶1.2, protective rate: 3.5% (5)). However, these differences were not statistically significant (GMT: H =0.64, P= 0.728; protective rate: Fisher's exact test, P= 0.080). The GMT of antibodies in children receiving 1 and 2 doses of meningococcal polysaccharide vaccines were 1∶1.12 and 1∶2.30, respectively (≤180 d). The GMT of serum antibodies for group C meningococcal vaccine was 1∶1.18 and its positive and protective rates were 14.6% (88) and 2.2% (13), respectively. Conclusion: Children aged between 3 and 23 months are susceptible to Neisseria meningitidis groups A and C. The immune effectiveness of group A meningococcal polysaccharide vaccine is relatively poor in this age group and their antibody levels decreased rapidly.

Using Single-Nucleotide Polymorphisms To Discriminate Disease-Associated from Carried Genomes of Neisseria meningitidis▿†

PubMed Central

Katz, Lee S.; Sharma, Nitya V.; Harcourt, Brian H.; Thomas, Jennifer Dolan; Wang, Xin; Mayer, Leonard W.; Jordan, I. King

2011-01-01

Neisseria meningitidis is one of the main agents of bacterial meningitis, causing substantial morbidity and mortality worldwide. However, most of the time N. meningitidis is carried as a commensal not associated with invasive disease. The genomic basis of the difference between disease-associated and carried isolates of N. meningitidis may provide critical insight into mechanisms of virulence, yet it has remained elusive. Here, we have taken a comparative genomics approach to interrogate the difference between disease-associated and carried isolates of N. meningitidis at the level of individual nucleotide variations (i.e., single nucleotide polymorphisms [SNPs]). We aligned complete genome sequences of 8 disease-associated and 4 carried isolates of N. meningitidis to search for SNPs that show mutually exclusive patterns of variation between the two groups. We found 63 SNPs that distinguish the 8 disease-associated genomes from the 4 carried genomes of N. meningitidis, which is far more than can be expected by chance alone given the level of nucleotide variation among the genomes. The putative list of SNPs that discriminate between disease-associated and carriage genomes may be expected to change with increased sampling or changes in the identities of the isolates being compared. Nevertheless, we show that these discriminating SNPs are more likely to reflect phenotypic differences than shared evolutionary history. Discriminating SNPs were mapped to genes, and the functions of the genes were evaluated for possible connections to virulence mechanisms. A number of overrepresented functional categories related to virulence were uncovered among SNP-associated genes, including genes related to the category “symbiosis, encompassing mutualism through parasitism.” PMID:21622743

Antimicrobial activity of LBM415 (NVP PDF-713) tested against pathogenic Neisseria spp. (Neisseria gonorrhoeae and Neisseria meningitidis).

PubMed

Jones, Ronald N; Sader, Helio S; Fritsche, Thomas R

2005-02-01

LBM415 (NVP PDF-713), a novel peptide deformylase inhibitor, was tested by reference methods against 2 collections of pathogenic Neisseria, N. gonorrhoeae (157 strains) and N. meningitidis (100 strains). The collection included strains resistant to penicillin, tetracycline, and fluoroquinolones and were also tested against ceftriaxone, ciprofloxacin, penicillin, and tetracycline. The 50% and 90% minimum inhibitory concentration values for LBM415 were 1 and 2 microg/mL, and 4 and 8 microg/mL for N. meningitidis and N. gonorrhoeae, respectively. All comparison agents were more active than this peptide deformylase inhibitor against this genus.

Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization

PubMed Central

Capel, Elena; Zomer, Aldert L.; Nussbaumer, Thomas; Bole, Christine; Izac, Brigitte; Frapy, Eric; Meyer, Julie; Bouzinba-Ségard, Haniaa; Bille, Emmanuelle; Jamet, Anne; Cavau, Anne; Letourneur, Franck; Bourdoulous, Sandrine; Rattei, Thomas; Coureuil, Mathieu

2016-01-01

ABSTRACT Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia, affecting infants and adults worldwide. N. meningitidis is also a common inhabitant of the human nasopharynx and, as such, is highly adapted to its niche. During bacteremia, N. meningitidis gains access to the blood compartment, where it adheres to endothelial cells of blood vessels and causes dramatic vascular damage. Colonization of the nasopharyngeal niche and communication with the different human cell types is a major issue of the N. meningitidis life cycle that is poorly understood. Here, highly saturated random transposon insertion libraries of N. meningitidis were engineered, and the fitness of mutations during routine growth and that of colonization of endothelial and epithelial cells in a flow device were assessed in a transposon insertion site sequencing (Tn-seq) analysis. This allowed the identification of genes essential for bacterial growth and genes specifically required for host cell colonization. In addition, after having identified the small noncoding RNAs (sRNAs) located in intergenic regions, the phenotypes associated with mutations in those sRNAs were defined. A total of 383 genes and 8 intergenic regions containing sRNA candidates were identified to be essential for growth, while 288 genes and 33 intergenic regions containing sRNA candidates were found to be specifically required for host cell colonization. PMID:27486197

Lysogeny and Bacteriocinogeny in Salmonella, Shigella, Bacillus Pyocyaneus and Neisseria meningitidis.

DTIC Science & Technology

1979-09-01

carriers and cerebro -spinal meningitis patients will be employed. Aooordin to the economic policy recently adopted by the Egyptia government, it has been...Nasr City, Cairo R. A E. III.- Neisaseiia meningitidis 19 strains of Neisseria menini-,itidis Group A isolated from patients’ throat or cerebro -spinal

Influence of Sodium Chloride on Growth of Neisseria meningitidis

PubMed Central

Mitzel, John R.; Hunter, Jack A.; Beam, Walter E.

1972-01-01

Nasopharyngeal isolates of Neisseria meningitidis were tested for growth on nutrient agar with and without the addition of 0.8% sodium chloride. Of the 822 strains tested, 1.3% grew on the salt-free medium, and 74.1% grew on the medium supplemented with sodium chloride. PMID:4626905

Meningococcal Neonatal Purulent Conjunctivitis/Sepsis and Asymptomatic Carriage of N. meningitidis in Mother's Vagina and Both Parents' Nasopharynx.

PubMed

Chacon-Cruz, Enrique; Alvelais-Palacios, Jorge Arturo; Rodriguez-Valencia, Jaime Alfonso; Lopatynsky-Reyes, Erika Zoe; Volker-Soberanes, Maria Luisa; Rivas-Landeros, Rosa Maria

2017-01-01

Neonatal conjunctivitis is usually associated with vagina's infection by Chlamydia sp., N. gonorrhoeae , and/or other bacteria during delivery. Meningococcal neonatal conjunctivitis is an extremely rare disease. We report a case of neonatal meningococcal sepsis/conjunctivitis and asymptomatic carriage of N. meningitidis from both parents (vagina and nasopharynx). As part of our active surveillance for meningococcal disease at the Tijuana General Hospital (TGH), Mexico, we identified a 3-day-old newborn with meningococcal conjunctivitis and sepsis. The patient had a one-day history of conjunctivitis and poor feeding. Clinical examination confirmed profuse purulent conjunctival discharge, as well as clinical signs and laboratory findings suggestive of bacteraemia. Gram stain from conjunctival exudate revealed intracellular Gram negative diplococci; we presumed the baby had gonorrheal conjunctivitis; however, serogroup Y, N. meningitidis was isolated both from conjunctival exudate and blood. Additionally, isolation of serogroup Y, N. meningitidis was obtained from mother's vagina and both parents' nasopharynx. The baby was treated with 7 days of IV ceftriaxone and discharged with no sequelae.

U.S. Military Fatalities due to Neisseria Meningitidis: Case Reports and Historical Perspective

DTIC Science & Technology

2011-03-01

Draper WH : Cerebro -spinal meningitis or spotted fever . Am Med Times 1864 ; 9: 99 – 101, 111–4 . 3. Jaeger H : Cerebrospinalmeningitis als...cer of the Board . In: Reports to the Local Government Board on Public Health and Medical Subjects, New Series no. 114, Further Reports on Cerebro ...2002 ; 35: 1376 – 81 . 18. Offi ce of the Surgeon General : Cerebro -spinal meningitis . In: Report of the Surgeon-General of the Army to the

A cross-sectional study assessing the pharyngeal carriage of Neisseria meningitidis in subjects aged 1-24 years in the city of Embu das Artes, São Paulo, Brazil.

PubMed

Weckx, Lily Yin; Puccini, Rosana Fiorini; Machado, Antónia; Gonçalves, Maria Gisele; Tuboi, Suely; de Barros, Eliana; Devadiga, Raghavendra; Ortega-Barria, Eduardo; Colindres, Romulo

Meningococcal carriage is a prerequisite for invasive infection. This cross-sectional study assessed the pharyngeal carriage prevalence in healthy subjects aged 1-24 years in Embu das Artes city, São Paulo, Brazil. Pharyngeal swabs were examined for the presence of Neisseria meningitidis. The isolates were tested for different serogroups using agglutination and polymerase chain reaction. A logistic regression model assessed any independent association between Neisseria meningitidis carriage and various risk factors. A total of 87/967 subjects (9%, 95% Confidence Interval (CI): 7.3-11.0) tested positive for N. meningitidis: 6.2% (95% CI: 3.8-9.4) in 1-4 years, 8.5% (95% CI: 5.1-13.0) in 5-9 years, 12.5% (95% CI: 7.8-18.6) in 10-14 years, 12.6% (95% CI: 7.4-19.7) in 15-19 years and 9% (95% CI: 4.9-14.9) in 20-24 years age groups. Highest carriage prevalence was observed in adolescents 10-19 years old. Serogroup C was predominant (18.4%) followed by serogroup B (12.6%). The 15-19 years age group showed a significant association between number of household members and carriers of N. meningitidis. This cross-sectional study is the first in Brazil to evaluate meningococcal carriage prevalence and associated factors in a wide age range. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England

PubMed Central

Giuliani, Marzia Monica; Biolchi, Alessia; Pizza, Mariagrazia; Beebeejaun, Kazim; Lucidarme, Jay; Findlow, Jamie; Ramsay, Mary E.; Borrow, Ray

2016-01-01

Serum samples from children immunized with a meningococcal serogroup B vaccine demonstrated potent serum bactericidal antibody activity against the hypervirulent Neisseria meningitidis serogroup W strain circulating in England. The recent introduction of this vaccine into the United Kingdom national immunization program should also help protect infants against this endemic strain. PMID:26811872

Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials.

PubMed

Bryant, Kristina; McVernon, Jodie; Marchant, Colin; Nolan, Terry; Marshall, Gary; Richmond, Peter; Marshall, Helen; Nissen, Michael; Lambert, Stephen; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline

2012-08-01

A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and VAR was demonstrated between groups and incidences of MMR- and VAR-specific solicited symptoms were similar, indicating that HibMenCY-TT can be coadministered with MMR and VAR.

[Moraxella osloensis as pathogen in septicemia (author's transl)].

PubMed

Fritsche, D; Karte, H; del Solar, E

1976-01-01

A case of septicemia caused by Moraxella osloensis is described. A 4-year old girl fell ill with symptoms similar to those described in cases of septicemia caused by Neisseria meningitidis. Two days after the commencement of treatment with penicillins, however, Moraxella osloensis could be isolated from cerebral fluid, which contained only a small number of cells. It is assumed that the delayed recovery of the child was directly related to the diminished susceptibility of this Moraxella strain to penicillins. Since Moraxella strains may be resistant to these antibiotics, it is necessary to distinguish between Moraxella and N. meningitidis by means of laboratory tests. The symptoms elicited by Moraxella are similar to those in septicaemia caused by N. meningitidis, but are considerably milder in character.

Prevalence of Neisseria meningitidis carriage: a small-scale survey in Istanbul, Turkey.

PubMed

Kepenekli Kadayifci, Eda; Güneşer Merdan, Deniz; Soysal, Ahmet; Karaaslan, Ayşe; Atıcı, Serkan; Durmaz, Rıza; Boran, Perran; Turan, İhsan; Söyletir, Güner; Bakır, Mustafa

2016-04-28

The human nasopharynx is the main reservoir of Neisseria meningitidis, and asymptomatic carriage is common. N. meningitidis one of the common causes of bacterial meningitis in Turkey, especially after the implementation of the national immunization program that includes conjugated pneumococcal and Haemophilus influenzae type b vaccines. The purpose of this study was to evaluate the prevalence of meningococcal carriage and determine the leading serogroup, which may help authorities to adapt appropriate meningococal vaccine into the national immunization programme. The prevalence of oropharyngeal carriage of N. meningitidis in 1,000 healthy subjects, 0-79 years of age, was investigated. Oropharyngeal swabs were collected during an 18-month period. Samples obtained were inoculated onto Thayer-Martin agar. The API-NH test and VITEK-MS system were used for identification of colonies. Multiplex real-time polymerase chain reaction assay was used to determine serogroups with serogroup-specific genes. N. meningitidis was isolated from 6 of 1,000 subjects (0.6%). Meningoccocal carriers were between 21 and 40 years of age. All isolates were serogrouped as B, except one that did not survive on subculture. N. lactamica was isolated from 13 of 1,000 subjects (1.3%). Carriage rate of meningococci in our study was relatively low. However, we detected that serogroup B was the leading strain in meningococcal carriage in Istanbul; choosing an appropriate meningococcal vaccine containing serogroup B should therefore be considered. High absolute humidity throughout the year in Istanbul may explain the low prevalence of carriage in our study. This should be verified with a multicenter national survey.

Cysteine Depletion Causes Oxidative Stress and Triggers Outer Membrane Vesicle Release by Neisseria meningitidis; Implications for Vaccine Development

PubMed Central

van de Waterbeemd, Bas; Zomer, Gijsbert; van den IJssel, Jan; van Keulen, Lonneke; Eppink, Michel H.; van der Ley, Peter; van der Pol, Leo A.

2013-01-01

Outer membrane vesicles (OMV) contain immunogenic proteins and contribute to in vivo survival and virulence of bacterial pathogens. The first OMV vaccines successfully stopped Neisseria meningitidis serogroup B outbreaks but required detergent-extraction for endotoxin removal. Current vaccines use attenuated endotoxin, to preserve immunological properties and allow a detergent-free process. The preferred process is based on spontaneously released OMV (sOMV), which are most similar to in vivo vesicles and easier to purify. The release mechanism however is poorly understood resulting in low yield. This study with N. meningitidis demonstrates that an external stimulus, cysteine depletion, can trigger growth arrest and sOMV release in sufficient quantities for vaccine production (±1500 human doses per liter cultivation). Transcriptome analysis suggests that cysteine depletion impairs iron-sulfur protein assembly and causes oxidative stress. Involvement of oxidative stress is confirmed by showing that addition of reactive oxygen species during cysteine-rich growth also triggers vesiculation. The sOMV in this study are similar to vesicles from natural infection, therefore cysteine-dependent vesiculation is likely to be relevant for the in vivo pathogenesis of N. meningitidis. PMID:23372704

Selective biotinylation of Neisseria meningitidis group B capsular polysaccharide and application in an improved ELISA for the detection of specific antibodies.

PubMed

Diaz Romero, J; Outschoorn, I

1993-03-15

A method is described for the selective biotinylation of meningococcal capsular polysaccharide from Neisseria meningitidis group B and its application to an enzyme-linked immunoabsorbent assay (ELISA) to detect specific antibodies by immobilization on streptavidin-coated microtiter wells. Capsular polysaccharide from Neisseria meningitidis B has been biotinylated by specific periodate oxidation of terminal residues and condensation of the resulting aldehydes with biotin hydrazide, using a spin-column technique in the intermediate purification steps. The ELISA was optimized employing an extended reaction time between the label alkaline phosphatase and its most common substrate, p-nitrophenyl phosphate, together with evaluation of blocking agents to minimize non-specific binding. Specificity was demonstrated by a direct competitive enzyme immunoassay (EIA).

Neisseria meningitidis colonization of the brain endothelium and cerebrospinal fluid invasion.

PubMed

Miller, Florence; Lécuyer, Hervé; Join-Lambert, Olivier; Bourdoulous, Sandrine; Marullo, Stefano; Nassif, Xavier; Coureuil, Mathieu

2013-04-01

The brain and meningeal spaces are protected from bacterial invasion by the blood-brain barrier, formed by specialized endothelial cells and tight intercellular junctional complexes. However, once in the bloodstream, Neisseria meningitidis crosses this barrier in about 60% of the cases. This highlights the particular efficacy with which N. meningitidis targets the brain vascular cell wall. The first step of central nervous system invasion is the direct interaction between bacteria and endothelial cells. This step is mediated by the type IV pili, which induce a remodelling of the endothelial monolayer, leading to the opening of the intercellular space. In this review, strategies used by the bacteria to survive in the bloodstream, to colonize the brain vasculature and to cross the blood-brain barrier will be discussed. © 2012 Blackwell Publishing Ltd.

Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras.

PubMed

Chen, Mingliang; Guo, Qinglan; Wang, Ye; Zou, Ying; Wang, Gangyi; Zhang, Xi; Xu, Xiaogang; Zhao, Miao; Hu, Fupin; Qu, Di; Chen, Min; Wang, Minggui

2015-06-01

Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC) prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis. A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84%) in 1965-1973 to serogroup A CC1 (58%) in 1974-1985, then to serogroup C or B CC4821 (62%) in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37) in 2005-2013 (p < 0.001). Among the ciprofloxacin-nonsusceptible isolates, 87% (27/31) were assigned to either CC4821 (n = 20) or CC5 (n = 7). The two predominant ciprofloxacin-resistant clones were designated ChinaCC4821-R1-C/B and ChinaCC5-R14-A. The ChinaCC4821-R1-C/B clone acquired ciprofloxacin resistance by a point mutation, and was present in 52% (16/31) of the ciprofloxacin-nonsusceptible disease isolates. The ChinaCC5-R14-A clone acquired ciprofloxacin resistance by horizontal gene transfer, and was found in 23% (7/31) of the ciprofloxacin-nonsusceptible disease isolates. The ciprofloxacin nonsusceptibility rate was 47% (7/15) among isolates from asymptomatic carriers, and nonsusceptibility was associated with diverse multi-locus sequence typing profiles and pulsed-field gel electrophoresis patterns. As detected after 2005, ciprofloxacin-nonsusceptible strains were shared between some of the patients and their close contacts. A limitation of this study is that isolates from 1986-2004 were not available and that only a small sample of convenience isolates from 1965-1985 were available. The increasing prevalence of ciprofloxacin resistance since 2005 in Shanghai was associated with the spread of hypervirulent lineages CC4821 and CC5. Two resistant meningococcal clones ChinaCC4821-R1-C/B and ChinaCC5-R14-A have emerged in Shanghai during the quinolone era. Ciprofloxacin should be utilized with caution for the chemoprophylaxis of N. meningitidis in China.

Meningococcal B Vaccination (4CMenB) in Infants and Toddlers

PubMed Central

Esposito, Susanna; Tagliabue, Claudia; Bosis, Samantha

2015-01-01

Neisseria meningitidis is a Gram-negative pathogen that actively invades its human host and leads to the development of life-threatening pathologies. One of the leading causes of death in the world, N. meningitidis can be responsible for nearly 1,000 new infections per 100,000 subjects during an epidemic period. The bacterial species are classified into 12 serogroups, five of which (A, B, C, W, and Y) cause the majority of meningitides. The three purified protein conjugate vaccines currently available target serogroups A, C, W, and Y. Serogroup B has long been a challenge but the discovery of the complete genome sequence of an MenB strain has allowed the development of a specific four-component vaccine (4CMenB). This review describes the pathogenetic role of N. meningitidis and the recent literature concerning the new meningococcal vaccine. PMID:26351647

Multicenter comparison of levels of antibody to the Neisseria meningitidis group A capsular polysaccharide measured by using an enzyme-linked immunosorbent assay.

PubMed Central

Carlone, G M; Frasch, C E; Siber, G R; Quataert, S; Gheesling, L L; Turner, S H; Plikaytis, B D; Helsel, L O; DeWitt, W E; Bibb, W F

1992-01-01

There is no standard immunoassay for evaluating immune responses to meningococcal vaccines. We developed an enzyme-linked immunosorbent assay to measure total levels of antibody to Neisseria meningitidis group A capsular polysaccharide. Five laboratories measured the antibody levels in six paired pre- and postvaccination serum samples by using the enzyme-linked immunosorbent assay. Methylated human serum albumin was used to bind native group A polysaccharide to microtiter plate surfaces. The between-laboratory coefficients of variation for pre- and postvaccination sera had ranges of 31 to 91 and 17 to 31, respectively. The mean laboratory coefficients of variation for pre- and postvaccination sera, respectively, were 17 and 11 (Molecular Biology Laboratory, Centers for Disease Control), 12 and 15 (Immunodiagnostic Methods Laboratory, Centers for Disease Control), 22 and 19 (Dana-Farber Cancer Institute), 38 and 38 (Bacterial Polysaccharide Laboratory, U.S. Food and Drug Administration), and 11 and 10 (Praxis Biologics, Inc.). Standardization of this enzyme-linked immunosorbent assay should allow interlaboratory comparison of meningococcal vaccine immunogenicity, thus providing a laboratory-based assessment tool for evaluating meningococcal vaccines. PMID:1734048

Outbreak of Neisseria meningitidis C in workers at a large food-processing plant in Brazil: challenges of controlling disease spread to the larger community.

PubMed

Iser, B P M; Lima, H C A V; de Moraes, C; de Almeida, R P A; Watanabe, L T; Alves, S L A; Lemos, A P S; Gorla, M C O; Gonçalves, M G; Dos Santos, D A; Sobel, J

2012-05-01

SUMMARYAn outbreak of meningococcal disease (MD) with severe morbidity and mortality was investigated in midwestern Brazil in order to identify control measures. A MD case was defined as isolation of Neisseria meningitidis, or detection of polysaccharide antigen in a sterile site, or presence of clinical purpura fulminans, or an epidemiological link with a laboratory-confirmed case-patient, between June and August 2008. In 8 out of 16 MD cases studied, serogroup C ST103 complex was identified. Five (31%) cases had neurological findings and five (31%) died. The attack rate was 12 cases/100 000 town residents and 60 cases/100 000 employees in a large local food-processing plant. We conducted a matched case-control study of eight primary laboratory-confirmed cases (1:4). Factors associated with illness in single variable analysis were work at the processing plant [matched odds ratio (mOR) 22, 95% confidence interval (CI) 2·3-207·7, P<0·01], and residing <1 year in Rio Verde (mOR 7, 95% CI 1·11-43·9, P<0·02). Mass vaccination (>10 000 plant employees) stopped propagation in the plant, but not in the larger community.

Community immunization programme in response to an outbreak of invasive Neisseria meningitidis serogroup C infection in the Trent region of England 1995-1996.

PubMed

Irwin, D J; Miller, J M; Milner, P C; Patterson, T; Richards, R G; Williams, D A; Insley, C A; Stuart, J M

1997-06-01

Between 8 December 1995 and 16 January 1996 seven laboratory confirmed cases of septicaemia owing to infection with Neisseria meningitidis serogroup C strains and one highly probable case of meningococcal septicaemia occurred in three electoral wards in south Rotherham and the Retford area of north Nottinghamshire. All cases occurred among children aged 1-17 years. One patient died. The public health response to this outbreak was the largest community prophylactic antibiotic and immunization programme against meningococcal infection, to date, in the United Kingdom. The target group for each Health Authority was 8900 for Rotherham Health Authorities and 8000 for North Nottinghamshire Health. Local logistical factors led to differences in the implementation of the programme by each Health Authority. At the completion of each programme, 8320 doses of vaccine had been administered (92.5 per cent coverage) during the Rotherham Health Authorities programme and 7660 (95.7 per cent coverage) during the North Nottinghamshire Health programme. The additional financial cost of the exercise amounted to approximately Pounds 125000 for each Health Authority. This paper describes the evolution of the outbreak, the decision-making process resulting in the immunization programme in each Health Authority, the implementation of each programme, problems identified and lessons learned.

Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis

PubMed Central

2010-01-01

Background Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. Results The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively. In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. Conclusions The PCR provides increased sensitivity and the multiplex format facilitates diagnosis of S. pneumoniae, H. influenzae and N. meningitidis and the assay enable detection after antibiotic treatment has been installed. Quantification increases the specificity of the etiology for pneumonia. PMID:21129171

Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

PubMed

Abdeldaim, Guma M K; Strålin, Kristoffer; Korsgaard, Jens; Blomberg, Jonas; Welinder-Olsson, Christina; Herrmann, Björn

2010-12-03

Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 10⁵ genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively.In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. The PCR provides increased sensitivity and the multiplex format facilitates diagnosis of S. pneumoniae, H. influenzae and N. meningitidis and the assay enable detection after antibiotic treatment has been installed. Quantification increases the specificity of the etiology for pneumonia.

Different meningitis-causing bacteria induce distinct inflammatory responses on interaction with cells of the human meninges.

PubMed

Fowler, Mark I; Weller, Roy O; Heckels, John E; Christodoulides, Myron

2004-06-01

The interactions of bacterial pathogens with cells of the human leptomeninges are critical events in the progression of meningitis. An in vitro model based on the culture of human meningioma cells was used to investigate the interactions of the meningeal pathogens Escherichia coli K1, Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. A rank order of association with meningioma cells was observed, with N. meningitidis showing the highest levels of adherence, followed by E. coli, S. pneumoniae and H. influenzae. Neisseria meningitidis and H. influenzae did not invade meningioma cells or induce cell death, but induced a concentration-dependent secretion of inflammatory mediators. Neisseria meningitidis induced higher levels of IL-6, MCP-1, RANTES and GM-CSF than H. influenzae, but there was no significant difference in the levels of IL-8 induced by both pathogens. Streptococcus pneumoniae was also unable to invade meningioma cells, but low concentrations of bacteria failed to stimulate cytokine secretion. However, higher concentrations of pneumococci led to cell death. By contrast, only E. coli K1 invaded meningioma cells directly and induced rapid cell death before an inflammatory response could be induced. These data demonstrate that the interactions of different bacterial pathogens with human meningeal cells are distinct, and suggest that different intervention strategies may be needed in order to prevent the morbidity and mortality associated with bacterial meningitis.

Genetic and Structural Characterization of L11 Lipooligosaccharide from Neisseria meningitidis Serogroup A Strains

PubMed Central

Mistretta, Noëlle; Seguin, Delphine; Thiébaud, Jerôme; Vialle, Sandrine; Blanc, Frédéric; Brossaud, Marina; Talaga, Philippe; Norheim, Gunnstein; Moreau, Monique; Rokbi, Bachra

2010-01-01

The lipooligosaccharide (LOS) of immunotype L11 is unique within serogroup A meningococci. In order to resolve its molecular structure, we conducted LOS genotyping by PCR analysis of genes responsible for α-chain sugar addition (lgtA, -B, -C, -E, -H, and -F) and inner core substituents (lgtG, lpt-3, and lpt-6). For this study, we selected seven strains belonging to subgroup III, a major clonal complex responsible for meningococcal meningitis epidemics in Africa. In addition, we sequenced the homopolymeric tract regions of three phase-variable genes (lgtA, lgtG, and lot-3) to predict gene functionality. The fine structure of the L11 LOS of each strain was determined using composition and glycosyl linkage analyses, NMR, and mass spectrometry. The masses of the dephosphorylated oligosaccharides were consistent with an oligosaccharide composed of two hexoses, one N-acetyl-hexosamine, two heptoses, and one KDO, as proposed previously. The molar composition of LOS showed two glucose residues to be present, in agreement with lgtH sequence prediction. Despite phosphoethanolaminetransferase genes lpt-3 and lpt-6 being present in all seven Neisseria meningitidis strains, phosphoethanolamine (PEtn) was found at both O-3 and O-6 of HepII among the three ST-5 strains, whereas among the four ST-7 strains, only one PEtn was found and located at O-3 of the HepII. The L11 LOS was found to be O-acetylated, as was indicated by the presence of the lot-3 gene being in-frame in all of the seven N. meningitidis strains. To our knowledge, these studies represent the first full genetic and structural characterization of the L11 LOS of N. meningitidis. These investigations also suggest the presence of further regulatory mechanisms affecting LOS structure microheterogeneity in N. meningitidis related to PEtn decoration of the inner core. PMID:20421293

Accuracy of real-time PCR, Gram stain and culture for Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae meningitis diagnosis.

PubMed

Wu, Henry M; Cordeiro, Soraia M; Harcourt, Brian H; Carvalho, Mariadaglorias; Azevedo, Jailton; Oliveira, Tainara Q; Leite, Mariela C; Salgado, Katia; Reis, Mitermayer G; Plikaytis, Brian D; Clark, Thomas A; Mayer, Leonard W; Ko, Albert I; Martin, Stacey W; Reis, Joice N

2013-01-22

Although cerebrospinal fluid (CSF) culture is the diagnostic reference standard for bacterial meningitis, its sensitivity is limited, particularly when antibiotics were previously administered. CSF Gram staining and real-time PCR are theoretically less affected by antibiotics; however, it is difficult to evaluate these tests with an imperfect reference standard. CSF from patients with suspected meningitis from Salvador, Brazil were tested with culture, Gram stain, and real-time PCR using S. pneumoniae, N. meningitidis, and H. influenzae specific primers and probes. An antibiotic detection disk bioassay was used to test for the presence of antibiotic activity in CSF. The diagnostic accuracy of tests were evaluated using multiple methods, including direct evaluation of Gram stain and real-time PCR against CSF culture, evaluation of real-time PCR against a composite reference standard, and latent class analysis modeling to evaluate all three tests simultaneously. Among 451 CSF specimens, 80 (17.7%) had culture isolation of one of the three pathogens (40 S. pneumoniae, 36 N. meningitidis, and 4 H. influenzae), and 113 (25.1%) were real-time PCR positive (51 S. pneumoniae, 57 N. meningitidis, and 5 H. influenzae). Compared to culture, real-time PCR sensitivity and specificity were 95.0% and 90.0%, respectively. In a latent class analysis model, the sensitivity and specificity estimates were: culture, 81.3% and 99.7%; Gram stain, 98.2% and 98.7%; and real-time PCR, 95.7% and 94.3%, respectively. Gram stain and real-time PCR sensitivity did not change significantly when there was antibiotic activity in the CSF. Real-time PCR and Gram stain were highly accurate in diagnosing meningitis caused by S. pneumoniae, N. meningitidis, and H. influenzae, though there were few cases of H. influenzae. Furthermore, real-time PCR and Gram staining were less affected by antibiotic presence and might be useful when antibiotics were previously administered. Gram staining, which is inexpensive and commonly available, should be encouraged in all clinical settings.

Estimating Costs Associated with a Community Outbreak of Meningococcal Disease in a Colombian Caribbean City

PubMed Central

Pinzón-Redondo, Hernando; Coronell-Rodriguez, Wilfrido; Díaz-Martinez, Inés; Guzmán-Corena, Ángel; Constenla, Dagna

2014-01-01

ABSTRACT Meningococcal disease is a serious and potentially life-threatening infection that is caused by the bacterium Neisseria meningitidis (N. meningitidis), and it can cause meningitis, meningococcaemia outbreaks and epidemics. The disease is fatal in 9-12% of cases and with a death rate of up to 40% among patients with meningococcaemia. The objective of this study was to estimate the costs of a meningococcal outbreak that occurred in a Caribbean city of Colombia. We contacted experts involved in the outbreak and asked them specific questions about the diagnosis and treatment for meningococcal cases during the outbreak. Estimates of costs of the outbreak were also based on extensive review of medical records available during the outbreak. The costs associated with the outbreak were divided into the cost of the disease response phase and the cost of the disease surveillance phase. The costs associated with the outbreak control and surveillance were expressed in US$ (2011) as cost per 1,000 inhabitants. The average age of patients was 4.6 years (SD 3.5); 50% of the cases died; 50% of the cases were reported to have meningitis (3/6); 33% were diagnosed with meningococcaemia and myocarditis (2/6); 50% of the cases had bacteraemia (3/6); 66% of the cases had a culture specimen positive for Neisseria meningitidis; 5 of the 6 cases had RT-PCR positive for N. meningitidis. All N. meningitidis were serogroup B; 50 doses of ceftriaxone were administered as prophylaxis. Vaccine was not available at the time. The costs associated with control of the outbreak were estimated at US$ 0.8 per 1,000 inhabitants, disease surveillance at US$ 4.1 per 1,000 inhabitants, and healthcare costs at US$ 5.1 per 1,000 inhabitants. The costs associated with meningococcal outbreaks are substantial, and the outbreaks should be prevented. The mass chemoprophylaxis implemented helped control the outbreak. PMID:25395916

Epidemiology and antibiotic resistance of bacterial meningitis in Dapaong, northern Togo.

PubMed

Karou, Simplice D; Balaka, Abago; Bamoké, Mitiname; Tchelougou, Daméhan; Assih, Maléki; Anani, Kokou; Agbonoko, Kodjo; Simpore, Jacques; de Souza, Comlan

2012-11-01

To assess the seasonality of the bacterial meningitis and the antibiotic resistance of incriminated bacteria over the last three years in the northern Togo. From January 2007 to January 2010, 533 cerebrospinal fluids (CSF) samples were collected from patients suspected of meningitis in the Regional Hospital of Dapaong (northern Togo). After microscopic examination, samples were cultured for bacterial identification and antibiotic susceptibility. The study included 533 patients (306 male and 227 female) aged from 1 day to 55 years [average age (13.00±2.07) years]. Bacterial isolation and identification were attempted for 254/533 (47.65%) samples. The bacterial species identified were: Neisseria meningitidis A (N. meningitidis A) (58.27%), Neisseria meningitidis W135 (N. meningitidis W135) (7.09%), Streptococcus pneumoniae (S. pneumoniae) (26.77%), Haemophilus influenza B (H. influenza B) (6.30%) and Enterobacteriaceae (1.57%). The results indicated that bacterial meningitis occur from November to May with a peak in February for H. influenzae and S. pneumoniae and March for Neisseriaceae. The distribution of positive CSF with regards to the age showed that subjects between 6 and 12 years followed by subjects of 0 to 5 years were most affected with respective frequencies of 67.82% and 56.52% (P<0.001). Susceptibility tests revealed that bacteria have developed resistance to several antibiotics including aminosides (resistance rate >20% for both bacterial strains), macrolides (resistance rate > 30% for H. influenzae) quinolones (resistance rate >15% for H. influenzae and N. meningitidis W135). Over three years, the prevalence of S. pneumoniae significantly increased from 8.48% to 73.33% (P<0.001), while the changes in the prevalence of H. influenzae B were not statistically significant: 4.24%, vs. 8.89%, (P = 0.233). Our results indicate that data in African countries differ depending on geographical location in relation to the African meningitis belt. This underlines the importance of epidemiological surveillance of bacterial meningitis. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Estimating costs associated with a community outbreak of meningococcal disease in a colombian Caribbean city.

PubMed

Pinzón-Redondo, Hernando; Coronell-Rodriguez, Wilfrido; Díaz-Martinez, Inés; Guzmán-Corena, Angel; Constenla, Dagna; Alvis-Guzmán, Nelson

2014-09-01

Meningococcal disease is a serious and potentially life-threatening infection that is caused by the bacterium Neisseria meningitidis (N. meningitidis), and it can cause meningitis, meningococcaemia outbreaks and epidemics. The disease is fatal in 9-12% of cases and with a death rate of up to 40% among patients with meningococcaemia. The objective of this study was to estimate the costs of a meningococcal outbreak that occurred in a Caribbean city of Colombia. We contacted experts involved in the outbreak and asked them specific questions about the diagnosis and treatment for meningococcal cases during the outbreak. Estimates of costs of the outbreak were also based on extensive review of medical records available during the outbreak. The costs associated with the outbreak were divided into the cost of the disease response phase and the cost of the disease surveillance phase. The costs associated with the outbreak control and surveillance were expressed in US$ (2011) as cost per 1,000 inhabitants. The average age of patients was 4.6 years (SD 3.5); 50% of the cases died; 50% of the cases were reported to have meningitis (3/6); 33% were diagnosed with meningococcaemia and myocarditis (2/6); 50% of the cases had bacteraemia (3/6); 66% of the cases had a culture specimen positive for Neisseria meningitidis; 5 of the 6 cases had RT-PCR positive for N. meningitidis. All N. meningitidis were serogroup B; 50 doses of ceftriaxone were administered as prophylaxis. Vaccine was not available at the time. The costs associated with control of the outbreak were estimated at US$ 0.8 per 1,000 inhabitants, disease surveillance at US$ 4.1 per 1,000 inhabitants, and healthcare costs at US$ 5.1 per 1,000 inhabitants. The costs associated with meningococcal outbreaks are substantial, and the outbreaks should be prevented. The mass chemoprophylaxis implemented helped control the outbreak.

Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival.

PubMed

Echenique-Rivera, Hebert; Muzzi, Alessandro; Del Tordello, Elena; Seib, Kate L; Francois, Patrice; Rappuoli, Rino; Pizza, Mariagrazia; Serruto, Davide

2011-05-01

During infection Neisseria meningitidis (Nm) encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating disease cause by this microorganism.

Transcriptome Analysis of Neisseria meningitidis in Human Whole Blood and Mutagenesis Studies Identify Virulence Factors Involved in Blood Survival

PubMed Central

Del Tordello, Elena; Seib, Kate L.; Francois, Patrice; Rappuoli, Rino; Pizza, Mariagrazia; Serruto, Davide

2011-01-01

During infection Neisseria meningitidis (Nm) encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating disease cause by this microorganism. PMID:21589640

[Meningococcal vulvovaginitis in a prepubertal girl].

PubMed

Nathanson, M; Tisseron, B; de Pontual, L

2005-12-01

Neisseria meningitidis is an uncommon cause of vulvovaginitis in the prepubertal girl. The microorganism must not be mistaken for Neisseria gonorrhoeae, as the consequences of such an error may be serious. Colonization or infection by Neisseria meningitis is not uncommon in adolescents and adults. Vulvitis, even when it is recurrent, is not per se a good indicator of sexual abuse, but some microorganisms found by vaginal swab can make it possible, likely or certain. Sexual transmission of N. meningitidis has not been described in the prepubertal child.

Neisseria meningitidis and Moraxella osloensis: dual infection in blood and peritoneal fluid.

PubMed

Tiosejo, L L; Hocko, M; Bartholomew, W R; Amsterdam, D

1988-12-01

The clinical course of a malnourished alcoholic in which Neisseria meningitidis was isolated from the blood and Moraxella osloensis from the peritoneal fluid is described. Following bacteriologic diagnosis, the patient was treated and responded to a course of penicillin therapy. To our knowledge, this represents the first case of peritonitis associated with M. osloensis. Clinical reports of the isolation of this organism are rare; its pathogenicity is not clearly established, and the presence of the organism may often be unrecognized.

Determination of the size and degree of acetyl substitution of oligosaccharides from Neisseria meningitidis group A by ionspray mass spectrometry.

PubMed

Cescutti, P; Bigio, M; Guarnieri, V

1996-07-16

The capsular polysaccharide produced by Neisseria meningitidis group A has the following structure: [formula: see text] [formula: see text] This polysaccharide was partially hydrolysed with acetic acid, and the oligomers obtained were separated by fast performance liquid chromatography. Six fractions were collected and characterised by ionspray mass spectrometry in the positive ion mode. This soft ionisation technique established the size of the obtained oligosaccharides and the degree of O-acetyl substitution for each fraction.

Meningococcal disease: recognition, treatment, and prevention.

PubMed

Herf, C; Nichols, J; Fruh, S; Holloway, B; Anderson, C U

1998-08-01

Meningococcal disease is an infection caused by Neisseria meningitidis, a gram-negative diplococcus that is the leading cause of bacterial meningitis in children and young adults in the United States, with an estimated 2,600 cases reported each year. N. meningitidis infection rates are highest in children 3 to 12 months of age. Four distinct clinical situations are associated with meningococcal infection. The most common is asymptomatic nasopharyngeal colonization. Benign bacteremia is discovered in the absence of classical clinical findings of meningococcemia, but blood cultures are positive for N. meningitidis. Meningitis, the most common pathologic presentation, is associated with fever, headache, and nuchal rigidity. The mortality rate is about 5% in children and 10% to 15% in adults. Meningococcemia, the most severe form of infection, may involve petechial rash, hypotension, and disseminated intravascular coagulation. It is a fulminant condition that can, if untreated, progress from initial symptoms to coma and death in 12 to 48 hours. Spread of these endemic cases can be controlled by administering prophylactic antibiotics to close contacts of patients.

A Versatile PDMS/Paper Hybrid Microfluidic Platform for Sensitive Infectious Disease Diagnosis

PubMed Central

2015-01-01

Bacterial meningitis is a serious health concern worldwide. Given that meningitis can be fatal and many meningitis cases occurred in high-poverty areas, a simple, low-cost, highly sensitive method is in great need for immediate and early diagnosis of meningitis. Herein, we report a versatile and cost-effective polydimethylsiloxane (PDMS)/paper hybrid microfluidic device integrated with loop-mediated isothermal amplification (LAMP) for the rapid, sensitive, and instrument-free detection of the main meningitis-causing bacteria, Neisseria meningitidis (N. meningitidis). The introduction of paper into the microfluidic device for LAMP reactions enables stable test results over a much longer period of time than a paper-free microfluidic system. This hybrid system also offers versatile functions, by providing not only on-site qualitative diagnostic analysis (i.e., a yes or no answer), but also confirmatory testing and quantitative analysis in laboratory settings. The limit of detection of N. meningitidis is about 3 copies per LAMP zone within 45 min, close to single-bacterium detection sensitivity. In addition, we have achieved simple pathogenic microorganism detection without a laborious sample preparation process and without the use of centrifuges. This low-cost hybrid microfluidic system provides a simple and highly sensitive approach for fast instrument-free diagnosis of N. meningitidis in resource-limited settings. This versatile PDMS/paper microfluidic platform has great potential for the point of care (POC) diagnosis of a wide range of infectious diseases, especially for developing nations. PMID:25019330

fbpABC gene cluster in Neisseria meningitidis is transcribed as an operon.

PubMed

Khun, H H; Deved, V; Wong, H; Lee, B C

2000-12-01

The neisserial fbpABC locus has been proposed to constitute a single transcriptional unit. To confirm this operonic arrangement, transcription assays using reverse transcriptase PCR amplification were conducted with Neisseria meningitidis. The presence of fbpAB and fbpBC transcripts obtained by priming cDNA synthesis with an fbpC-sequence-specific oligonucleotide indicates that fbpABC is organized as a single expression unit. The ratio of fbpA to fbpABC mRNA was approximately between 10- to 20-fold, as determined by real-time quantitative PCR.

fbpABC Gene Cluster in Neisseria meningitidis Is Transcribed as an Operon

PubMed Central

Khun, Heng H.; Deved, Vinay; Wong, Howard; Lee, B. Craig

2000-01-01

The neisserial fbpABC locus has been proposed to constitute a single transcriptional unit. To confirm this operonic arrangement, transcription assays using reverse transcriptase PCR amplification were conducted with Neisseria meningitidis. The presence of fbpAB and fbpBC transcripts obtained by priming cDNA synthesis with an fbpC-sequence-specific oligonucleotide indicates that fbpABC is organized as a single expression unit. The ratio of fbpA to fbpABC mRNA was approximately between 10- to 20-fold, as determined by real-time quantitative PCR. PMID:11083849

Functional Characterization of Lpt3 and Lpt6, the Inner-Core Lipooligosaccharide Phosphoethanolamine Transferases from Neisseria meningitidis▿

PubMed Central

Wenzel, Cory Q.; St. Michael, Frank; Stupak, Jacek; Li, Jianjun; Cox, Andrew D.; Richards, James C.

2010-01-01

The lipooligosaccharide (LOS) of Neisseria meningitidis contains heptose (Hep) residues that are modified with phosphoethanolamine (PEtn) at the 3 (3-PEtn) and/or 6 (6-PEtn) position. The lpt3 (NMB2010) and lpt6 (NMA0408) genes of N. meningitidis, which are proposed to encode the required HepII 3- and 6-PEtn transferases, respectively, were cloned and overexpressed as C-terminally polyhistidine-tagged fusion proteins in Escherichia coli and found to localize to the inner membrane, based on sucrose density gradient centrifugation. Lpt3-His6 and Lpt6-His6 were purified from Triton X-100-solubilized membranes by nickel chelation chromatography, and dot blot analysis of enzymatic reactions with 3-PEtn- and 6-PEtn-specific monoclonal antibodies demonstrated conclusively that Lpt3 and Lpt6 are phosphatidylethanolamine-dependent LOS HepII 3- and 6-PEtn transferases, respectively, and that both enzymes are capable of transferring PEtn to both fully acylated LOS and de-O-acylated (de-O-Ac) LOS. Further enzymatic studies using capillary electrophoresis-mass spectrometry (MS) demonstrated that both Lpt3 and Lpt6 are capable of transferring PEtn to de-O-Ac LOS molecules already containing PEtn at the 6 and 3 positions of HepII, respectively, demonstrating that there is no obligate order of PEtn addition in the generation of 3,6-di-PEtn LOS moieties in vitro. PMID:19854897

Towards understanding the epidemiology of Neisseria meningitidis in the African meningitis belt: a multi-disciplinary overview.

PubMed

Agier, Lydiane; Martiny, Nadège; Thiongane, Oumy; Mueller, Judith E; Paireau, Juliette; Watkins, Eleanor R; Irving, Tom J; Koutangni, Thibaut; Broutin, Hélène

2017-01-01

Neisseria meningitidis is the major cause of seasonal meningitis epidemics in the African meningitis belt. In the changing context of a reduction in incidence of serogroup A and an increase in incidence of serogroups W and C and of Streptococcus pneumoniae, a better understanding of the determinants driving the disease transmission dynamics remains crucial to improving bacterial meningitis control. The literature was searched to provide a multi-disciplinary overview of the determinants of meningitis transmission dynamics in the African meningitis belt. Seasonal hyperendemicity is likely predominantly caused by increased invasion rates, sporadic localized epidemics by increased transmission rates, and larger pluri-annual epidemic waves by changing population immunity. Carriage likely involves competition for colonization and cross-immunity. The duration of immunity likely depends on the acquisition type. Major risk factors include dust and low humidity, and presumably human contact rates and co-infections; social studies highlighted environmental and dietary factors, with supernatural explanations. Efforts should focus on implementing multi-country, longitudinal seroprevalence and epidemiological studies, validating immune markers of protection, and improving surveillance, including more systematic molecular characterizations of the bacteria. Integrating climate and social factors into disease control strategies represents a high priority for optimizing the public health response and anticipating the geographic evolution of the African meningitis belt. Copyright © 2016. Published by Elsevier Ltd.

Discovery of a novel protein modification: alpha-glycerophosphate is a substituent of meningococcal pilin.

PubMed Central

Stimson, E; Virji, M; Barker, S; Panico, M; Blench, I; Saunders, J; Payne, G; Moxon, E R; Dell, A; Morris, H R

1996-01-01

Pili, which are filamentous protein structures on the surface of the meningitis-causing organism Neisseria meningitidis, are known to be post-translationally modified with substituents that affect their mobility in SDS/PAGE and which might play a crucial role in adherence and bloodstream invasion. Tryptic digests of pili were analysed by fast atom bombardment and electrospray MS to identify putative modifications. Serine-93 was found to carry a novel modification of alpha-glycerophosphate. This is the first time that alpha-glycerophosphate has been observed as a substituent of a prokaryotic or eukaryotic protein. PMID:8645220

Bacterial meningitis epidemiology and return of Neisseria meningitidis serogroup A cases in Burkina Faso in the five years following MenAfriVac mass vaccination campaign.

PubMed

Diallo, Alpha Oumar; Soeters, Heidi M; Yameogo, Issaka; Sawadogo, Guetawendé; Aké, Flavien; Lingani, Clément; Wang, Xin; Bita, Andre; Fall, Amadou; Sangaré, Lassana; Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Bicaba, Brice; Novak, Ryan T

2017-01-01

Historically, Neisseria meningitidis serogroup A (NmA) caused large meningitis epidemics in sub-Saharan Africa. In 2010, Burkina Faso became the first country to implement a national meningococcal serogroup A conjugate vaccine (MACV) campaign. We analyzed nationwide meningitis surveillance data from Burkina Faso for the 5 years following MACV introduction. We examined Burkina Faso's aggregate reporting and national laboratory-confirmed case-based meningitis surveillance data from 2011-2015. We calculated incidence (cases per 100,000 persons), and described reported NmA cases. In 2011-2015, Burkina Faso reported 20,389 cases of suspected meningitis. A quarter (4,503) of suspected meningitis cases with cerebrospinal fluid specimens were laboratory-confirmed as either S. pneumoniae (57%), N. meningitidis (40%), or H. influenzae (2%). Average adjusted annual national incidence of meningococcal meningitis was 3.8 (range: 2.0-10.2 annually) and was highest among infants aged <1 year (8.4). N. meningitidis serogroup W caused the majority (64%) of meningococcal meningitis among all age groups. Only six confirmed NmA cases were reported in 2011-2015. Five cases were in children who were too young (n = 2) or otherwise not vaccinated (n = 3) during the 2010 MACV mass vaccination campaign; one case had documented MACV receipt, representing the first documented MACV failure. Meningococcal meningitis incidence in Burkina Faso remains relatively low following MACV introduction. However, a substantial burden remains and NmA transmission has persisted. MACV integration into routine childhood immunization programs is essential to ensure continued protection.

Prevalence of meningococcal carriage in children and adolescents aged 10-19 years in Chile in 2013.

PubMed

Díaz, Janepsy; Cárcamo, Marcela; Seoane, Mabel; Pidal, Paola; Cavada, Gabriel; Puentes, Rodrigo; Terrazas, Solana; Araya, Pamela; Ibarz-Pavon, Ana B; Manríquez, Macarena; Hormazábal, Juan C; Ayala, Salvador; Valenzuela, María T

2016-01-01

In 2011, Chile experienced an increase in the number of cases of IMD caused by Neisseria meningitidis group W. This epidemiological scenario prompted authorities to implement prevention strategies. As part of these strategies, the Institute of Public Heath of Chile conducted a cross-sectional study to determine the prevalence of pharyngeal carriage of N. meningitidis in a representative sample of healthy children and adolescents aged 10-19 years. The identification of presumptive N. meningitidis strains was performed by testing carbohydrate utilization in the National Reference Laboratory at the ISP. Association of meningococcal carriage with risk factors was analyzed by calculating the Odds Ratio. Selected variables were included in a logistic model for risk analyses. The prevalence of carriage of N. meningitidis was 6.5% (CI: 5.7-7.3%). Older age (carriers: 14.2±0.29 vs. non-carriers: 13.8±0.08 years old; p=0.009), cohabitation with children (carriers: 0.9±0.13 vs. non-carriers: 0.7±0.03; p=0.028), number of smoking cohabitants (carriers: 0.55±0.13 vs. non-carriers: 0.44±0.03) and frequent attendance to crowded social venues (carriers: 49% vs. non-carriers: 37%; p=0.008) were determined to favor carriage. Statistical modeling showed that meningococcal carriage was associated with older age (OR: 1.077, p-value: 0.002) and cohabitation with children (OR: 1.182, p-value: 0.02). Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers.

PubMed

Bryant, Kristina A; Marshall, Gary S

2011-07-01

The highest rates of invasive meningococcal disease occur in children under 2 years of age, yet as of early 2011 no vaccine was licensed for the youngest infants. However, a novel vaccine consisting of capsular polysaccharides from Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y conjugated to tetanus toxoid (HibMenCY-TT; MenHibrix, GlaxoSmithKline) is in the late stages of development. In clinical trials involving more than 7800 children, HibMenCY-TT was shown to be safe and immunogenic when administered at 2, 4, 6 and 12-15 months of age. Anti-polyribosylribitol phosphate antibody responses were noninferior to those elicited by licensed monovalent Hib vaccines, and most vaccinees developed bactericidal antibodies against N. meningitidis serogroups C and Y. The majority of subjects retained antibody responses as far as 3 years after vaccination. If licensed, HibMenCY-TT not only represents an incremental option for protection against invasive Hib, but also has the potential to prevent invasive meningococcal disease without increasing the number of injections.

[In silico identification of molecular mimicry between T-cell epitopes of Neisseria meningitidis B and the human proteome].

PubMed

Batista-Duharte, Alexander; Téllez, Bruno; Tamayo, Maybia; Portuondo, Deivys; Cabrera, Osmir; Sierra, Gustavo; Pérez, Oliver

2013-07-01

The objective of the study was to determine the T-cell epitopes of four of the most frequent antigenic proteins of the outer membrane of Neisseria meningitidis B, and to identify the most relevant sites for molecular mimicry with T-cell epitopes in humans. In order to do so, an in silico study -a type of study that uses bioinformatic tools- was carried out using SWISS-PROT/TrEMBL, SYFPEITHI and FASTA databases, which helped to determine the protein sequences, CD4 and CD8 T-cell epitope prediction, as well as the molecular mimicry with humans, respectively. Molecular similarity was found in several human proteins present in different organs and tissues such as: liver, skin and epithelial tissues, brain, lymphatic system and testicles. Of these, those found in testicles were more similar, showing the highest frequency of mimetic sequences. This finding shed light on the success of N. meningitidis B to colonize human tissues and the failure of certain vaccines against this bacterium, and it even helps to explain possible autoimmune reactions associated with the infection or vaccination.

Visualisation and quantification of intracellular interactions of Neisseria meningitidis and human α-actinin by confocal imaging.

PubMed

Murillo, Isabel; Virji, Mumtaz

2010-10-24

The Opc protein of Neisseria meningitidis (Nm, meningococcus) is a surface-expressed integral outer membrane protein, which can act as an adhesin and an effective invasin for human epithelial and endothelial cells. We have identified endothelial surface-located integrins as major receptors for Opc, a process which requires Opc to first bind to integrin ligands such as vitronectin and via these to the cell-expressed receptors(1). This process leads to bacterial invasion of endothelial cells(2). More recently, we observed an interaction of Opc with a 100 kDa protein found in whole cell lysates of human cells(3). We initially observed this interaction when host cell proteins separated by electrophoresis and blotted on to nitrocellulose were overlaid with Opc-expressing Nm. The interaction was direct and did not involve intermediate molecules. By mass spectrometry, we established the identity of the protein as α-actinin. As no surface expressed α-actinin was found on any of the eight cell lines examined, and as Opc interactions with endothelial cells in the presence of serum lead to bacterial entry into the target cells, we examined the possibility of the two proteins interacting intracellularly. For this, cultured human brain microvascular endothelial cells (HBMECs) were infected with Opc-expressing Nm for extended periods and the locations of internalised bacteria and α-actinin were examined by confocal microscopy. We observed time-dependent increase in colocalisation of Nm with the cytoskeletal protein, which was considerable after an eight hour period of bacterial internalisation. In addition, the use of quantitative imaging software enabled us to obtain a relative measure of the colocalisation of Nm with α-actinin and other cytoskeletal proteins. Here we present a protocol for visualisation and quantification of the colocalisation of the bacterium with intracellular proteins after bacterial entry into human endothelial cells, although the procedure is also applicable to human epithelial cells.

Mu-Like Prophage in Serogroup B Neisseria meningitidis Coding for Surface-Exposed Antigens

PubMed Central

Masignani, Vega; Giuliani, Marzia Monica; Tettelin, Hervé; Comanducci, Maurizio; Rappuoli, Rino; Scarlato, Vincenzo

2001-01-01

Sequence analysis of the genome of Neisseria meningititdis serogroup B revealed the presence of an ∼35-kb region inserted within a putative gene coding for an ABC-type transporter. The region contains 46 open reading frames, 29 of which are colinear and homologous to the genes of Escherichia coli Mu phage. Two prophages with similar organizations were also found in serogroup A meningococcus, and one was found in Haemophilus influenzae. Early and late phage functions are well preserved in this family of Mu-like prophages. Several regions of atypical nucleotide content were identified. These likely represent genes acquired by horizontal transfer. Three of the acquired genes are shown to code for surface-associated antigens, and the encoded proteins are able to induce bactericidal antibodies. PMID:11254622

Comparison and Correlation of Neisseria meningitidis Serogroup B Immunologic Assay Results and Human Antibody Responses following Three Doses of the Norwegian Meningococcal Outer Membrane Vesicle Vaccine MenBvac

PubMed Central

Findlow, Jamie; Taylor, Stephen; Aase, Audun; Horton, Rachel; Heyderman, Robert; Southern, Jo; Andrews, Nick; Barchha, Rita; Harrison, Ewan; Lowe, Ann; Boxer, Emma; Heaton, Charlotte; Balmer, Paul; Kaczmarski, Ed; Oster, Philipp; Gorringe, Andrew; Borrow, Ray; Miller, Elizabeth

2006-01-01

The prediction of efficacy of Neisseria meningitidis serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease. PMID:16861642

Meningococcal pneumonia in Japan: A case report and literature review.

PubMed

Hirai, Jun; Kinjo, Takeshi; Tome, Takaaki; Hagihara, Mao; Sakanashi, Daisuke; Nakamura, Hideta; Haranaga, Shusaku; Mikamo, Hiroshige; Fujita, Jiro

2016-12-01

Neisseria meningitidis often causes meningitis and meningococcemia; however, meningococcal pneumonia is quite rare. Herein, we report a case of non-invasive meningococcal pneumonia initially misdiagnosed as pneumonia due to Moraxella catarrhalis on the basis of a Gram stain in a 43-year-old woman with asthma, type 2 diabetes mellitus, and schizophrenia. She visited our hospital following a 3-day history of fever, productive cough, and shortness of breath. Since her sputum smear revealed Gram-negative diplococcus and the chest radiograph showed infiltration in the lower right lung field, her initial diagnosis was pneumonia caused by M. catarrhalis. However, the next day, the sputum culture colonies were unlike those of M. catarrhalis, and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis revealed the pathogen to be N. meningitidis. As a result, we administered the appropriate treatment and ensured adequate infection prevention and control measures including, droplet precautions and prophylaxis provided to close contacts. Secondary infection did not occur. Although meningococcal pneumonia is not common, physicians should consider N. meningitidis when Gram-negative diplococci are observed in respiratory specimens, as N. meningitidis cannot be distinguished from M. catarrhalis with Gram staining alone. Moreover, it is also important to monitor the appearance of the pathogenic colonies and to closely coordinate with laboratory technicians to determine appropriate treatments. In this article, we review the previous case reports of meningococcal pneumonia reported in 1984-2015 in Japan, summarizing the clinical characteristics and comparing previous reviews of the literature. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Use of Heme Compounds as Iron Sources by Pathogenic Neisseriae Requires the Product of the hemO Gene

PubMed Central

Zhu, Wenming; Hunt, Desiree J.; Richardson, Anthony R.; Stojiljkovic, Igor

2000-01-01

Heme compounds are an important source of iron for neisseriae. We have identified a neisserial gene, hemO, that is essential for heme, hemoglobin (Hb), and haptoglobin-Hb utilization. The hemO gene is located 178 bp upstream of the hmbR Hb receptor gene in Neisseria meningitidis isolates. The product of the hemO gene is homologous to enzymes that degrade heme; 21% of its amino acid residues are identical, and 44% are similar, to those of the human heme oxygenase-1. DNA sequences homologous to hemO were ubiquitous in commensal and pathogenic neisseriae. HemO genetic knockout strains of Neisseria gonorrhoeae and N. meningitidis were unable to use any heme source, while the assimilation of transferrin-iron and iron-citrate complexes was unaffected. A phenotypic characterization of a conditional hemO mutant, constructed by inserting an isopropyl-β-d-thiogalactopyranoside (IPTG)-regulated promoter upstream of the ribosomal binding site of hemO, confirmed the indispensability of the HemO protein in heme utilization. The expression of HemO also protected N. meningitidis cells against heme toxicity. hemO mutants were still able to transport heme into the cell, since both heme and Hb could complement an N. meningitidis hemA hemO double mutant for growth. The expression of the HmbR receptor was reduced significantly by the inactivation of the hemO gene, suggesting that hemO and hmbR are transcriptionally linked. The expression of the unlinked Hb receptor, HpuAB, was not altered. Comparison of the polypeptide patterns of the wild type and the hemO mutant led to detection of six protein spots with an altered expression pattern, suggesting a more general role of HemO in the regulation of gene expression in Neisseriae. PMID:10629191

Focusing homologous recombination: pilin antigenic variation in the pathogenic Neisseria

PubMed Central

Cahoon, Laty A.; Seifert, H. Steven

2011-01-01

Summary Some pathogenic microbes utilize homologous recombination to generate antigenic variability in targets of immune surveillance. These specialized systems rely on the cellular recombination machinery to catalyze dedicated, high-frequency reactions that provide extensive diversity in the genes encoding surface antigens. A description of the specific mechanisms that allow unusually high rates of recombination without deleterious effects on the genome in the well characterized pilin antigenic variation systems of Neisseria gonorrhoeae and Neisseria meningitidis is presented. We will also draw parallels to selected bacterial and eukaryotic antigenic variation systems, and suggest the most pressing unanswered questions related to understanding these important processes. PMID:21812841

Vaccination in Southeast Asia--reducing meningitis, sepsis and pneumonia with new and existing vaccines.

PubMed

Richardson, Alice; Morris, Denise E; Clarke, Stuart C

2014-07-16

Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are leading causes of vaccine-preventable diseases such as meningitis, sepsis and pneumonia. Although there has been much progress in the introduction of vaccines against these pathogens, access to vaccines remains elusive in some countries. This review highlights the current S. pneumoniae, H. influenzae type b, and N. meningitidis immunization schedules in the 10 countries belonging to the Association of Southeast Asian Nations (ASEAN). Epidemiologic studies may be useful for informing vaccine policy in these countries, particularly when determining the cost-effectiveness of introducing new vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neisseria meningitidis: a neglected cause of infectious haemorrhagic fever in the amazon rainforest.

PubMed

Barroso, David E; Silva, Luciete A

2007-12-01

Neisseria meningitidis has not been seen as a significant cause of infectious haemorrhagic fever in the Amazon inlands; most reported cases are from the city of Manaus, the capital of the State of Amazonas. This picture is sustained by the lack of reliable microbiology laboratories, the perception of the health care workers, and the difficult to reach medical assistance; thus the number of confirmed cases is even lower with no reference of the strains phenotype. We report here the investigation of a case of suspected meningococcemia and his close contacts in a rural community in the Coari Lake, up the Amazon River.

A Neisseria meningitidis fbpABC mutant is incapable of using nonheme iron for growth.

PubMed

Khun, H H; Kirby, S D; Lee, B C

1998-05-01

The neisserial fbpABC locus has been proposed to act as an iron-specific ABC transporter system. To confirm this assigned function, we constructed an fbpABC mutant in Neisseria meningitidis by insertional inactivation of fbpABC with a selectable antibiotic marker. The mutant was unable to use iron supplied from human transferrin, human lactoferrin, or iron chelates. However, the use of iron from heme and human hemoglobin was unimpaired. These results support the obligatory participation of fbpABC in neisserial periplasmic iron transport and do not indicate a role for this genetic locus in the heme iron pathway.

A Neisseria meningitidis fbpABC Mutant Is Incapable of Using Nonheme Iron for Growth

PubMed Central

Khun, Heng H.; Kirby, Shane D.; Lee, B. Craig

1998-01-01

The neisserial fbpABC locus has been proposed to act as an iron-specific ABC transporter system. To confirm this assigned function, we constructed an fbpABC mutant in Neisseria meningitidis by insertional inactivation of fbpABC with a selectable antibiotic marker. The mutant was unable to use iron supplied from human transferrin, human lactoferrin, or iron chelates. However, the use of iron from heme and human hemoglobin was unimpaired. These results support the obligatory participation of fbpABC in neisserial periplasmic iron transport and do not indicate a role for this genetic locus in the heme iron pathway. PMID:9573125

[Surveillance of Neisseria meningitidis in Argentina, 1993-2005: distribution of serogroups, serotypes and serosubtypes isolated from invasive disease].

PubMed

Chiávetta, L; Chávez, E; Ruzic, A; Mollerach, M; Regueira, M

2007-01-01

Neisseria meningitidis is an important cause of meningitis, bacteremia and septic shock syndrome. We herein present the distribution of serogroups, serotypes and serosubtypes of 2244 isolates of N. meningitidis from patients with meningitis or meningococcemia, received within the period 1993-2005, in the National Reference Laboratory, INEI-ANLIS "Dr. Carlos G. Malbrán", from 33 Argentine hospitals that are included in a National Network devoted to for the study of bacterial meningitis. Between 1993-1995, serogroup B was prevalent (66%) whereas in the period from 1995-2001, serogroup C prevailed (65%). However, following but after that period, the prevalence of serogroup B was recovered. In the last 5 years of the studied period, the serogroups Y and W135 represented as a whole a 15.6% as a whole whereas up to the year 2000 during the first 6 years they accounted for it was of 4.7%. Higher diversity in the distribution of serotypes and serosubtypes was observed within serogroup B. The nonsubtypable isolates throughout the period of study represented the 52.8%, this high percentage demonstrates the limited capacity of the serotyping for the determination of meningococcal/meningococcus subtypes. of meningococco.

Mechanisms of Dexamethasone-Mediated Inhibition of Toll-Like Receptor Signaling Induced by Neisseria meningitidis and Streptococcus pneumoniae▿

PubMed Central

Mogensen, Trine H.; Berg, Randi S.; Paludan, Søren R.; Østergaard, Lars

2008-01-01

Excessive inflammation contributes to the pathogenesis of bacterial meningitis, which remains a serious disease despite treatment with antibiotics. Therefore, anti-inflammatory drugs have important therapeutic potential, and clinical trials have revealed that early treatment with dexamethasone significantly reduces mortality and morbidity from bacterial meningitis. Here we investigate the molecular mechanisms behind the inhibitory effect of dexamethasone upon the inflammatory responses evoked by Neisseria meningitidis and Streptococcus pneumoniae, two of the major causes of bacterial meningitis. The inflammatory cytokine response was dependent on Toll-like receptor signaling and was strongly inhibited by dexamethasone. Activation of the NF-κB pathway was targeted at several levels, including inhibition of IκB phosphorylation and NF-κB DNA-binding activity as well as upregulation of IκBα synthesis. Our data also revealed that the timing of steroid treatment relative to infection was important for achieving strong inhibition, particularly in response to S. pneumoniae. Altogether, we describe important targets of dexamethasone in the inflammatory responses evoked by N. meningitidis and S. pneumoniae, which may contribute to our understanding of the clinical effect and the importance of timing with respect to corticosteroid treatment during bacterial meningitis. PMID:17938219

A network of enzymes involved in repair of oxidative DNA damage in Neisseria meningitidis

PubMed Central

Li, Yanwen; Pelicic, Vladimir; Freemont, Paul S.; Baldwin, Geoff S.; Tang, Christoph M.

2013-01-01

Although oxidative stress is a key aspect of innate immunity, little is known about how host-restricted pathogens successfully repair DNA damage. Base excision repair (BER) is responsible for correcting nucleobases damaged by oxidative stress, and is essential for bloodstream infection caused by the human pathogen, Neisseria meningitidis. We have characterised meningococcal BER enzymes involved in the recognition and removal of damaged nucleobases, and incision of the DNA backbone. We demonstrate that the bi-functional glycosylase/lyases Nth and MutM share several overlapping activities and functional redundancy. However MutM and other members of the GO system, which deal with 8-oxoG, a common lesion of oxidative damage, are not required for survival of N. meningitidis under oxidative stress. Instead, the mismatch repair pathway provides back-up for the GO system, while the lyase activity of Nth can substitute for the meningococcal AP endonuclease, NApe. Our genetic and biochemical evidence show that DNA repair is achieved through a robust network of enzymes that provides a flexible system of DNA repair. This network is likely to reflect successful adaptation to the human nasopharynx, and might provide a paradigm for DNA repair in other prokaryotes. PMID:22296581

Genetic relationships and clonal population structure of serotype 2 strains of Neisseria meningitidis.

PubMed Central

Caugant, D A; Zollinger, W D; Mocca, L F; Frasch, C E; Whittam, T S; Frøholm, L O; Selander, R K

1987-01-01

Two hundred and thirty-four strains of Neisseria meningitidis, including 94 serotype 2a, 111 serotype 2b, and 19 serotype 2c isolates, together with 10 isolates that were serotyped as 2 with polyvalent antiserum but did not react with monoclonal antibodies, were characterized by the electrophoretic mobilities of 15 metabolic enzymes. Of these enzymes, 14 were polymorphic, and 56 distinctive combinations of alleles at the enzyme loci (electrophoretic types) were identified, among which the mean genetic diversity per locus was 0.413, or about 75% of that recorded for the species N. meningitidis as a whole. Mean genetic diversity among electrophoretic types of the same serotype (2a, 2b, or 2c) was, however, on average, less than half the total species diversity, and no multilocus genotypes were shared between isolates of the different serotypes, which belong to distinctive clonal lineages. Recent temporal changes in the frequencies of recovery of pathogenic strains of serotypes 2a and 2b in South Africa and North America resulted from clone replacement in these populations rather than evolutionary modification of the serotype protein of the initially dominant clones. PMID:3106223

Paediatric meningococcaemia in northwestern Ontario, Canada: a case for publicly funded meningococcal B vaccination

PubMed Central

Tsang, Raymond S. W.; Ulanova, Marina

2016-01-01

Introduction: Neisseria meningitidis serogroup B is an important infectious agent in developed countries, including Canada. Infants are particularly susceptible to infection with serogroup B because of immature immune systems, pathogen virulence factors and changing serogroup dynamics in the post-vaccination era. Currently, the Ontario provincial government does not include serogroup B in its routine publicly funded meningococcal vaccination program. Case Presentation: A formerly well 14-month-old male presented to a tertiary hospital emergency department with fever, minor respiratory problems, diffuse purpuric rash, distended abdomen, tachycardia, and history of one episode of vomiting and melena each. Meningococcaemia was immediately suspected, and he was treated with ceftriaxone, cefotaxime and vancomycin before transfer to a different acute care facility within 12 h. N. meningitidis serogroup B, sensitive to ceftriaxone and penicillin, was identified in his blood. The patient developed gangrene of the lower legs and underwent bilateral below-knee amputation 8 days post-admission. Conclusion: This instance of meningococcaemia with extensive sequelae is an example of the various serious outcomes of meningococcal infection. It provides persuasive reason for routine publicly funded vaccination against N. meningitidis serogroup B in Ontario. PMID:28348748

Comparison of a rapid micromedia method to cystine trypticase agar (CTA) and fluorescent methods for the identification of pathogenic Neisseria.

PubMed

Brake, S R; Marsik, F J; Rein, M R

1982-01-01

A four-hour micromedia method which detects enzymes formed by bacteria for the degradion of carbohydrates was compared to the utilization of carbohydrates was compared to the utilization of carbohydrates in cystine tyrpticase agar (CTA) for the identification of Neisseria gonorrhoeae and Neisseria meningitidis. This rapid micromedia method (RMM) correlated 100% with the utilization of carbohydrates in CTA. Identification of N. gonorrhoeae by RMM was compared to the identification achieved by a commercially available coagglutination method and a fluorescent antibody (FA) technique. Of 144 isolates identified as N. gonorrhoeae by RMM, 122 (84.7%) were identified by coagglutination and 141 (97.9%) were identified by FA as N. gonorrhoeae. Five (13%) of 40 isolates identified as N. meningitidis by RMM were identified as N. gonorrhoeae by coagglutination while eleven (28%) were identified as N. gonorrhoeae by the FA technique. One (14%) and four (57%) of seven isolates identified as Neisseria species were identified as N. gonorrhoeae by coagglutination and the FA technique respectively. The rapid micromedia method was found to be a quick, sensitive, specific and economic way of identifying N. gonorrhoeae and N. meningitidis.

Characterization of epidemic Neisseria meningitidis serogroup C strains in several Brazilian states.

PubMed Central

Sacchi, C T; Tondella, M L; de Lemos, A P; Gorla, M C; Berto, D B; Kumiochi, N H; Melles, C E

1994-01-01

Epidemic strains of the Neisseria meningitidis C:2b:P1.3 electrophoretic type 11 complex were responsible for an outbreak in Curitiba, Parana State, Brazil, from 1990 to 1991. Strains of this complex were also isolated in other Brazilian states and were responsible for a meningococcal disease epidemic in São Paulo State in 1990. Serotyping both with monoclonal antibodies and by multilocus enzyme electrophoresis was useful for typing these epidemic strains related to the increased incidence of meningococcal disease. The genetic similarity of members of the electrophoretic type 11 complex was confirmed by the ribotyping method by using EcoRI or ClaI endonuclease restriction enzymes. Images PMID:7929775

Epidemiological evidence for the role of the haemoglobin receptor, HmbR, in meningococcal virulence

PubMed Central

Harrison, Odile B.; Evans, Nicholas J.; Blair, Jessica M.; Grimes, Holly S.; Tinsley, Colin R.; Nassif, Xavier; Kriz, Paula; Ure, Roisin; Gray, Steve J.; Derrick, Jeremy P.; Maiden, Martin C.J.; Feavers, Ian M.

2009-01-01

The distribution of the haemoglobin receptor gene (hmbR) was investigated in disease and carried Neisseria meningitidis isolates revealing that the gene occurred at a significantly higher frequency in disease isolates compared to those obtained from carriage. Where hmbR was absent, the locus was occupied by the cassettes exl2 or exl3, or with a “pseudo hmbR” gene designated exl4. The hmbR locus in published N. meningitidis genomes, as well as N. gonorrhoeae and N. lactamica ST-640, exhibited characteristics of a pathogenicity island. These data are consistent with a role for the hmbR gene in meningococcal disease. PMID:19476432

Nasopharyngeal culture

MedlinePlus

Culture - nasopharyngeal; Swab for respiratory viruses; Swab for staph carriage ... test identifies viruses and bacteria that cause upper respiratory tract symptoms. These include: Bordetella pertussis Neisseria meningitidis ...

Epidemiology of bacterial meningitis in the North American Arctic, 2000-2010.

PubMed

Gounder, Prabhu P; Zulz, Tammy; Desai, Shalini; Stenz, Flemming; Rudolph, Karen; Tsang, Raymond; Tyrrell, Gregory J; Bruce, Michael G

2015-08-01

To determine the incidence of meningitis caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in the North American Arctic during 2000-2010. Surveillance data were obtained from the International Circumpolar Surveillance network. We defined a case of bacterial meningitis caused by H. influenzae, N. meningitidis, or S. pneumoniae as a culture-positive isolate obtained from a normally sterile site in a resident with a meningitis diagnosis. The annual incidence/100,000 persons for meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae among all North American Arctic residents was: 0.6, 0.5, and 1.5, respectively; the meningitis incidence among indigenous persons in Alaska and Canada (indigenous status not recorded in Greenland) for those three bacteria was: 2.1, 0.8, and 2.4, respectively. The percentage of pneumococcal isolates belonging to a 7-valent pneumococcal conjugate vaccine serotype declined from 2000-2004 to 2005-2010 (31%-2%, p-value <0.01). During 2005-2010, serotype a caused 55% of H. influenzae meningitis and serogroup B caused 86% of meningococcal meningitis. Compared with all North American Arctic residents, indigenous people suffer disproportionately from bacterial meningitis. Arctic residents could benefit from the development of an H. influenzae serotype a vaccine and implementation of a meningococcal serogroup B vaccine. Published by Elsevier Ltd.

Outer Membrane Vesicles from Neisseria Meningitidis (Proteossome) Used for Nanostructured Zika Virus Vaccine Production.

PubMed

Martins, Paula; Machado, Daisy; Theizen, Thais Holtz; Guarnieri, João Paulo Oliveira; Bernardes, Bruno Gaia; Gomide, Gabriel Piccirillo; Corat, Marcus Alexandre Finzi; Abbehausen, Camilla; Módena, José Luiz Proença; Melo, Carlos Fernando Odir Rodrigues; Morishita, Karen Noda; Catharino, Rodrigo Ramos; Arns, Clarice Weis; Lancellotti, Marcelo

2018-05-29

The increase of Zika virus (ZIKV) infections in Brazil in the last two years leaves a prophylactic measures on alert for this new and emerging pathogen. Concerning of our positive experience, we developed a new prototype using Neisseria meningitidis outer membrane vesicles (OMV) on ZIKV cell growth in a fusion of OMV in the envelope of virus particles. The fusion of nanoparticles resulting from outer membrane vesicles of N. meningitidis with infected C6/36 cells line were analyzed by Nano tracking analysis (NTA), zeta potential, differential light scattering (DLS), scan and scanning transmission eletronic microscopy (SEM and STEM) and high resolution mass spectometry (HRMS) for nanostructure characterization. Also, the vaccination effects were viewed by immune response in mice protocols immunization (ELISA and inflammatory chemokines) confirmed by Zika virus soroneutralization test. The results of immunizations in mice showed that antibody production had a titer greater than 1:160 as compared to unvaccinated mice. The immune response of the adjuvant and non-adjuvant formulation activated the cellular immune response TH1 and TH2. In addition, the serum neutralization was able to prevent infection of virus particles in the glial tumor cell model (M059J). This research shows efficient strategies without recombinant technology or DNA vaccines.

New proteoliposome vaccine formulation from N. meningitidis serogroup B, without aluminum hydroxide, retains its antimeningococcal protectogenic potential as well as Th-1 adjuvant capacity

PubMed Central

2013-01-01

Proteoliposomes purified from the Outer Membrane of Neisseria meningitidis B, have been successfully used as core for adjuvants and vaccine formulations. We have tried to increase their structural definition and to conserve their efficacy and stability avoiding the addition of the aluminum hydroxide to the final formulation. Liposomal particle systems were prepared from components of defined molecular structure, such as a Neisseria meningitidis B protein complex, extracted and purified without forming vesicle structures. Liposomes were prepared from a mixture of dioleoyl phosphatidyl serine and cholesterol, using the classical dehydration-rehydration method. Transmission Electron Microscopy (TEM) was used to characterize the liposomes. BALB/c mice were used for animal testing procedures. Analysis of specific IgG response, serum bactericidal activity as well as DTH reaction was carried out. Isolation and purification of mRNA and real-time PCR, was performed to determine the dominating Th lymphokine pattern. The new antimeningococcal formulation without aluminum hydroxide prepared with components of defined molecular structure assembled itself into Neoproteoliposomes (NPL) ranging from 50 to 70 nm in diameter. The extraction and purification of selected membrane proteins to provide the antigen for this new formulation (PD-Tp), as well as the NPL-formulation favors a Th1 response pattern, suggested by the higher percentages of DTH, increased expression of proinflamatory lymphokine mRNAs when administered by intramuscular and intranasal routes. It stimulates a systemic bactericidal antibody response against Neisseria meningitidis B and immunologic memory similar to the Cuban VA-MENGOC-BC® vaccine, even at lower dosages and is less reactogenic at the injection site in comparison with the formulation with aluminum hydroxide. This new adjuvant formulation could be applicable to the development of new and improved vaccines against meningococcal disease, and eventually as modulators of the immune response against other diseases. PMID:23458443

Evaluation of Pastorex meningitis kit performance for the rapid identification of Neisseria meningitidis serogroup C in Nigeria

PubMed Central

Uadiale, Kennedy; Bestman, Agatha; Kamau, Charity; Caugant, Dominique A.; Greig, Jane

2016-01-01

Background Neisseria meningitidis serogroup C (NmC) has caused outbreaks in Nigeria of increasing size in three consecutive years since 2013. Rapid diagnostic tests (RDTs) for meningitis can facilitate quick identification of the causative pathogen; Pastorex can detect N. meningitidis serogroups A, C (NmC), Y/W135, N. meningitidis serogroup B/Escherichia coli K1, Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and group B Streptococcus. There is no published field evaluation of Pastorex in the identification of NmC. We report our experience with Pastorex in detecting NmC in field conditions. Methods During sequential outbreaks of NmC in Nigeria in 2013, 2014 and 2015, cerebrospinal fluid (CSF) was collected from suspected cases of meningitis that met the case definition. Pastorex latex agglutination rapid test was done in the field and trans-isolate media were inoculated with CSF for culture and/or PCR, which was used as the reference standard for 63 paired samples. Results The sensitivity of Pastorex for NmC was 80.0% (95% CI 65.4–90.4%) and the specificity was 94.4% (95% CI 72.7–99.9%). The positive likelihood ratio (LR) was 14.4 (95% CI 2.1–97.3) and negative LR was 0.2 (95% CI 0.1–0.4). The positive and negative predictive values (PPV and NPV) were 97.3% (95% CI 85.8–99.9) and 65.4% (95% CI 44.3–82.8), respectively, with a prevalence estimate of 71.4% (95% CI 58.6–82.1). Conclusion Pastorex showed good performance in detecting NmC under field conditions. Prepositioning Pastorex at peripheral health facilities during non-epidemic periods is constrained by a short shelf-life of 1 month after the kit is opened. There is need for development of RDTs that are cheaper and with less challenging requirements for storage and usage. PMID:27496511

The hyperferremic mouse model for the evaluation of the effectiveness of VA-MENGOC-BC against Neisseria meningitidis B clinical isolates.

PubMed

Sifontes, S; Infante, J F; Pérez, P; Caro, E; Sierra, G; Campa, C

1997-01-01

VA-MENGOC-BC is a vaccine against B and C serogroups of Neisseria meningitidis. Its effectiveness at population level has been shown after the application of the vaccine in Cuba, Brazil, Argentina and Colombia. In vitro assays are not always able to reproduce the microorganism-host relationships and this makes it necessary to compile and standardize results obtained in animal models to extrapolate them with a greater degree of safety for humans. We evaluated the effectiveness of VA-MENGOC-BC against Neisseria meningitidis group B isolates from clinically ill patients in Latin America (Argentina, B not typeable: P1; Chile, not typed; Colombia, B4:P1.15 and Cuba B4:P1.15) using Balb/cJ mice treated with iron to make them susceptible to Neisseria meningitidis. The lethal median dose of each strain and of two others that were not included in challenge assays (Brazil: P1.15 and Argentina, B2b:P1.10) were determined. Results were 2.68 x 10(6), 3.16 x 10(7), 1.98 x 10(8), 1.28 x 10(9), 6.42 x 10(6) and 3.88 x 10(7) colony forming units (CFU), respectively. Non-immunized animals and mice treated with one and two doses of VA-MENGOC-BC were challenged with 10(3)-(10) CFU. Protection ranged from 30 to 100% with one dose and was equal to or higher than 70% with the two-dose immunization schedule. A significant protection could not be observed against the Colombian isolate from the lethality point of view, but the mean time of survival lengthened in immunized animals in relation to the controls. The applied inoculum of this strain was much higher (505 x LD50) than the remaining ones. The protection conferred was evident; nevertheless, more data are needed to determine how relevant the results are to humans.

Complement C5a Receptor 1 Exacerbates the Pathophysiology of N. meningitidis Sepsis and Is a Potential Target for Disease Treatment

PubMed Central

Herrmann, Johannes B.; Muenstermann, Marcel; Strobel, Lea; Schubert-Unkmeir, Alexandra; Woodruff, Trent M.; Klos, Andreas

2018-01-01

ABSTRACT Sepsis caused by Neisseria meningitidis (meningococcus) is a rapidly progressing, life-threatening disease. Because its initial symptoms are rather unspecific, medical attention is often sought too late, i.e., when the systemic inflammatory response is already unleashed. This in turn limits the success of antibiotic treatment. The complement system is generally accepted as the most important innate immune determinant against invasive meningococcal disease since it protects the host through the bactericidal membrane attack complex. However, complement activation concomitantly liberates the C5a peptide, and it remains unclear whether this potent anaphylatoxin contributes to protection and/or drives the rapidly progressing immunopathogenesis associated with meningococcal disease. Here, we dissected the specific contribution of C5a receptor 1 (C5aR1), the canonical receptor for C5a, using a mouse model of meningococcal sepsis. Mice lacking C3 or C5 displayed susceptibility that was enhanced by >1,000-fold or 100-fold, respectively, consistent with the contribution of these components to protection. In clear contrast, C5ar1−/− mice resisted invasive meningococcal infection and cleared N. meningitidis more rapidly than wild-type (WT) animals. This favorable outcome stemmed from an ameliorated inflammatory cytokine response to N. meningitidis in C5ar1−/− mice in both in vivo and ex vivo whole-blood infections. In addition, inhibition of C5aR1 signaling without interference with the complement bactericidal activity reduced the inflammatory response also in human whole blood. Enticingly, pharmacologic C5aR1 blockade enhanced mouse survival and lowered meningococcal burden even when the treatment was administered after sepsis induction. Together, our findings demonstrate that C5aR1 drives the pathophysiology associated with meningococcal sepsis and provides a promising target for adjunctive therapy. PMID:29362231

Inactivation of NMB0419, Encoding a Sel1-Like Repeat (SLR) Protein, in Neisseria meningitidis Is Associated with Differential Expression of Genes Belonging to the Fur Regulon and Reduced Intraepithelial Replication

PubMed Central

Li, Ming-Shi

2017-01-01

ABSTRACT Neisseria meningitidis is a commensal microbe that colonizes the human nasopharynx but occasionally invades the bloodstream to cause life-threatening infection. N. meningitidis MC58 NMB0419 encodes a Sel1-like repeat (SLR)-containing protein, previously implicated in invasion of epithelial cells. A gene-regulatory function was revealed in Escherichia coli expressing plasmid-borne NMB0419 and showing significantly increased epithelial adherence compared to the wild type, due to increased expression of mannose-sensitive type 1 pili. While a meningococcal NMB0419 mutant did not have altered epithelial adherence, in a transcriptome-wide comparison of the wild type and an NMB0419 mutant, a large proportion of genes differentially regulated in the mutant were involved in iron acquisition and metabolism. Fifty-one percent and 38% of genes, respectively, up- and downregulated in the NMB0419 mutant had previously been identified as being induced and repressed by meningococcal Fur. An in vitro growth defect of the NMB0419 mutant under iron restriction was consistent with the downregulation of tbpAB and hmbR, while an intraepithelial replication defect was consistent with the downregulation of tonB, exbB, and exbD, based on a known phenotype of a meningococcal tonB mutant. Disruption of the N-terminal NMB0419 signal peptide, predicted to export the protein beyond the cytoplasmic membrane, resulted in loss of functional traits in N. meningitidis and E. coli. Our study indicates that the expression of NMB0419 is associated with transcriptional changes counterbalancing the regulatory function of Fur, offering a new perspective on regulatory mechanisms involved in meningococcal interaction with epithelial cells, and suggests new insights into the roles of SLR-containing genes in other bacteria. PMID:28264906

Clinical evaluation of a loop-mediated isothermal amplification (LAMP) assay for rapid detection of Neisseria meningitidis in cerebrospinal fluid.

PubMed

Lee, DoKyung; Kim, Eun Jin; Kilgore, Paul E; Kim, Soon Ae; Takahashi, Hideyuki; Ohnishi, Makoto; Anh, Dang Duc; Dong, Bai Qing; Kim, Jung Soo; Tomono, Jun; Miyamoto, Shigehiko; Notomi, Tsugunori; Kim, Dong Wook; Seki, Mitsuko

2015-01-01

Neisseria meningitidis (Nm) is a leading causative agent of bacterial meningitis in humans. Traditionally, meningococcal meningitis has been diagnosed by bacterial culture. However, isolation of bacteria from patients' cerebrospinal fluid (CSF) is time consuming and sometimes yields negative results. Recently, polymerase chain reaction (PCR)-based diagnostic methods of detecting Nm have been considered the gold standard because of their superior sensitivity and specificity compared with culture. In this study, we developed a loop-mediated isothermal amplification (LAMP) method and evaluated its ability to detect Nm in cerebrospinal fluid (CSF). We developed a meningococcal LAMP assay (Nm LAMP) that targets the ctrA gene. The primer specificity was validated using 16 strains of N. meningitidis (serogroup A, B, C, D, 29-E, W-135, X, Y, and Z) and 19 non-N. meningitidis species. Within 60 min, the Nm LAMP detected down to ten copies per reaction with sensitivity 1000-fold more than that of conventional PCR. The LAMP assays were evaluated using a set of 1574 randomly selected CSF specimens from children with suspected meningitis collected between 1998 and 2002 in Vietnam, China, and Korea. The LAMP method was shown to be more sensitive than PCR methods for CSF samples (31 CSF samples were positive by LAMP vs. 25 by PCR). The detection rate of the LAMP method was substantially higher than that of the PCR method. In a comparative analysis of the PCR and LAMP assays, the clinical sensitivity, specificity, positive predictive value, and negative predictive value of the LAMP assay were 100%, 99.6%, 80.6%, and 100%, respectively. Compared to PCR, LAMP detected Nm with higher analytical and clinical sensitivity. This sensitive and specific LAMP method offers significant advantages for screening patients on a population basis and for diagnosis in clinical settings.

Role of penA polymorphisms for penicillin susceptibility in Neisseria lactamica and Neisseria meningitidis.

PubMed

Karch, André; Vogel, Ulrich; Claus, Heike

2015-10-01

In meningococci, reduced penicillin susceptibility is associated with five specific mutations in the transpeptidase region of penicillin binding protein 2 (PBP2). We showed that the same set of mutations was present in 64 of 123 Neisseria lactamica strains obtained from a carriage study (MIC range: 0.125-2.0mg/L). The PBP2 encoding penA alleles in these strains were genetically similar to those found in intermediate resistant meningococci suggesting frequent interspecies genetic exchange. Fifty-six N. lactamica isolates with mostly lower penicillin MICs (range: 0.064-0.38mg/L) exhibited only three of the five mutations. The corresponding penA alleles were unique to N. lactamica and formed a distinct genetic clade. PenA alleles with no mutations on the other hand were unique to meningococci. Under penicillin selective pressure, genetic transformation of N. lactamica penA alleles in meningococci was only possible for alleles encoding five mutations, but not for those encoding three mutations; the transfer resulted in MICs comparable to those of meningococci harboring penA alleles that encoded PBP2 with five mutations, but considerably lower than those of the corresponding N. lactamica donor strains. Due to a transformation barrier the complete N. lactamica penA could not be transformed into N. meningitidis. In summary, penicillin MICs in N. lactamica were associated with the number of mutations in the transpeptidase region of PBP2. Evidence for interspecific genetic transfer was only observed for penA alleles associated with higher MICs, suggesting that alleles encoding only three mutations in the transpeptidase region are biologically not effective in N. meningitidis. Factors other than PBP2 seem to be responsible for the high levels of penicillin resistance in N. lactamica. A reduction of penicillin susceptibility in N. meningitidis by horizontal gene transfer from N. lactamica is unlikely to happen. Copyright © 2015 Elsevier GmbH. All rights reserved.

Use of Restriction Fragment Length Polymorphisms to Investigate Strain Variation Within Neisseria Meningitidis.

NASA Astrophysics Data System (ADS)

Williams, Shelley Diane

Similarity within bacterial populations is difficult to assess due to the limited number of characters available for evaluation and the heterogeneity of bacterial species. Currently, the preferred method used to evaluate the structure of bacterial populations is multilocus enzyme electrophoresis. However, this method is extremely cumbersome and only offers an indirect measure of genetic similarities. The development of a more direct and less cumbersome method for this purpose is warranted. Restriction fragment length polymorphism analysis was evaluated as a tool for use in the study of bacterial population structures and in the epidemiology and surveillance of infectious disease. A collection of Neisseria meningitidis was available for use in the investigation of this technique. Neisseria meningitidis is the causative agent of epidemic cerebrospinal meningitis and septicemia as well as a variety of other clinical manifestations. Each isolate in the collection was defined in terms of serogroup specificity, clinical history, geographic source, and date of isolation. Forty -six strains were chosen for this study. The DNA from each strain was restricted with Pst1 and EcoR1 and electrophoresed on agarose gels. The DNA was transferred to nylon filters and hybridized with P ^{32} labeled DNA probes. Two randomly generated probes and a gene-specific probe were used to estimate the genetic similarities between and among the strains in the study population. A total of 28 different restriction fragment migration types were detected by the probes used. Data obtained from the RFLP analysis was analysed by cluster analysis and multivariate statistical methods. A total of 7 clones groups were detected. Two of these appear to be major clones that comprise 35% of the population. This analysis demonstrates the lack of structure within Neisseria meningitidis due primarily to a heterogenous population and the lack of geographic segregation. The potential utility of this technique as a tool in epidemiologic surveillance is addressed. Further work is needed in the evaluation of RFLP analysis in the taxonomy bacteria.

[Endonasal endoscopic surgery in the treatment of spontaneous or post-traumatic cerebrospinal fluid (csf) leaks].

PubMed

Nallet, E; Decq, P; Bezzo, A; Le Lievre, G; Peynegre, R; Coste, A

1998-10-01

The incidence and the risk of meningitidis justify treatment in all cases of cerebrospinal fluid rhinorrhea with spontaneous etiology or after traumatic injury. Endonasal surgery with endoscopic instruments provides many advantages compared with transcranial or transfacial approach used by neurosurgeons. We report our experience and our surgical technique in the treatment of CSF leaks in 5 patients. Intrathecal injection of fluoresceine was very useful in all cases for detecting the CSF leak. Total or selected ethmoidectomy depended on the localization of the leakage. Wide sphenoidotomy enables detection and repair of CSF leaks from the sphenoid cavity. A free graft of inferior turbinal mucosal was used to repair the breache. This rapid low morbidity surgery offered secure closure of rhinorrhea in 4 cases after one procedure and in 1 case after two procedures with an average follow up of 22 months. Cerebrospinal fluid rhinorrhea can be managed in first line therapy with endoscopic intranasal surgical techniques when they are localized in the anterior ethmoid or in the sphenoid cavity.

Characteristics of a new meningococcal serogroup B vaccine, bivalent rLP2086 (MenB-FHbp; Trumenba®).

PubMed

Gandhi, Ashesh; Balmer, Paul; York, Laura J

2016-08-01

Neisseria meningitidis is a common cause of bacterial meningitis, often leading to permanent sequelae or death. N. meningitidis is classified into serogroups based on the composition of the bacterial capsular polysaccharide; the 6 major disease-causing serogroups are designated A, B, C, W, X, and Y. Four of the 6 disease-causing serogroups (A, C, Y, and W) can be effectively prevented with available quadrivalent capsular polysaccharide protein conjugate vaccines; however, capsular polysaccharide conjugate vaccines are not effective against meningococcal serogroup B (MnB). There is no vaccine available for serogroup X. The public health need for an effective serogroup B vaccine is evident, as MnB is the most common cause of meningococcal disease in the United States and is responsible for almost half of all cases in persons aged 17 to 22 years. In fact, serogroup B meningococci were responsible for the recent meningococcal disease outbreaks on college campuses. However, development of a suitable serogroup B vaccine has been challenging, as serogroup B polysaccharide-based vaccines were found to be poorly immunogenic. Vaccine development for MnB focused on identifying potential outer membrane protein targets that elicit broadly protective immune responses across strains from the vast number of proteins that exist on the bacterial surface. Human factor H binding protein (fHBP; also known as LP2086), a conserved surface-exposed bacterial lipoprotein, was identified as a promising vaccine candidate. Two recombinant protein-based serogroup B vaccines that contain fHBP have been successfully developed and licensed in the United States under an accelerated approval process: bivalent rLP2086 (MenB-FHbp; Trumenba®) and 4CMenB (MenB-4 C; Bexsero®). This review will focus on bivalent rLP2086 only, including vaccine components, mechanism of action, and potential coverage across serogroup B strains in the United States.

Sequence, distribution and chromosomal context of class I and class II pilin genes of Neisseria meningitidis identified in whole genome sequences

PubMed Central

2014-01-01

Background Neisseria meningitidis expresses type four pili (Tfp) which are important for colonisation and virulence. Tfp have been considered as one of the most variable structures on the bacterial surface due to high frequency gene conversion, resulting in amino acid sequence variation of the major pilin subunit (PilE). Meningococci express either a class I or a class II pilE gene and recent work has indicated that class II pilins do not undergo antigenic variation, as class II pilE genes encode conserved pilin subunits. The purpose of this work was to use whole genome sequences to further investigate the frequency and variability of the class II pilE genes in meningococcal isolate collections. Results We analysed over 600 publically available whole genome sequences of N. meningitidis isolates to determine the sequence and genomic organization of pilE. We confirmed that meningococcal strains belonging to a limited number of clonal complexes (ccs, namely cc1, cc5, cc8, cc11 and cc174) harbour a class II pilE gene which is conserved in terms of sequence and chromosomal context. We also identified pilS cassettes in all isolates with class II pilE, however, our analysis indicates that these do not serve as donor sequences for pilE/pilS recombination. Furthermore, our work reveals that the class II pilE locus lacks the DNA sequence motifs that enable (G4) or enhance (Sma/Cla repeat) pilin antigenic variation. Finally, through analysis of pilin genes in commensal Neisseria species we found that meningococcal class II pilE genes are closely related to pilE from Neisseria lactamica and Neisseria polysaccharea, suggesting horizontal transfer among these species. Conclusions Class II pilins can be defined by their amino acid sequence and genomic context and are present in meningococcal isolates which have persisted and spread globally. The absence of G4 and Sma/Cla sequences adjacent to the class II pilE genes is consistent with the lack of pilin subunit variation in these isolates, although horizontal transfer may generate class II pilin diversity. This study supports the suggestion that high frequency antigenic variation of pilin is not universal in pathogenic Neisseria. PMID:24690385

Genotypic and phenotypic characterization of the O-linked protein glycosylation system reveals high glycan diversity in paired meningococcal carriage isolates.

PubMed

Børud, Bente; Bårnes, Guro K; Brynildsrud, Ola Brønstad; Fritzsønn, Elisabeth; Caugant, Dominique A

2018-03-19

Species within the genus Neisseria display significant glycan diversity associated with the O -linked protein glycosylation ( pgl ) systems due to phase variation, polymorphic genes and gene content. The aim of this study was to examine in detail the pgl genotype and glycosylation phenotype in meningococcal isolates and the changes occurring during short-term asymptomatic carriage. Paired meningococcal isolates derived from 50 asymptomatic meningococcal carriers, taken about two months apart, were analyzed with whole genome sequencing. The O -linked protein glycosylation genes were characterized in detail using the Genome Comparator tool at the PubMLST.org database. Immunoblotting with glycan specific antibodies were used to investigate the protein glycosylation phenotype. All major pgl locus polymorphisms identified in N. meningitidis to date were present in our isolate collection, with the variable presence of pglG-pglH, both in combination with either pglB or pglB2. We identified significant changes and diversity in the pgl genotype and/or glycan phenotype in 96% of the paired isolates. There was also a high degree of glycan microheterogeneity, in which different variants of glycan structures were found at a given glycoprotein. The main mechanism responsible for the observed differences was phase variable expression of the involved glycosyltransferases and the O-acetyltransferase. To our knowledge, this is the first characterization of the pgl genotype and glycosylation phenotype in a larger strain collection. This study thus provides important insight into glycan diversity in N. meningitidis and phase variability changes that influence the expressed glycoform repertoire during meningococcal carriage. Importance Bacterial meningitis is a serious global health problem and one of the major causative organisms is Neisseria meningitidis , which is also a common commensal in the upper respiratory tract of healthy humans. In bacteria, numerous loci involved in biosynthesis of surface exposed antigenic structures that are involved in the interaction between bacteria and host, are frequently subjected to homologous recombination and phase variation. These mechanisms are well described in Neisseria, and phase variation provides the ability to change these structures reversibly in response to the environment. Protein glycosylation systems are becoming widely identified in bacteria, yet little is known about the mechanisms and evolutionary forces influencing glycan composition during carriage and disease. Copyright © 2018 American Society for Microbiology.

Meningococcal serogroup Y emergence in Europe

PubMed Central

Bröker, Michael; Bukovski, Suzana; Culic, Davor; Jacobsson, Susanne; Koliou, Maria; Kuusi, Markku; Simões, Maria João; Skoczynska, Anna; Toropainen, Maija; Taha, Muhamed-Keir; Tzanakaki, Georgina

2014-01-01

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal.1,2 Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low. PMID:24608912

Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease.

PubMed

Caugant, D A; Frøholm, L O; Bøvre, K; Holten, E; Frasch, C E; Mocca, L F; Zollinger, W D; Selander, R K

1986-07-01

Strains of Neisseria meningitidis responsible for an epidemic of meningococcal disease occurring in Norway since the mid-1970s and for recent increases in the incidence of disease in several other parts of Europe have been identified by multilocus enzyme electrophoresis as members of a distinctive group of 22 closely related clones (the ET-5 complex). Clones of this complex have also colonized South Africa, Chile, Cuba, and Florida, where they have been identified as the causative agents of recent outbreaks of meningococcal disease. There is strong circumstantial evidence that outbreaks of disease occurring in Miami in 1981 and 1982 were caused in large part by bacteria that reached Florida via human immigrants from Cuba.

Invasive bacterial diseases: national surveillance in Italy and vaccination coverage in the Local Health Agency 4 "Chiavarese", Liguria region (Italy).

PubMed

Trucchi, C; Zoppi, G

2012-06-01

In 2007 in Italy, the National Institute of Health published a new protocol for the National Surveillance of Invasive Bacterial Diseases, in order to enhance the notification system of these diseases and to improve immunization strategies. Available vaccines to prevent these diseases were introduced for the first time into the 1999-2000 National Immunization Plan (NIP) (vaccination against Haemophilus influenzae type b) and the 2005-2007 NIP (vaccination against Streptococcus pneumoniae and Neisseria meningitidis serogroup C). We evaluated the frequency of invasive diseases, on the basis of the number of notifications, the different immunization strategies in the Italian Regions and the vaccination coverage in Local Health Agency 4 "Chiavarese" (LHA) in the Liguria Region (Italy). We evaluated the number of notifications of invasive diseases collected by the national databank coordinated by the ISS (Informative System of Infectious Diseases, SIMI) from 1994 to 2011. We also examined regional regulations concerning immunization policies. Immunization coverage was calculated by means of the "OASIS" software (version 9.0.0) used in our LHA. Available data indicate that the large-scale vaccination policy begun in 1999 in Italy has led to a great reduction in Haemophilus influenzae-related diseases in the pediatric age. Meningococcal diseases have declined to a lesser degree; this is due to the more recent introduction of vaccination against serogroup C (in 2005), the variability of the immunization strategies adopted in the different Italian Regions and the availability of the vaccination against serogroup C only in the pediatric age. The diseases caused by Streptococcus pneumoniae seem to have increased since 2007 because of the implementation of the Surveillance of Invasive Diseases Program and the subsequent notification of all invasive diseases (not only meningitis). Furthermore, the various Italian Regions have adopted different immunization strategies against this disease, too. We evaluated vaccination coverage in LHA 4 from 2003 to 2008. VC levels against Haemophilus influenzae are excellent; the objective indicated in the 2005-2007 NIP (> or = 95%) has therefore been reached. Vaccination coverage levels against Streptococcus pneumoniae and Neisseria meningitidis serogroup C at the 24th month of age are also good. However, we need to implement specific immunization strategies for adolescents, since the vaccination coverage levels are not completely satisfactory. The improvement of the national invasive disease surveillance system has provided better knowledge of the size of the problem and the impact of immunization strategies on the incidence of invasive bacterial diseases. Furthermore, immunization policies in Italy display territorial heterogeneity. Vaccination coverage levels against Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis at the 24th month in LHA 4 are very high. In adolescents (15 year-olds) the immunization coverage are good but needs to be improved through specific strategies, such as raising the awareness of healthcare workers, involving general practitioners and educating the target population.

Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood–brain barrier

PubMed Central

Mairey, Emilie; Genovesio, Auguste; Donnadieu, Emmanuel; Bernard, Christine; Jaubert, Francis; Pinard, Elisabeth; Seylaz, Jacques; Olivo-Marin, Jean-Christophe; Nassif, Xavier; Duménil, Guillaume

2006-01-01

Neisseria meningitidis is a commensal bacterium of the human nasopharynx. Occasionally, this bacterium reaches the bloodstream and causes meningitis after crossing the blood–brain barrier by an unknown mechanism. An immunohistological study of a meningococcal sepsis case revealed that neisserial adhesion was restricted to capillaries located in low blood flow regions in the infected organs. This study led to the hypothesis that drag forces encountered by the meningococcus in the bloodstream determine its attachment site in vessels. We therefore investigated the ability of N. meningitidis to bind to endothelial cells in the presence of liquid flow mimicking the bloodstream with a laminar flow chamber. Strikingly, average blood flows reported for various organs strongly inhibited initial adhesion. As cerebral microcirculation is known to be highly heterogeneous, cerebral blood velocity was investigated at the level of individual vessels using intravital imaging of rat brain. In agreement with the histological study, shear stress levels compatible with meningococcal adhesion were only observed in capillaries, which exhibited transient reductions in flow. The flow chamber assay revealed that, after initial attachment, bacteria resisted high blood velocities and even multiplied, forming microcolonies resembling those observed in the septicemia case. These results argue that the combined mechanical properties of neisserial adhesion and blood microcirculation target meningococci to transiently underperfused cerebral capillaries and thus determine disease development. PMID:16864659

Strong positive selection and recombination drive the antigenic variation of the PilE protein of the human pathogen Neisseria meningitidis.

PubMed

Andrews, T Daniel; Gojobori, Takashi

2004-01-01

The PilE protein is the major component of the Neisseria meningitidis pilus, which is encoded by the pilE/pilS locus that includes an expressed gene and eight homologous silent fragments. The silent gene fragments have been shown to recombine through gene conversion with the expressed gene and thereby provide a means by which novel antigenic variants of the PilE protein can be generated. We have analyzed the evolutionary rate of the pilE gene using the nucleotide sequence of two complete pilE/pilS loci. The very high rate of evolution displayed by the PilE protein appears driven by both recombination and positive selection. Within the semivariable region of the pilE and pilS genes, recombination appears to occur within multiple small sequence blocks that lie between conserved sequence elements. Within the hypervariable region, positive selection was identified from comparison of the silent and expressed genes. The unusual gene conversion mechanism that operates at the pilE/pilS locus is a strategy employed by N. meningitidis to enhance mutation of certain regions of the PilE protein. The silent copies of the gene effectively allow "parallelized" evolution of pilE, thus enabling the encoded protein to rapidly explore a large area of sequence space in an effort to find novel antigenic variants.

Multiplexed instrument-free meningitis diagnosis on a polymer/paper hybrid microfluidic biochip.

PubMed

Dou, Maowei; Sanjay, Sharma T; Dominguez, Delfina C; Liu, Peng; Xu, Feng; Li, XiuJun

2017-01-15

Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Haemophilus influenzae type b (Hib) are three most common pathogens accounting for most bacterial meningitis, a serious global infectious disease with high fatality, especially in developing nations. Because the treatment and antibiotics differ among each type, the identification of the exact bacteria causing the disease is vital. Herein, we report a polymer/paper hybrid microfluidic biochip integrated with loop-mediated isothermal amplification (LAMP) for multiplexed instrument-free diagnosis of these three major types of bacterial meningitis, with high sensitivity and specificity. Results can be visually observed by the naked eye or imaged by a smartphone camera under a portable UV light source. Without using any specialized laboratory instrument, the limits of detection of a few DNA copies per LAMP zone for N. meningitidis, S. pneumoniae and Hib were achieved within 1h. In addition, these three types of microorganisms spiked in artificial cerebrospinal fluid (ACSF) were directly detected simultaneously, avoiding cumbersome sample preparation procedures in conventional methods. Compared with the paper-free non-hybrid microfluidic biochip over a period of three months, the hybrid microfluidic biochip was found to have a much longer shelf life. Hence, this rapid, instrument-free and highly sensitive microfluidic approach has great potential for point-of-care (POC) diagnosis of multiple infectious diseases simultaneously, especially in resource-limited settings. Copyright © 2016 Elsevier B.V. All rights reserved.

rmpM genosensor for detection of human brain bacterial meningitis in cerebrospinal fluid.

PubMed

Dash, Sandip Kumar; Sharma, Minakshi; Khare, Shashi; Kumar, Ashok

2013-09-01

Human brain bacterial meningitis is a life-threatening disease caused mainly by Neisseria meningitidis, lead to damage of the outer membrane covering (meninges) of brain or even death. The usual methods of diagnosis are either time-consuming or have some limitations. The specific rmpM (reduction-modifiable protein M) virulent gene based genosensor is more sensitive, specific, and can detect N. meningitidis directly from the patient cerebrospinal fluid in 30 min including 1-min response time. 5'-Thiol-labeled single-stranded DNA (ssDNA) probe was immobilized onto screen-printed gold electrode (SPGE) and hybridized with denatured (95 °C) single-stranded genomic DNA (ssG-DNA) for 10 min at 25 °C. The electrochemical response was measured by cyclic voltammetry, differential pulse voltammetry (DPV) and electrochemical impedance using redox indicators. The sensitivity of the genosensor was 9.5087 (μA/cm(2))/ng with DPV and limit of detection was 3 ng/6 μL ssG-DNA. The immobilization of the ssDNA probe and hybridization with ssG-DNA from N. meningitidis was characterized by atomic force microscopy and Fourier transform infrared spectroscopy. The rmpM genosensor was stable for 6 months at 4 °C with 10 % loss in initial DPV current. The advantage of rmpM genosensor is to detect bacterial meningitis simultaneously in multiple patients using SPGE array during an outbreak of the disease.

Serogroup and Clonal Characterization of Czech Invasive Neisseria meningitidis Strains Isolated from 1971 to 2015

PubMed Central

Jandova, Zuzana; Musilek, Martin; Vackova, Zuzana; Kozakova, Jana; Krizova, Pavla

2016-01-01

Background This study presents antigenic and genetic characteristics of Neisseria meningitidis strains recovered from invasive meningococcal disease (IMD) in the Czech Republic in 1971–2015. Material and Methods A total of 1970 isolates from IMD, referred to the National Reference Laboratory for Meningococcal Infections in 1971–2015, were studied. All isolates were identified and characterized by conventional biochemical and serological tests. Most isolates (82.5%) were characterized by multilocus sequence typing method. Results In the study period 1971–2015, the leading serogroup was B (52.4%), most often assigned to clonal complexes cc32, cc41/44, cc18, and cc269. A significant percentage of strains were of serogroup C (41.4%), with high clonal homogeneity due to hyperinvasive complex cc11, which played an important role in IMD in the Czech Republic in the mid-1990s. Serogroup Y isolates, mostly assigned to cc23, and isolates of clonally homogeneous serogroup W have also been recovered more often over the last years. Conclusion The incidence of IMD and distribution of serogroups and clonal complexes of N. meningitidis in the Czech Republic varied over time, as can be seen from the long-term monitoring, including molecular surveillance data. Data from the conventional and molecular IMD surveillance are helpful in refining the antimeningococcal vaccination strategy in the Czech Republic. PMID:27936105

Duplex recombinase polymerase amplification assays incorporating competitive internal controls for bacterial meningitis detection.

PubMed

Higgins, Owen; Clancy, Eoin; Forrest, Matthew S; Piepenburg, Olaf; Cormican, Martin; Boo, Teck Wee; O'Sullivan, Nicola; McGuinness, Claire; Cafferty, Deirdre; Cunney, Robert; Smith, Terry J

2018-04-01

Recombinase polymerase amplification (RPA) is an isothermal nucleic acid amplification technology that provides rapid and robust infectious disease pathogen detection, ideal for point-of-care (POC) diagnostics in disease-prevalent low-resource countries. We have developed and evaluated three duplex RPA assays incorporating competitive internal controls for the detection of leading bacterial meningitis pathogens. Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae singleplex RPA assays were initially developed and evaluated, demonstrating 100% specificity with limits of detection of 4.1, 8.5 and 3.9 genome copies per reaction, respectively. Each assay was further developed into internally controlled duplex RPA assays via the incorporation of internal amplification control templates. Clinical performance of each internally controlled duplex RPA assay was evaluated by testing 64 archived PCR-positive clinical samples. Compared to real-time PCR, all duplex RPA assays demonstrated 100% diagnostic specificity, with diagnostic sensitivities of 100%, 86.3% and 100% for the S. pneumoniae, N. meningitidis and H. influenzae assays, respectively. This study details the first report of internally controlled duplex RPA assays for the detection of bacterial meningitis pathogens: S. pneumoniae, N. meningitidis and H. influenzae. We have successfully demonstrated the clinical diagnostic utility of each duplex RPA assay, introducing effective diagnostic technology for POC bacterial meningitis identification in disease-prevalent developing countries. Copyright © 2018 Elsevier Inc. All rights reserved.

Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage*

PubMed Central

John, Constance M.; Phillips, Nancy J.; Din, Richard; Liu, Mingfeng; Rosenqvist, Einar; Høiby, E. Arne; Stein, Daniel C.; Jarvis, Gary A.

2016-01-01

The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1–3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-α in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections. PMID:26655715

Structural and Functional Features of a Developmentally Regulated Lipopolysaccharide-Binding Protein

PubMed Central

Krasity, Benjamin C.; Troll, Joshua V.; Lehnert, Erik M.; Hackett, Kathleen T.; Dillard, Joseph P.; Apicella, Michael A.; Goldman, William E.

2015-01-01

ABSTRACT Mammalian lipopolysaccharide (LPS) binding proteins (LBPs) occur mainly in extracellular fluids and promote LPS delivery to specific host cell receptors. The function of LBPs has been studied principally in the context of host defense; the possible role of LBPs in nonpathogenic host-microbe interactions has not been well characterized. Using the Euprymna scolopes-Vibrio fischeri model, we analyzed the structure and function of an LBP family protein, E. scolopes LBP1 (EsLBP1), and provide evidence for its role in triggering a symbiont-induced host developmental program. Previous studies showed that, during initial host colonization, the LPS of V. fischeri synergizes with peptidoglycan (PGN) monomer to induce morphogenesis of epithelial tissues of the host animal. Computationally modeled EsLBP1 shares some but not all structural features of mammalian LBPs that are thought important for LPS binding. Similar to human LBP, recombinant EsLBP1 expressed in insect cells bound V. fischeri LPS and Neisseria meningitidis lipooligosaccharide (LOS) with nanomolar or greater affinity but bound Francisella tularensis LPS only weakly and did not bind PGN monomer. Unlike human LBP, EsLBP1 did not bind N. meningitidis LOS:CD14 complexes. The eslbp1 transcript was upregulated ~22-fold by V. fischeri at 24 h postinoculation. Surprisingly, this upregulation was not induced by exposure to LPS but, rather, to the PGN monomer alone. Hybridization chain reaction-fluorescent in situ hybridization (HCR-FISH) and immunocytochemistry (ICC) localized eslbp1 transcript and protein in crypt epithelia, where V. fischeri induces morphogenesis. The data presented here provide a window into the evolution of LBPs and the scope of their roles in animal symbioses. PMID:26463160

Naturally Occurring Lipid A Mutants in Neisseria meningitidis from Patients with Invasive Meningococcal Disease Are Associated with Reduced Coagulopathy

PubMed Central

Fransen, Floris; Heckenberg, Sebastiaan G. B.; Hamstra, Hendrik Jan; Feller, Moniek; Boog, Claire J. P.; van Putten, Jos P. M.; van de Beek, Diederik

2009-01-01

Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial outer membrane, is sensed by mammalian cells through Toll-like receptor 4 (TLR4), resulting in activation of proinflammatory cytokine pathways. TLR4 recognizes the lipid A moiety of the LPS molecule, and the chemical composition of the lipid A determines how well it is recognized by TLR4. N. meningitidis has been reported to produce lipid A with six acyl chains, the optimal number for TLR4 recognition. Indeed, meningococcal sepsis is generally seen as the prototypical endotoxin-mediated disease. In the present study, we screened meningococcal disease isolates from 464 patients for their ability to induce cytokine production in vitro. We found that around 9% of them were dramatically less potent than wild-type strains. Analysis of the lipid A of several of the low-activity strains by mass spectrometry revealed they were penta-acylated, suggesting a mutation in the lpxL1 or lpxL2 genes required for addition of secondary acyl chains. Sequencing of these genes showed that all the low activity strains had mutations that inactivated the lpxL1 gene. In order to see whether lpxL1 mutants might give a different clinical picture, we investigated the clinical correlate of these mutations in a prospective nationwide observational cohort study of adults with meningococcal meningitis. Patients infected with an lpxL1 mutant presented significantly less frequently with rash and had higher thrombocyte counts, consistent with reduced cytokine induction and less activation of tissue-factor mediated coagulopathy. In conclusion, here we report for the first time that a surprisingly large fraction of meningococcal clinical isolates have LPS with underacylated lipid A due to mutations in the lpxL1 gene. The resulting low-activity LPS may have an important role in virulence by aiding the bacteria to evade the innate immune system. Our results provide the first example of a specific mutation in N. meningitidis that can be correlated with the clinical course of meningococcal disease. PMID:19390612

Comparative effects of carrier proteins on vaccine-induced immune response.

PubMed

Knuf, Markus; Kowalzik, Frank; Kieninger, Dorothee

2011-07-12

The efficacy of vaccines against major encapsulated bacterial pathogens -Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b (Hib) - has been significantly enhanced by conjugating the respective polysaccharides with different carrier proteins: diphtheria toxoid; non-toxic cross-reactive material of diphtheria toxin(197), tetanus toxoid, N. meningitidis outer membrane protein, and non-typeable H. influenzae-derived protein D. Hib, meningococcal, and pneumococcal conjugate vaccines have shown good safety and immunogenicity profiles regardless of the carrier protein used, although data are conflicting as to which carrier protein is the most immunogenic. Coadministration of conjugate vaccines bearing the same carrier protein has the potential for inducing either positive or negative effects on vaccine immunogenicity (immune interference). Clinical studies on the coadministration of conjugate vaccines reveal conflicting data with respect to immune interference and vaccine efficacy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Parameter and state estimation in a Neisseria meningitidis model: A study case of Niger

NASA Astrophysics Data System (ADS)

Bowong, S.; Mountaga, L.; Bah, A.; Tewa, J. J.; Kurths, J.

2016-12-01

Neisseria meningitidis (Nm) is a major cause of bacterial meningitidis outbreaks in Africa and the Middle East. The availability of yearly reported meningitis cases in the African meningitis belt offers the opportunity to analyze the transmission dynamics and the impact of control strategies. In this paper, we propose a method for the estimation of state variables that are not accessible to measurements and an unknown parameter in a Nm model. We suppose that the yearly number of Nm induced mortality and the total population are known inputs, which can be obtained from data, and the yearly number of new Nm cases is the model output. We also suppose that the Nm transmission rate is an unknown parameter. We first show how the recruitment rate into the population can be estimated using real data of the total population and Nm induced mortality. Then, we use an auxiliary system called observer whose solutions converge exponentially to those of the original model. This observer does not use the unknown infection transmission rate but only uses the known inputs and the model output. This allows us to estimate unmeasured state variables such as the number of carriers that play an important role in the transmission of the infection and the total number of infected individuals within a human community. Finally, we also provide a simple method to estimate the unknown Nm transmission rate. In order to validate the estimation results, numerical simulations are conducted using real data of Niger.

A prolonged outbreak of invasive meningococcal disease in an extended Irish Traveller family across three Health Service Executive (HSE) areas in Ireland, 2010 to 2013.

PubMed

O'Connor, L; Ward, M; Bennett, D; Mulhall, R; O'Lorcain, P; Cunney, R; McDermott, R; Neville, E; Heslin, J; FitzGerald, R; Meyler, K; Conlon, M; Clarke, A; Corcoran, B; Fitzpatrick, G; O'Connor, B; Flanagan, P; O'Flanagan, D; Cotter, S

2015-05-28

Between March 2010 and November 2013 eight laboratory-confirmed cases of serogroup B, invasive meningococcal disease (IMD) were identified in an extended Irish Traveller family across three Health Service Executive (HSE) areas of Ireland. Cases were aged between 5 and 46 months, and were either a cousin or sibling of another case. All eight cases survived. Chemoprophylaxis was given to relevant nuclear family members and close contacts on each occasion, but failed to prevent further cases. Neisseria meningitidis isolates from six cases were highly related, belonging to the ST-41/44 clonal complex, and shared the porA designation 7–2,4. In November 2013, the outbreak control team recommended that directly observed ciprofloxacin chemoprophylaxis be administered simultaneously to the extended family, and that the four component meningococcal B (4CMenB) vaccine be administered to family members aged 2 months to 23 years inclusive and relevant close contacts of the eighth case. Subsequently these recommendations were implemented at three regional clinics. Additionally pharyngeal swabs (n=112) were collected to assess carriage rates of N. meningitidis in this extended family. Pharyngeal carriage of N. meningitidis was detected in 15 (13%) family members. From the epidemiological investigation and carriage study overcrowding was the most likely risk factor identified in this outbreak. To date, the combination of directly observed ciprofloxacin chemoprophylaxis and use of 4CMenB vaccine have controlled the outbreak with no further cases diagnosed.

A bacterial siren song: intimate interactions between neutrophils and pathogenic Neisseria

PubMed Central

Criss, Alison K.; Seifert, H. Steven

2012-01-01

Preface Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that are exquisitely adapted for growth at human mucosal surfaces and for efficient transmission between hosts. One factor that is essential to neisserial pathogenesis is the interaction between the bacteria and neutrophils, which are recruited in high numbers during infection. Although this vigorous host response could simply reflect effective immune recognition of the bacteria, there is mounting evidence that in fact these obligate human pathogens manipulate the innate immune response to promote infectious processes. This Review summarizes the mechanisms used by pathogenic neisseriae to resist and modulate the antimicrobial activities of neutrophils. It also details some of the major outstanding questions about the Neisseria–neutrophil relationship and proposes potential benefits of this relationship for the pathogen. PMID:22290508

Whole genome typing of the recently emerged Canadian serogroup W Neisseria meningitidis sequence type 11 clonal complex isolates associated with invasive meningococcal disease.

PubMed

Tsang, Raymond S W; Ahmad, Tauqeer; Tyler, Shaun; Lefebvre, Brigitte; Deeks, Shelley L; Gilca, Rodica; Hoang, Linda; Tyrrell, Gregory; Van Caeseele, Paul; Van Domselaar, Gary; Jamieson, Frances B

2018-04-01

This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW) sequence type 11 (ST-11) clonal complex (CC) isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC) ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

PubMed Central

Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.

2014-01-01

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N- or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (−LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not Δmip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines. PMID:25452551

Use of a Molecular Decoy to Segregate Transport from Antigenicity in the FrpB Iron Transporter from Neisseria meningitidis

PubMed Central

Saleem, Muhammad; Prince, Stephen M.; Rigby, Stephen E. J.; Imran, Muhammad; Patel, Hema; Chan, Hannah; Sanders, Holly; Maiden, Martin C. J.; Feavers, Ian M.; Derrick, Jeremy P.

2013-01-01

FrpB is an outer membrane transporter from Neisseria meningitidis, the causative agent of meningococcal meningitis. It is a member of the TonB-dependent transporter (TBDT) family and is responsible for iron uptake into the periplasm. FrpB is subject to a high degree of antigenic variation, principally through a region of hypervariable sequence exposed at the cell surface. From the crystal structures of two FrpB antigenic variants, we identify a bound ferric ion within the structure which induces structural changes on binding which are consistent with it being the transported substrate. Binding experiments, followed by elemental analysis, verified that FrpB binds Fe3+ with high affinity. EPR spectra of the bound Fe3+ ion confirmed that its chemical environment was consistent with that observed in the crystal structure. Fe3+ binding was reduced or abolished on mutation of the Fe3+-chelating residues. FrpB orthologs were identified in other Gram-negative bacteria which showed absolute conservation of the coordinating residues, suggesting the existence of a specific TBDT sub-family dedicated to the transport of Fe3+. The region of antigenic hypervariability lies in a separate, external sub-domain, whose structure is conserved in both the F3-3 and F5-1 variants, despite their sequence divergence. We conclude that the antigenic sub-domain has arisen separately as a result of immune selection pressure to distract the immune response from the primary transport function. This would enable FrpB to function as a transporter independently of antibody binding, by using the antigenic sub-domain as a ‘molecular decoy’ to distract immune surveillance. PMID:23457610

Use of a molecular decoy to segregate transport from antigenicity in the FrpB iron transporter from Neisseria meningitidis.

PubMed

Saleem, Muhammad; Prince, Stephen M; Rigby, Stephen E J; Imran, Muhammad; Patel, Hema; Chan, Hannah; Sanders, Holly; Maiden, Martin C J; Feavers, Ian M; Derrick, Jeremy P

2013-01-01

FrpB is an outer membrane transporter from Neisseria meningitidis, the causative agent of meningococcal meningitis. It is a member of the TonB-dependent transporter (TBDT) family and is responsible for iron uptake into the periplasm. FrpB is subject to a high degree of antigenic variation, principally through a region of hypervariable sequence exposed at the cell surface. From the crystal structures of two FrpB antigenic variants, we identify a bound ferric ion within the structure which induces structural changes on binding which are consistent with it being the transported substrate. Binding experiments, followed by elemental analysis, verified that FrpB binds Fe(3+) with high affinity. EPR spectra of the bound Fe(3+) ion confirmed that its chemical environment was consistent with that observed in the crystal structure. Fe(3+) binding was reduced or abolished on mutation of the Fe(3+)-chelating residues. FrpB orthologs were identified in other Gram-negative bacteria which showed absolute conservation of the coordinating residues, suggesting the existence of a specific TBDT sub-family dedicated to the transport of Fe(3+). The region of antigenic hypervariability lies in a separate, external sub-domain, whose structure is conserved in both the F3-3 and F5-1 variants, despite their sequence divergence. We conclude that the antigenic sub-domain has arisen separately as a result of immune selection pressure to distract the immune response from the primary transport function. This would enable FrpB to function as a transporter independently of antibody binding, by using the antigenic sub-domain as a 'molecular decoy' to distract immune surveillance.

Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function.

PubMed

Steeghs, Liana; van Vliet, Sandra J; Uronen-Hansson, Heli; van Mourik, Andries; Engering, Anneke; Sanchez-Hernandez, Martha; Klein, Nigel; Callard, Robin; van Putten, Jos P M; van der Ley, Peter; van Kooyk, Yvette; van de Winkel, Jan G J

2006-02-01

Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T-cell responses driven by DC towards T helper type 1 activity. Thus, the use of lgtB LPS may provide a powerful instrument to selectively induce the desired arm of the immune response and potentially increase vaccine efficacy.

Neisseria meningitidis; clones, carriage, and disease.

PubMed

Read, R C

2014-05-01

Neisseria meningitidis, the cause of meningococcal disease, has been the subject of sophisticated molecular epidemiological investigation as a consequence of the significant public health threat posed by this organism. The use of multilocus sequence typing and whole genome sequencing classifies the organism into clonal complexes. Extensive phenotypic, genotypic and epidemiological information is available on the PubMLST website. The human nasopharynx is the sole ecological niche of this species, and carrier isolates show extensive genetic diversity as compared with hyperinvasive lineages. Horizontal gene exchange and recombinant events within the meningococcal genome during residence in the human nasopharynx result in antigenic diversity even within clonal complexes, so that individual clones may express, for example, more than one capsular polysaccharide (serogroup). Successful clones are capable of wide global dissemination, and may be associated with explosive epidemics of invasive disease. © 2014 The Author Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Innate immune recognition and inflammation in Neisseria meningitidis infection.

PubMed

Johswich, Kay

2017-03-01

Neisseria meningitidis (Nme) can cause meningitis and sepsis, diseases which are characterised by an overwhelming inflammatory response. Inflammation is triggered by host pattern recognition receptors (PRRs) which are activated by pathogen-associated molecular patterns (PAMPs). Nme contains multiple PAMPs including lipooligosaccharide, peptidoglycan, proteins and metabolites. Various classes of PRRs including Toll-like receptors, NOD-like receptors, C-type lectins, scavenger receptors, pentraxins and others are expressed by the host to respond to any given microbe. While Toll-like receptors and NOD-like receptors are pivotal in triggering inflammation, other PRRs act as modulators of inflammation or aid in functional antimicrobial responses such as phagocytosis or complement activation. This review aims to give an overview of the various Nme PAMPs reported to date, the PRRs they activate and their implications during the inflammatory response to infection. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A probable prehistoric case of meningococcal disease from San Francisco Bay: Next generation sequencing of Neisseria meningitidis from dental calculus and osteological evidence.

PubMed

Eerkens, Jelmer W; Nichols, Ruth V; Murray, Gemma G R; Perez, Katherine; Murga, Engel; Kaijankoski, Phil; Rosenthal, Jeffrey S; Engbring, Laurel; Shapiro, Beth

2018-05-25

Next Generation Sequencing (NGS) of ancient dental calculus samples from a prehistoric site in San Francisco Bay, CA-SCL-919, reveals a wide range of potentially pathogenic bacteria. One older adult woman, in particular, had high levels of Neisseria meningitidis and low levels of Haemophilus influenzae, species that were not observed in the calculus from three other individuals. Combined with the presence of incipient endocranial lesions and pronounced meningeal grooves, we interpret this as an ancient case of meningococcal disease. This disease afflicts millions around the globe today, but little is known about its (pre)history. With additional sampling, we suggest NGS of calculus offers an exciting new window into the evolutionary history of these bacterial species and their interactions with humans. Copyright © 2018 Elsevier Inc. All rights reserved.

[Real-time PCR detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae DNA in clinical specimens].

PubMed

Vacková, Z; Lžičařová, D; Stock, N K; Kozáková, J

2015-10-01

The study aim was to implement a molecular real-time polymerase chain reaction (PCR) assay recommended by the CDC (Centers for Disease Control and Prevention) for the detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in clinical (culture negative) specimens from patients with suspected invasive bacterial disease. Clinical specimens are referred to the National Reference Laboratory (NRL) for Meningococcal Infections, Unit for Airborne Bacterial Infections, Centre for Epidemiology and Microbiology, National Institute of Public Health from various regions of the Czech Republic. Clinical specimens are, in particular, cerebrospinal fluid, anti-coagulated blood or serum and, exceptionally, post-mortem specimens. The NRL has implemented molecular diagnosis of these bacterial pathogens involved in meningitis and sepsis from clinical specimens since 1999. The first diagnostic method was semi-nested PCR followed by electrophoretic analysis. In 2014, a molecular qualitative real-time PCR assay was implemented.

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis

PubMed Central

Lu, Duo; Silhan, Jan; MacDonald, James T.; Carpenter, Elisabeth P.; Jensen, Kirsten; Tang, Christoph M.; Baldwin, Geoff S.; Freemont, Paul S.

2012-01-01

Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5′ to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures. PMID:23035246

Vaccine preventable meningitis in Malaysia: epidemiology and management.

PubMed

McNeil, Hannah C; Jefferies, Johanna M C; Clarke, Stuart C

2015-06-01

Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9-25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis.

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease.

PubMed

Granoff, Dan M

2009-06-24

Killing of Neisseria meningitidis can result from complement-mediated serum bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers > or =1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers > or =1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease.

Relative importance of complement-mediated bactericidal and opsonic activity for protection against meningococcal disease

PubMed Central

Granoff, Dan M.

2009-01-01

Killing of Neisseria meningitidis can result from complement-mediated bactericidal activity (SBA) or opsonophagocytosis (OPA), or a combination of the two mechanisms. While SBA titers ≥1:4 confer protection, recent evidence suggests that this threshold titer may not be required. For example, the incidence of meningococcal disease declines between ages 1 and 4 years without evidence of acquisition of SBA titers ≥1:4. Meningococcal polysaccharide vaccination also elicited OPA and lowered the risk of disease in patients with late complement component deficiencies whose sera did not support SBA. Sera from healthy adults immunized with an outer membrane vesicle vaccine showed OPA killing of N. meningitidis with C6-depleted complement, and whole blood from complement-sufficient non-immunized adults with SBA titers <1:4 also frequently had killing activity. Collectively the data indicate that SBA titers <1:4 and/or vaccine-induced OPA can confer protection against meningococcal disease. PMID:19477054

Detection of Haemophilus influenzae type b, Streptococcus agalactiae, Streptococcus pneumoniae and Neisseria meningitidis in CSF specimens of children suspicious of Meningitis in Ahvaz, Iran.

PubMed

Amin, Mansour; Ghaderpanah, Mozhgan; Navidifar, Tahereh

2016-10-01

Meningitis is a life-threatening infection associated with a high mortality and morbidity worldwide. Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae are the most prevalent infectious agents that cause bacterial meningitis (BM). The objective of this study was to determine the frequencies of these three bacteria using bacterial cultures and polymerase chain reaction (PCR). In our cross-sectional study, cerebrospinal fluid (CSF) specimens were obtained from 196 patients who were suspected of having BM and referred to the pediatric ward of Abuzar Hospital (Ahvaz, Iran). The samples were monitored by gram stain, cultures, and the PCR method. The patients' age mean was 23 ± 0.56 months. The 196 patients comprised 92 (46.9%) boys and 104 (53.06%) girls. Based on bacterial cultures, just three isolates of H. influenzae were detected. However, PCR detected this bacterium in eight patients. Streptococcus pneumoniae was detected in five (2.5%) patients by the amplification of the lytA gene and in one (0.5%) patient by ply. In this study, no N. meningitidis isolate was in the CSF samples, based on the bacterial culture or PCR results. Streptococcus agalactiae was detected only in one patient, based on PCR. In conclusion, in the present study, the PCR method was more sensitive and rapid than culture for detecting the infectious agents in BM. For this reason, this diagnosis method is recommended for BM. Copyright © 2016. Published by Elsevier Taiwan.

Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis.

PubMed

Sprong, Tom; Brandtzaeg, Petter; Fung, Michael; Pharo, Anne M; Høiby, E Arne; Michaelsen, Terje E; Aase, Audun; van der Meer, Jos W M; van Deuren, Marcel; Mollnes, Tom E

2003-11-15

The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the effect of complement inhibition on inflammation and bacterial killing. Monoclonal antibodies (mAbs) blocking lectin and alternative pathways inhibited complement activation by N meningitidis and oxidative burst induced in granulocytes and monocytes. Oxidative burst was critically dependent on CD11b/CD18 (CR3) expression but not on Fc gamma-receptors. Specific inhibition of C5a using mAb 137-26 binding the C5a moiety of C5 before cleavage prohibited CR3 up-regulation, phagocytosis, and oxidative burst but had no effect on C5b-9 (TCC) formation, lysis, and bacterial killing. An mAb-blocking cleavage of C5, preventing C5a and TCC formation, showed the same effect on CR3, phagocytosis, and oxidative burst as the anti-C5a mAb but additionally inhibited TCC formation, lysis, and bacterial killing, consistent with a C5b-9-dependent killing mechanism. In conclusion, the anti-C5a mAb 137-26 inhibits the potentially harmful effects of N meningitidis-induced C5a formation while preserving complement-mediated bacterial killing. We suggest that this may be an attractive approach for the treatment of meningococcal sepsis.

THE SECOND BLIND SPOT: SMALL RETINAL VESSEL VASCULOPATHY AFTER VACCINATION AGAINST NEISSERIA MENINGITIDIS AND YELLOW FEVER.

PubMed

Moysidis, Stavros N; Koulisis, Nicole; Patel, Vivek R; Kashani, Amir H; Rao, Narsing A; Humayun, Mark S; Rodger, Damien C

2017-01-01

To describe a case of small retinal vessel vasculopathy postvaccination. We report the case of a 41-year-old white man who presented with a "second blind spot," describing a nasal scotoma in the right eye that started 4 days after vaccinations against Neisseria meningitidis and the yellow fever virus, and after a 2-month period of high stress and decreased sleep. Clinical examination, Humphrey visual field testing, and multimodal imaging with fundus photographs, autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography and angiography were performed. Clinical examination revealed a well-circumscribed, triangular area of retinal graying of about 1-disk diameter in size, located at the border of the temporal macula. This corresponded to a deep scotoma similar in size to the physiologic blind spot on Humphrey visual field 24-2 testing. There was mild hypoautofluoresence of this lesion on autofluorescence, hypofluorescence on fluorescein angiography, and focal attenuation of a small artery just distal to the bifurcation of an artery supplying the involved area. Spectral domain optical coherence tomography through the lesion conveyed hyperreflectivity most prominent in the inner and outer plexiform layers, with extension of the hyperreflectivity into the ganglion cell and inner nuclear layers. Spectral domain optical coherence tomography angiography demonstrated arteriolar and capillary dropout, more pronounced in the superficial retinal layer compared to the deeper retinal layer. At 1-month follow-up, his scotoma improved with monitoring, with reduction from -32 dB to -7 dB on Humphrey visual field testing. There was clinical resolution of the area of graying and decreased hyperreflectivity on spectral domain optical coherence tomography, with atrophy of the inner retina. Spectral domain optical coherence tomography angiography showed progression of arteriolar and capillary dropout, more so in the superficial than in the deep capillary plexus. We describe a case of small artery occlusion in a previously healthy patient, 4 days after vaccination against N. meningitidis and yellow fever. Fluorescein angiography yielded greater diagnostic value than OCTA for evaluating the occlusion, whereas spectral domain optical coherence tomography angiography enabled better visualization of capillary dropout and layer-specific assessment. Further research is required to determine whether vaccination in general, or directed specifically at N. meningitidis or yellow fever, is associated with small vessel vasculopathy and the underlying pathogenesis.

Modulation of the biological activities of meningococcal endotoxins by association with outer membrane proteins is not inevitably linked to toxicity.

PubMed Central

Quakyi, E K; Hochstein, H D; Tsai, C M

1997-01-01

Meningococcal sepsis results partly from overproduction of host cytokines after macrophages interact with endotoxin. To obtain less toxic and highly immunomodulatory meningococcal endotoxins for prophylactic purposes, we investigated the relationship between endotoxicity and immunomodulatory activity of several endotoxin preparations from Neisseria meningitidis group B. Using the D-galactosamine-sensitized mouse model to determine endotoxin lethality, we found that the toxicity of purified lipooligosaccharide (LOS) from M986, a group B disease strain, was three to four times higher than those of purified LOSs from the noncapsulated strains M986-NCV-1 and OP-, the truncated-LOS mutant. The LOSs of outer membrane vesicles (OMVs) and detergent-treated OMVs (D-OMVs) from the three strains were 2 to 3 and over 300 times less toxic than the purified LOSs, respectively. Intraperitoneal administration of these preparations induced production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum 2 h after injections. However, repeated doses of low- and high-toxicity preparations induced lower amounts of TNF-alpha and IL-6, i.e., LOS tolerance. Injection of mice with low doses of LOS was as effective as injection with high doses in inducing tolerance. Peritoneal macrophages from tolerant mice pretreated with either high- or low-toxicity LOS preparations produced only a fraction of the amounts of TNF-alpha and IL-6 produced by control groups in response to LOS ex vivo. Despite tolerance to LOS induced by pretreatment with reduced-toxicity preparations, killing of N. meningitidis M986 by macrophages from these animals was enhanced. Protection was achieved when mice treated with LOS, and especially that of D-OMVs, were challenged with live N. meningitidis. The least toxic LOS, that in D-OMVs, was most effective in inducing hyporesponsiveness to endotoxin in mice but protected them against challenge with N. meningitidis. No inevitable link between toxicity and host immune modulation and responses was shown. Our results show that LOS is responsible for both toxicity and immunomodulation. When LOS is tightly associated with outer membrane proteins in D-OMV, it reduces toxicity but enhances beneficial effects compared to results with its purified form. Thus, systematic and critical evaluation of D-OMVs as adjuvants or as portions of group B meningococcal vaccines may help improve survival and outcome in meningococcal sepsis. PMID:9125592

Carriage rates and serogroups of Neisseria meningitidis among freshmen in a University dormitory in Korea.

PubMed

Durey, Areum; Bae, Song-Mee; Lee, Hye-Jin; Nah, So-Yun; Kim, Mijeong; Baek, Ji Hyeon; Kang, Yeon-Ho; Chung, Moon-Hyun; Lee, Jin-Soo

2012-07-01

Neisseria meningitidis is a leading cause of bacterial meningitis in young adults. University students, especially those living in dormitories, have been known to be at increased risk of meningococcal disease. We performed a longitudinal study to determine the carriage rates of N. meningitidis and the changes thereof. We recruited Inha University freshmen who were, at that time, admitted to a student dormitory. A pharyngeal swab was taken from all participant who were also asked to complete a questionnaire. This was repeated four weeks later. A total of 136 students were enrolled at the first culture. After four weeks, 128 students were enrolled, including 106 re-participants. The overall carriage rates changed from 11.8% to 14.1%. In analysis of the 106 re-participants, "visiting to pubs" was associated with carriage of N. meningitis for both the first (p=0.047) and second cultures (p=0.026). Serogroup C was found to be the most frequent serogroup (5 isolates), while 3 isolates were found from serogroup B. The most prevalent PorA types were P1.22,14-6 (4 isolates) and P1.19,15 (3 isolates). The DNA sequences of PorA VR2 were changed in 2 students during prolonged carriage. The meningococcal carriage rate among first year university students who resided in a dormitory did not significantly increase over 4-week interval between cultures, which is markedly different from those reported in Western studies. Close social contact appeared to be related with carriage. Our data also revealed diversity in PorA types, suggesting the possibility of rapid mutation of the PorA gene during the 4-week interval.

Carriage Rates and Serogroups of Neisseria meningitidis among Freshmen in a University Dormitory in Korea

PubMed Central

Durey, Areum; Bae, Song-Mee; Lee, Hye-Jin; Nah, So-Yun; Kim, Mijeong; Baek, Ji Hyeon; Kang, Yeon-Ho; Chung, Moon-Hyun

2012-01-01

Purpose Neisseria meningitidis is a leading cause of bacterial meningitis in young adults. University students, especially those living in dormitories, have been known to be at increased risk of meningococcal disease. We performed a longitudinal study to determine the carriage rates of N. meningitidis and the changes thereof. Materials and Methods We recruited Inha University freshmen who were, at that time, admitted to a student dormitory. A pharyngeal swab was taken from all participant who were also asked to complete a questionnaire. This was repeated four weeks later. Results A total of 136 students were enrolled at the first culture. After four weeks, 128 students were enrolled, including 106 re-participants. The overall carriage rates changed from 11.8% to 14.1%. In analysis of the 106 re-participants, "visiting to pubs" was associated with carriage of N. meningitis for both the first (p=0.047) and second cultures (p=0.026). Serogroup C was found to be the most frequent serogroup (5 isolates), while 3 isolates were found from serogroup B. The most prevalent PorA types were P1.22,14-6 (4 isolates) and P1.19,15 (3 isolates). The DNA sequences of PorA VR2 were changed in 2 students during prolonged carriage. Conclusion The meningococcal carriage rate among first year university students who resided in a dormitory did not significantly increase over 4-week interval between cultures, which is markedly different from those reported in Western studies. Close social contact appeared to be related with carriage. Our data also revealed diversity in PorA types, suggesting the possibility of rapid mutation of the PorA gene during the 4-week interval. PMID:22665340

Large-scale study of the interactions between proteins involved in type IV pilus biology in Neisseria meningitidis: characterization of a subcomplex involved in pilus assembly.

PubMed

Georgiadou, Michaella; Castagnini, Marta; Karimova, Gouzel; Ladant, Daniel; Pelicic, Vladimir

2012-06-01

The functionally versatile type IV pili (Tfp) are one of the most widespread virulence factors in bacteria. However, despite generating much research interest for decades, the molecular mechanisms underpinning the various aspects of Tfp biology remain poorly understood, mainly because of the complexity of the system. In the human pathogen Neisseria meningitidis for example, 23 proteins are dedicated to Tfp biology, 15 of which are essential for pilus biogenesis. One of the important gaps in our knowledge concerns the topology of this multiprotein machinery. Here we have used a bacterial two-hybrid system to identify and quantify the interactions between 11 Pil proteins from N. meningitidis. We identified 20 different binary interactions, many of which are novel. This represents the most complex interaction network between Pil proteins reported to date and indicates, among other things, that PilE, PilM, PilN and PilO, which are involved in pilus assembly, indeed interact. We focused our efforts on this subset of proteins and used a battery of assays to determine the membrane topology of PilN and PilO, map the interaction domains between PilE, PilM, PilN and PilO, and show that a widely conserved N-terminal motif in PilN is essential for both PilM-PilN interactions and pilus assembly. Finally, we show that PilP (another protein involved in pilus assembly) forms a complex with PilM, PilN and PilO. Taken together, these findings have numerous implications for understanding Tfp biology and provide a useful blueprint for future studies. © 2012 Blackwell Publishing Ltd.

Use of restriction fragment length polymorphisms to investigate strain variation within Neisseria meningitidis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, S.D.

1989-01-01

Similarity within bacterial populations is difficult to assess due to the limited number of characters available for evaluation and the heterogeneity of bacterial species. Currently, the preferred method used to evaluate the structure of bacterial populations is multilocus enzyme electrophoresis. However, this method is extremely cumbersome and only offers an indirect measure of genetic similarities. The development of a more direct and less cumbersome method for this purpose is warranted. Restriction fragment length polymorphism analysis was evaluated as a tool for use in the study of bacterial population structures and in the epidemiology and surveillance of infectious disease. A collectionmore » of Neisseria meningitidis was available for use in the investigation of this technique. Neisseria meningitidis is the causative agent of epidemic cerebrospinal meningitis and septicemia as well as a variety of other clinical manifestations. Each isolate in the collection was defined in terms of serogroup specificity, clinical history, geographic source, and date of isolation. Forty-six strains were chosen for this study. The DNA from each strain was restricted with Pst1 and EcoR1 and electrophoresed on agarose gels. The DNA was transferred to nylon filters and hybridized with P{sup 32} labeled DNA probes. Two randomly generated probes and a gene-specific probe were used to estimate the genetic similarities between and among the strains in the study population. A total of 28 different restriction fragment migration types were detected by the probes used. Data obtained from the RFLP analysis was analyzed by cluster analysis and multivariate statistical methods. A total of 7 clones groups were detected. Two of these appear to be major clones that comprise 35% of the population.« less

Factor H-binding protein is important for meningococcal survival in human whole blood and serum and in the presence of the antimicrobial peptide LL-37.

PubMed

Seib, K L; Serruto, D; Oriente, F; Delany, I; Adu-Bobie, J; Veggi, D; Aricò, B; Rappuoli, R; Pizza, M

2009-01-01

Factor H-binding protein (fHBP; GNA1870) is one of the antigens of the recombinant vaccine against serogroup B Neisseria meningitidis, which has been developed using reverse vaccinology and is the basis of a meningococcal B vaccine entering phase III clinical trials. Binding of factor H (fH), an inhibitor of the complement alternative pathway, to fHBP enables N. meningitidis to evade killing by the innate immune system. All fHBP null mutant strains analyzed were sensitive to killing in ex vivo human whole blood and serum models of meningococcal bacteremia with respect to the isogenic wild-type strains. The fHBP mutant strains of MC58 and BZ83 (high fHBP expressors) survived in human blood and serum for less than 60 min (decrease of >2 log(10) CFU), while NZ98/254 (intermediate fHBP expressor) and 67/00 (low fHBP expressor) showed decreases of >1 log(10) CFU after 60 to 120 min of incubation. In addition, fHBP is important for survival in the presence of the antimicrobial peptide LL-37 (decrease of >3 log(10) CFU after 2 h of incubation), most likely due to electrostatic interactions between fHBP and the cationic LL-37 molecule. Hence, the expression of fHBP by N. meningitidis strains is important for survival in human blood and human serum and in the presence of LL-37, even at low levels. The functional significance of fHBP in mediating resistance to the human immune response, in addition to its widespread distribution and its ability to induce bactericidal antibodies, indicates that it is an important component of the serogroup B meningococcal vaccine.

Bacteriocins (meningocins) in Norwegian isolates of Neisseria meningitidis: possible role in the course of a meningococcal epidemic.

PubMed

Allunans, Juris; Kristiansen, Knut Ivan; Assalkhou, Reza; Bjørås, Magnar

2008-05-01

In the Neisseria meningitidis strain MC58 (serogroup B; ET-5 complex) genome three putative islands of horizontally transferred DNA (IHTs) have been identified. IHT-A2 codes for eight hypothetical proteins and two disrupted open reading frames with similarity to a secretion protein (NMB0097) and an ABC transporter (NMB0098). The strains MC58 and 44/76 (shown here) are meningocin resistant/weakly sensitive. None of these strains are meningocin producers. However, NMB0097 and NMB0098 homologues with open reading frames are found in meningocin producers (N. meningitidis P241 (serogroup A; systemic isolate) and BT878 (serogroup B; carrier isolate), and also in strain FAM18 (serogroup C; ET-37 complex). Knocking out either of the two genes in the strain BT878 yielded mutants that did not secrete meningocin. A similarly disrupted tolC mutant in strain BT878 still released meningocin. Among systemic meningococcal isolates prior to and at the onset (mid-1973 to the end of 1974) of the epidemic peaking in 1975 in North Norway, 12 of 30 (40%) isolates of serogroup A were meningocin producers. However, the rate for serogroup B was 1 of 45 (2.2%). Serogroup B meningocin-resistant/weakly sensitive non-producers dominated in the region from mid-1975 and spread to the rest of the country from then on. No producers were found in selected pharyngeal isolates from healthy carriers collected in Svalbard in the early spring of 1975. Our results suggest that meningocinogeny has played a part in the change from serogroup A to serogroup B among isolates in North Norway during the first half of 1975.

Predictors of Meningococcal Vaccination among University Students

ERIC Educational Resources Information Center

D'Heilly, Sarah; Ehlinger, Edward; Nichol, Kristin

2006-01-01

Invasive disease secondary to Neisseria meningitidis is a rare but devastating illness among university students. The Advisory Committee on Immunization Practices recommends educating college freshmen about meningococcal disease and vaccinating all college freshmen who live in residence halls. We conducted this survey to gain a better…

Community-Based Outbreak of Neisseria meningitidis Serogroup C Infection in Men who Have Sex with Men, New York City, New York, USA, 2010−2013

PubMed Central

Weiss, Don; Ridpath, Alison; Zucker, Jane R.; Geevarughese, Anita; Rakeman, Jennifer; Varma, Jay K.

2015-01-01

In September 2012, the New York City Department of Health and Mental Hygiene identified an outbreak of Neisseria meningitidis serogroup C invasive meningococcal disease among men who have sex with men (MSM). Twenty-two case-patients and 7 deaths were identified during August 2010−February 2013. During this period, 7 cases in non-MSM were diagnosed. The slow-moving outbreak was linked to the use of websites and mobile phone applications that connect men with male sexual partners, which complicated the epidemiologic investigation and prevention efforts. We describe the outbreak and steps taken to interrupt transmission, including an innovative and wide-ranging outreach campaign that involved direct, internet-based, and media-based communications; free vaccination events; and engagement of community and government partners. We conclude by discussing the challenges of managing an outbreak affecting a discrete community of MSM and the benefits of using social networking technology to reach this at-risk population. PMID:26197087

Naturally Occurring Off-Switches for CRISPR-Cas9.

PubMed

Pawluk, April; Amrani, Nadia; Zhang, Yan; Garcia, Bianca; Hidalgo-Reyes, Yurima; Lee, Jooyoung; Edraki, Alireza; Shah, Megha; Sontheimer, Erik J; Maxwell, Karen L; Davidson, Alan R

2016-12-15

CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These "anti-CRISPRs" were specific to type I CRISPR-Cas systems that do not employ the Cas9 protein. We posited that nature would also yield Cas9 inhibitors in response to the evolutionary arms race between bacteriophages and their hosts. Here, we report the discovery of three distinct families of anti-CRISPRs that specifically inhibit the CRISPR-Cas9 system of Neisseria meningitidis. We show that these proteins bind directly to N. meningitidis Cas9 (NmeCas9) and can be used as potent inhibitors of genome editing by this system in human cells. These anti-CRISPR proteins now enable "off-switches" for CRISPR-Cas9 activity and provide a genetically encodable means to inhibit CRISPR-Cas9 genome editing in eukaryotes. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure and mechanism of a molecular rheostat, an RNA thermometer that modulates immune evasion by Neisseria meningitidis

PubMed Central

Barnwal, Ravi Pratap; Loh, Edmund; Godin, Katherine S.; Yip, Jordan; Lavender, Hayley; Tang, Christoph M.; Varani, Gabriele

2016-01-01

Neisseria meningitidis causes bacterial meningitis and septicemia. It evades the host complement system by upregulating expression of immune evasion factors in response to changes in temperature. RNA thermometers within mRNAs control expression of bacterial immune evasion factors, including CssA, in the 5′-untranslated region of the operon for capsule biosynthesis. We dissect the molecular mechanisms of thermoregulation and report the structure of the CssA thermometer. We show that the RNA thermometer acts as a rheostat, whose stability is optimized to respond in a small temperature range around 37°C as occur within the upper airways during infection. Small increases in temperature gradually open up the structure to allow progressively increased access to the ribosome binding site. Even small changes in stability induced by mutations of imperfect base pairs, as in naturally occurring polymorphisms, shift the thermometer response outside of the desired temperature range, suggesting that its activity could be modulated by pharmacological intervention. PMID:27369378

Naturally occurring off-switches for CRISPR-Cas9

PubMed Central

Pawluk, April; Amrani, Nadia; Zhang, Yan; Garcia, Bianca; Hidalgo-Reyes, Yurima; Lee, Jooyoung; Edraki, Alireza; Shah, Megha; Sontheimer, Erik J.; Maxwell, Karen L.; Davidson, Alan R.

2017-01-01

Summary CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These “anti-CRISPRs” were specific to type I CRISPR-Cas systems that do not employ the Cas9 protein. We posited that nature would also yield Cas9 inhibitors in response to the evolutionary arms race between bacteriophages and their hosts. Here, we report the discovery of three distinct families of anti-CRISPRs that specifically inhibit the CRISPR-Cas9 system of Neisseria meningitidis. We show that these proteins bind directly to N. meningitidis Cas9 (NmeCas9), and can be used as potent inhibitors of genome editing by this system in human cells. These anti-CRISPR proteins now enable “off-switches” for CRISPR-Cas9 activity, and provide a genetically-encodable means to inhibit CRISPR-Cas9 genome editing in eukaryotes. PMID:27984730

Trend of bacterial meningitis in Bahrain from 1990 to 2013 and effect of introduction of new vaccines.

PubMed

Saeed, N; AlAnsari, H; AlKhawaja, S; Jawad, J S; Nasser, K; AlYousef, E

2016-06-15

Meningitis is among the 10 commonest infectious causes of death worldwide. This retrospective analysis of reported cases of meningitis in Bahrain aimed to assess the trend in the incidence of bacterial meningitis from 1990 to 2013, before and after the introduction of new vaccines. Of 1455 reported cases of meningitis during the study period 73.1% were viral and 26.9% were bacterial etiology (tuberculous meningitis 8.3%; Streptococcus pneumoniae 4.9%, Haemophilus influenzae 3.6% and Neisseria meningitidis 1.7%). There was a peak of meningitis cases in 1995-1996. The incidence of meningitis due to H. influenzae and N. meningitidis showed a marked reduction after the introduction of the corresponding vaccines in 1998 and 2001 respectively, and S. pneumoniae became the predominant organism after Mycobacterium tuberculosis. The changing trend in the etiology of bacterial meningitis points to the need to study vaccination programme modifications, such as pneumococcal vaccine for the adult population, especially high-risk groups.

Whole-Genome Characterization of Epidemic Neisseria meningitidis Serogroup C and Resurgence of Serogroup W, Niger, 2015.

PubMed

Kretz, Cecilia B; Retchless, Adam C; Sidikou, Fati; Issaka, Bassira; Ousmane, Sani; Schwartz, Stephanie; Tate, Ashley H; Pana, Assimawè; Njanpop-Lafourcade, Berthe-Marie; Nzeyimana, Innocent; Nse, Ricardo Obama; Deghmane, Ala-Eddine; Hong, Eva; Brynildsrud, Ola Brønstad; Novak, Ryan T; Meyer, Sarah A; Oukem-Boyer, Odile Ouwe Missi; Ronveaux, Olivier; Caugant, Dominique A; Taha, Muhamed-Kheir; Wang, Xin

2016-10-01

In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC epidemic coincided with serogroup W (NmW) cases during the epidemic season, resulting in a total of 9,367 meningococcal cases through June 2015. To clarify the phylogenetic association, genetic evolution, and antibiotic determinants of the meningococcal strains in Niger, we sequenced the genomes of 102 isolates from this epidemic, comprising 81 NmC and 21 NmW isolates. The genomes of 82 isolates were completed, and all 102 were included in the analysis. All NmC isolates had sequence type 10217, which caused the outbreaks in Nigeria during 2013-2014 and for which a clonal complex has not yet been defined. The NmC isolates from Niger were substantially different from other NmC isolates collected globally. All NmW isolates belonged to clonal complex 11 and were closely related to the isolates causing recent outbreaks in Africa.

Mobile DNA in the pathogenic Neisseria

PubMed Central

Obergfell, Kyle P.; Seifert, H. Steven

2015-01-01

The genus Neisseria contains two pathogenic species of notable public health concern: Neisseria gonorrhoeae and Neisseria meningitidis. These pathogens display a notable ability to undergo frequent programmed recombination events. The recombination mediated pathways of transformation and pilin antigenic variation in the Neisseria are well studied systems that are critical for pathogenesis. Here we will detail the conserved and unique aspects of transformation and antigenic variation in the Neisseria. Transformation will be followed from initial DNA binding through recombination into the genome with consideration to the factors necessary at each step. Additional focus is paid to the unique type IV secretion system that mediates donation of transforming DNA in the pathogenic Neisseria. The pilin antigenic variation system uses programed recombinations to alter a major surface determinant which allows immune avoidance and promotes infection. We discuss the trans- and cis- acting factors which facilitate pilin antigenic variation and present the current understanding of the mechanisms involved in the process. PMID:25866700

Serological Analysis of Immunogenic Properties of Recombinant Meningococcus IgA1 Protease-Based Proteins.

PubMed

Kotelnikova, O V; Zinchenko, A A; Vikhrov, A A; Alliluev, A P; Serova, O V; Gordeeva, E A; Zhigis, L S; Zueva, V S; Razgulyaeva, O A; Melikhova, T D; Nokel, E A; Drozhzhina, E Yu; Rumsh, L D

2016-07-01

Using the genome sequence of IgA1 protease of N. meningitidis of serogroup B, four recombinant proteins of different structure and molecular weight were constructed. These proteins were equal in inducing the formation of specific antibodies to IgA1 protease and had protective properties against meningococci. In the sera of immunized mice, anti-IgA1 protease antibodies were detected by whole-cell ELISA, which indicated the presence of IgA1 protease on the surface of these bacteria. We hypothesized that the protective properties of IgA1 protease-based antigens and IgA1 protease analogs could be realized not only via impairment of bacterium adhesion to the mucosa, but also via suppression of this pathogen in the organism. The presented findings seem promising for using these proteins as the basis for anti-meningococcus vaccine.

New Meningococcal Vaccine Recommendations under Consideration

ERIC Educational Resources Information Center

Turner, James C.

2004-01-01

The Advisory Committee on Immunization Practices (ACIP) at the Center for Disease Control and Prevention (CDC) will be considering a new vaccination recommendation for the prevention of invasive "N. meningitidis" infection when meningococcal conjugate vaccines are licensed in the United States. The CDC has also updated the Working Group…

Structural and functional features of a developmentally regulated lipopolysaccharide-binding protein.

PubMed

Krasity, Benjamin C; Troll, Joshua V; Lehnert, Erik M; Hackett, Kathleen T; Dillard, Joseph P; Apicella, Michael A; Goldman, William E; Weiss, Jerrold P; McFall-Ngai, Margaret J

2015-10-13

Mammalian lipopolysaccharide (LPS) binding proteins (LBPs) occur mainly in extracellular fluids and promote LPS delivery to specific host cell receptors. The function of LBPs has been studied principally in the context of host defense; the possible role of LBPs in nonpathogenic host-microbe interactions has not been well characterized. Using the Euprymna scolopes-Vibrio fischeri model, we analyzed the structure and function of an LBP family protein, E. scolopes LBP1 (EsLBP1), and provide evidence for its role in triggering a symbiont-induced host developmental program. Previous studies showed that, during initial host colonization, the LPS of V. fischeri synergizes with peptidoglycan (PGN) monomer to induce morphogenesis of epithelial tissues of the host animal. Computationally modeled EsLBP1 shares some but not all structural features of mammalian LBPs that are thought important for LPS binding. Similar to human LBP, recombinant EsLBP1 expressed in insect cells bound V. fischeri LPS and Neisseria meningitidis lipooligosaccharide (LOS) with nanomolar or greater affinity but bound Francisella tularensis LPS only weakly and did not bind PGN monomer. Unlike human LBP, EsLBP1 did not bind N. meningitidis LOS:CD14 complexes. The eslbp1 transcript was upregulated ~22-fold by V. fischeri at 24 h postinoculation. Surprisingly, this upregulation was not induced by exposure to LPS but, rather, to the PGN monomer alone. Hybridization chain reaction-fluorescent in situ hybridization (HCR-FISH) and immunocytochemistry (ICC) localized eslbp1 transcript and protein in crypt epithelia, where V. fischeri induces morphogenesis. The data presented here provide a window into the evolution of LBPs and the scope of their roles in animal symbioses. Mammalian lipopolysaccharide (LPS)-binding protein (LBP) is implicated in conveying LPS to host cells and potentiating its signaling activity. In certain disease states, such as obesity, the overproduction of this protein has been a reliable biomarker of chronic inflammation. Here, we describe a symbiosis-induced invertebrate LBP whose tertiary structure and LPS-binding characteristics are similar to those of mammalian LBPs; however, the primary structure of this distantly related squid protein (EsLBP1) differs in key residues previously believed to be essential for LPS binding, suggesting that an alternative strategy exists. Surprisingly, symbiotic expression of eslbp1 is induced by peptidoglycan derivatives, not LPS, a pattern converse to that of RegIIIγ, an important mammalian immunity protein that binds peptidoglycan but whose gene expression is induced by LPS. Finally, EsLBP1 occurs along the apical surfaces of all the host's epithelia, suggesting that it was recruited from a general defensive role to one that mediates specific interactions with its symbiont. Copyright © 2015 Krasity et al.

Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens

PubMed Central

Cywes-Bentley, Colette; Skurnik, David; Zaidi, Tanweer; Roux, Damien; DeOliveira, Rosane B.; Garrett, Wendy S.; Lu, Xi; O’Malley, Jennifer; Kinzel, Kathryn; Zaidi, Tauqeer; Rey, Astrid; Perrin, Christophe; Fichorova, Raina N.; Kayatani, Alexander K. K.; Maira-Litràn, Tomas; Gening, Marina L.; Tsvetkov, Yury E.; Nifantiev, Nikolay E.; Bakaletz, Lauren O.; Pelton, Stephen I.; Golenbock, Douglas T.; Pier, Gerald B.

2013-01-01

Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)–linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology. PMID:23716675

Meningococcal ACWY Vaccines - MenACWY and MPSV4: What You Need to Know

MedlinePlus

... Infants younger than one year old • Adolescents and young adults 16 through 23 years old • People with certain medical conditions that affect the immune system • Microbiologists who routinely work with isolates of N. meningitidis • People at risk because of an outbreak in their community Even ...

Rapid Detection of Bacterial Antibiotic Resistance: Preliminary Evaluation of PCR Assays Targeting Tetracycline Resistance Genes

DTIC Science & Technology

2007-08-01

gonorrheae strain 2309 plasmid pOZ101; AF440277, Lactobacillus plantarum plasmid pMD5057; X75073, Neisseria meningitidis plasmid DNA for tet(M...tetracycline resistance tet(M) gene; AY057892, Staphylococcus aureus strain 1802 tetracycline resistance protein tet(M) gene; AY149596, Lactobacillus sakei

Into Darkness and Silence: What Caused Helen Keller's Deafblindness?

PubMed

Gilsdorf, Janet R

2018-05-05

In 1882, at 19 months of age, Helen Keller developed a febrile illness that left her both deaf and blind. Historical biographies attribute the illness to rubella, scarlet fever, encephalitis, or meningitis. This analysis of her illness suggests she likely had bacterial meningitis, caused by N. meningitidis or possibly H. influenzae.

Penicillin resistance compromises Nod1-dependent proinflammatory activity and virulence fitness of neisseria meningitidis.

PubMed

Zarantonelli, Maria Leticia; Skoczynska, Anna; Antignac, Aude; El Ghachi, Meriem; Deghmane, Ala-Eddine; Szatanik, Marek; Mulet, Céline; Werts, Catherine; Peduto, Lucie; d'Andon, Martine Fanton; Thouron, Françoise; Nato, Faridabano; Lebourhis, Lionel; Philpott, Dana J; Girardin, Stephen E; Vives, Francina Langa; Sansonetti, Philippe; Eberl, Gérard; Pedron, Thierry; Taha, Muhamed-Kheir; Boneca, Ivo G

2013-06-12

Neisseria meningitidis is a life-threatening human bacterial pathogen responsible for pneumonia, sepsis, and meningitis. Meningococcal strains with reduced susceptibility to penicillin G (Pen(I)) carry a mutated penicillin-binding protein (PBP2) resulting in a modified peptidoglycan structure. Despite their antibiotic resistance, Pen(I) strains have failed to expand clonally. We analyzed the biological consequences of PBP2 alteration among clinical meningococcal strains and found that peptidoglycan modifications of the Pen(I) strain resulted in diminished in vitro Nod1-dependent proinflammatory activity. In an influenza virus-meningococcal sequential mouse model mimicking human disease, wild-type meningococci induced a Nod1-dependent inflammatory response, colonizing the lungs and surviving in the blood. In contrast, isogenic Pen(I) strains were attenuated for such response and were out-competed by meningococci sensitive to penicillin G. Our results suggest that antibiotic resistance imposes a cost to the success of the pathogen and may potentially explain the lack of clonal expansion of Pen(I) strains. Copyright © 2013 Elsevier Inc. All rights reserved.

Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4

PubMed Central

Maïssa, Nawal; Covarelli, Valentina; Janel, Sébastien; Durel, Beatrice; Simpson, Nandi; Bernard, Sandra C.; Pardo-Lopez, Liliana; Bouzinba-Ségard, Haniaa; Faure, Camille; Scott, Mark G.H.; Coureuil, Mathieu; Morand, Philippe C.; Lafont, Frank; Nassif, Xavier; Marullo, Stefano; Bourdoulous, Sandrine

2017-01-01

Neisseria meningitidis (meningococcus) is an invasive bacterial pathogen that colonizes human vessels, causing thrombotic lesions and meningitis. Establishment of tight interactions with endothelial cells is crucial for meningococci to resist haemodynamic forces. Two endothelial receptors, CD147 and the β2-adrenergic receptor (β2AR), are sequentially engaged by meningococci to adhere and promote signalling events leading to vascular colonization, but their spatiotemporal coordination is unknown. Here we report that CD147 and β2AR form constitutive hetero-oligomeric complexes. The scaffolding protein α-actinin-4 directly binds to the cytosolic tail of CD147 and governs the assembly of CD147–β2AR complexes in highly ordered clusters at bacterial adhesion sites. This multimolecular assembly process increases the binding strength of meningococci to endothelial cells under shear stress, and creates molecular platforms for the elongation of membrane protrusions surrounding adherent bacteria. Thus, the specific organization of cellular receptors has major impacts on host–pathogen interaction. PMID:28569760

Surveillance of bacterial meningitis in the country of Georgia, 2006-2010.

PubMed

Butsashvili, Maia; Kandelaki, George; Eloshvili, Medea; Chlikadze, Rusudan; Imnadze, Paata; Avaliani, Nata

2013-08-01

Bacterial meningitis remains important cause of morbidity and mortality worldwide, particularly in developing countries. This study analyzed the data from sentinel surveillance for bacterial meningitis among children <5 years of age hospitalized in largest children's hospital in Tbilisi, capital of Georgia and adult patients hospitalized in infectious diseases hospital during 2006-2010 with suspected bacterial meningitis. The surveillance is conducted by National Center for Disease Control and Public Health (NCDCPH). The number of patients with identified organism was 127 (19 %). In the subsample of patients with laboratory confirmed bacterial meningitis Streptococcus pneumoniae was the most frequently isolated organism (67 cases, 52.8 %), followed by. influenza (17 cases, 13.4 %) and Neisseria meningitidis (16 cases, 12.6 %). The number of patients with suspected TB meningitis was 27 (21.3 %). The overall case fatality rate in the subgroup of patients with identified organism was 12.3 %. The highest mortality was observed among TB patients (22.2 %) with 14.3 % mortality for N. meningitidis and 10.3 % for S. pneumoniae. No lethal outcome was observed among patients with Haemophilus influenzae.

How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines

PubMed Central

Gasparini, R.; Panatto, D.; Bragazzi, N. L.; Lai, P. L.; Bechini, A.; Levi, M.; Durando, P.; Amicizia, D.

2015-01-01

In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity of Neisseria meningitidis at a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics). Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in particular, play a major role in circumventing immune response. The understanding of these mechanisms has opened new horizons in the field of vaccinology. Nowadays different licensed meningococcal vaccines are available and used: conjugate meningococcal C vaccines, tetravalent conjugate vaccines, an affordable conjugate vaccine against the N. menigitidis serogroup A, and universal vaccines based on multiple antigens each one with a different and peculiar function against meningococcal group B strains. PMID:26351643

Detection of Neisseria meningitidis in cerebrospinal fluid using a multiplex PCR and the Luminex detection technology.

PubMed

Møller, Jens Kjølseth

2012-01-01

Rapid clinical and laboratory diagnoses are the foundation for a successful management of serious infections with Neisseria meningitidis. A species-specific multiplex polymerase chain reaction (PCR) coupled with fluidic microarrays using microbeads (the Luminex xMAP™ Technology) can detect pathogens most frequently found in the cerebrospinal fluid of patients. The Luminex suspension array system uniquely combines flow cytometry, microspheres, laser technology, digital signal processing, and traditional chemistry. In this method, the reaction is carried out in one vessel, in which distinctly color-coded bead sets, each conjugated with a different specific nucleic acid reactant, are hybridized with the PCR products, and a reporter molecule is used to quantify the interaction. The flow-based Luminex array reader identifies each reaction (bead set) after excitation by a red classification laser. Reporter signals from each reaction are simultaneously quantified by fluorescence generated by a green reporter laser. This nonculture, multiplex assay may prove to be an important tool for optimal laboratory diagnosis, not only of meningococcal meningitis, but also of meningitis caused by other bacterial or viral pathogens.

Programmable RNA Cleavage and Recognition by a Natural CRISPR-Cas9 System from Neisseria meningitidis.

PubMed

Rousseau, Beth A; Hou, Zhonggang; Gramelspacher, Max J; Zhang, Yan

2018-03-01

The microbial CRISPR systems enable adaptive defense against mobile elements and also provide formidable tools for genome engineering. The Cas9 proteins are type II CRISPR-associated, RNA-guided DNA endonucleases that identify double-stranded DNA targets by sequence complementarity and protospacer adjacent motif (PAM) recognition. Here we report that the type II-C CRISPR-Cas9 from Neisseria meningitidis (Nme) is capable of programmable, RNA-guided, site-specific cleavage and recognition of single-stranded RNA targets and that this ribonuclease activity is independent of the PAM sequence. We define the mechanistic feature and specificity constraint for RNA cleavage by NmeCas9 and also show that nuclease null dNmeCas9 binds to RNA target complementary to CRISPR RNA. Finally, we demonstrate that NmeCas9-catalyzed RNA cleavage can be blocked by three families of type II-C anti-CRISPR proteins. These results fundamentally expand the targeting capacities of CRISPR-Cas9 and highlight the potential utility of NmeCas9 as a single platform to target both RNA and DNA. Copyright © 2018 Elsevier Inc. All rights reserved.

Epidemiological profile of invasive bacterial diseases in children in Casablanca, Morocco: antimicrobial susceptibilities and serotype distribution.

PubMed

El Mdaghri, N; Jilali, N; Belabbes, H; Jouhadi, Z; Lahssoune, M; Zaid, S

2012-11-01

The aim of this prospective study in Morocco was to investigate the causes of invasive bacterial diseases in children in order to inform antibiotic therapy and vaccine choices. Of 238 children aged < or = 5 years admitted to the Children's Hospital of Casablanca for invasive diseases over a 12-month period, 185 were diagnosed with bacterial infection: 76 had chest-X-ray-confirmed pneumonia, 59 had meningitis and 50 had sepsis. Streptococcus pneumoniae was the most common pathogen identified (n = 24), followed by Neisseria meningitidis (n = 18, all group B) and Haemophilus influenzae (n = 11). The rate of penicillin non-susceptibility was 62.5% among Str. pneumoniae isolates and 11.1% among N. meningitidis and all isolates were ceftriaxone-susceptible. Of the 11 H. influenzae isolates, only 1 produced a beta-lactamase. The 5 predominant Str. pneumoniae serotypes were 19F, 14, 23F, 6B and 19A and the theoretical coverage of the 7, 10 and 13-valent pneumococcal conjugate vaccines was 60%, 78% and 91% respectively.

[In vitro activity of doripenem against strains from pediatric diseases and strains causing purulent meningitis].

PubMed

Ohta, Merime; Toba, Shinsuke; Ito, Akinobu; Nakamura, Rio; Tsuji, Masakatsu

2012-12-01

This study evaluated the in vitro activity of doripenem (DRPM) against 200 Streptococcus pneumoniae and 197 Haemophilus influenzae from children and adults in 2007, 50 H. influenzae type b in 2006, 20 Listeria monocytogenes in 1990-2005, 23 Neisseria meningitidis in 2007-2009 and 83 Bordetella pertussis in 1989-2003. All strains were isolated from Japanese clinical facilities. We also investigated in vitro activity of other carbapenems (meropenem, imipenem, panipenem, biapenem), cephems (ceftriaxone, cefotaxime), ampicillin and clarithromycin. The all MICs were determined by a broth micro dilution method or an agar dilution method according to CLSI. The MIC90(s) of DRPM against S. pneumoniae and H. influenzae from children were 0.25 microg/mL, 1 microg/mL, respectively, which were similar to strains from adults. These results suggested that antibacterial activity of DRPM is not variable by patient's age. DRPM also showed excellent activities against H. influenzae type b, L. monocytogenes and N. meningitidis, which cause purulent meningitis, and B. pertussis causing whooping cough more than the other carbapenems. DRPM showed superior activities against serious strains of pediatric infection diseases.

Development of internally controlled duplex real-time NASBA diagnostics assays for the detection of microorganisms associated with bacterial meningitis.

PubMed

Clancy, Eoin; Coughlan, Helena; Higgins, Owen; Boo, Teck Wee; Cormican, Martin; Barrett, Louise; Smith, Terry J; Reddington, Kate; Barry, Thomas

2016-08-01

Three duplex molecular beacon based real-time Nucleic Acid Sequence Based Amplification (NASBA) assays have been designed and experimentally validated targeting RNA transcripts for the detection and identification of Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae respectively. Each real-time NASBA diagnostics assay includes an endogenous non-competitive Internal Amplification Control (IAC) to amplify the splice variant 1 mRNA of the Homo sapiens TBP gene from human total RNA. All three duplex real-time NASBA diagnostics assays were determined to be 100% specific for the target species tested for. Also the Limits of Detection (LODs) for the H. influenzae, N. meningitidis and S. pneumoniae duplex real-time NASBA assays were 55.36, 0.99, and 57.24 Cell Equivalents (CE) respectively. These robust duplex real-time NASBA diagnostics assays have the potential to be used in a clinical setting for the rapid (<60min) specific detection and identification of the most prominent microorganisms associated with bacterial meningitis in humans. Copyright © 2016 Elsevier B.V. All rights reserved.

A comparison of the endotoxin biosynthesis and protein oxidation pathways in the biogenesis of the outer membrane of Escherichia coli and Neisseria meningitidis

PubMed Central

Piek, Susannah; Kahler, Charlene M.

2012-01-01

The Gram-negative bacterial cell envelope consists of an inner membrane (IM) that surrounds the cytoplasm and an asymmetrical outer-membrane (OM) that forms a protective barrier to the external environment. The OM consists of lipopolysaccahride (LPS), phospholipids, outer membrane proteins (OMPs), and lipoproteins. Oxidative protein folding mediated by periplasmic oxidoreductases is required for the biogenesis of the protein components, mainly constituents of virulence determinants such as pili, flagella, and toxins, of the Gram-negative OM. Recently, periplasmic oxidoreductases have been implicated in LPS biogenesis of Escherichia coli and Neisseria meningitidis. Differences in OM biogenesis, in particular the transport pathways for endotoxin to the OM, the composition and role of the protein oxidation, and isomerization pathways and the regulatory networks that control them have been found in these two Gram-negative species suggesting that although form and function of the OM is conserved, the pathways required for the biosynthesis of the OM and the regulatory circuits that control them have evolved to suit the lifestyle of each organism. PMID:23267440

A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria.

PubMed

Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P

2015-09-01

Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. © FASEB.

Does granulocyte colony-stimulating factor ameliorate the proinflammatory response in human meningococcal septic shock?

PubMed

Rojahn, Astrid; Brusletto, Berit; Øvstebø, Reidun; Haug, Kari B F; Kierulf, Peter; Brandtzaeg, Petter

2008-09-01

To test the hypothesis that granulocyte colony-stimulating factor acts cooperatively with interleukin-10 in down-regulating monocyte function in severe meningococcal septic shock. 1) We quantified the plasma levels of granulocyte colony-stimulating factor, interleukin-10, Neisseria meningitidis lipopolysaccharide and the number of N. meningitidis DNA copies in 28 patients with systemic meningococcal disease. 2) We studied the inhibitory effect of recombinant human granulocyte colony-stimulating factor on normal human monocytes stimulated with purified meningococcal lipopolysaccaride. 3) We monitored the inhibitory effects of endogenously produced granulocyte colony-stimulating factor and interleukin-10 in meningococcal shock plasmas on monocytes. Comparative, experimental study. University Hospital and laboratory. Twenty-eight patients with systemic meningococcal disease, 13 with persistent shock, 7 died, and 15 without shock. The median levels of granulocyte colony-stimulating factor in shock and nonshock patients were 1.7 x 10(6) and 8.1 x 10(2) pg/mL; interleukin-10, 2.1 x 10(4) and 4 x 10(1) pg/mL; number of N. meningitidis DNA copies, 2.9 x 10(7) and <10(3)/mL; and lipopolysaccharide, 105 and <0.04 endotoxin units/mL, respectively. The plasma levels of granulocyte colony-stimulating factor were reduced by 50% within 4 to 6 hrs after initiation of antibiotic treatment. In model experiments with lipopolysaccharide-stimulated human monocytes, recombinant human granulocyte colony-stimulating factor and interleukin-10 reduced the release of tumor necrosis factor-alpha by mean 30% and 92%, respectively. When plasmas from three shock patients were depleted of native granulocyte colony-stimulating factor or interleukin-10 by immunoprecipitation, no increase in tumor necrosis factor-alpha release occurred after removal of granulocyte colony-stimulating factor, whereas removal of interleukin-10 increased the tumor necrosis factor-alpha release eight-fold. Although granulocyte colony-stimulating factor in plasma increases by five orders of magnitude in patients with meningococcal shock, the anti-inflammatory effect on patients' monocytes is uncertain.

Atmospheric pressure resistive barrier air plasma jet induced bacterial inactivation in aqueous environment

NASA Astrophysics Data System (ADS)

Thiyagarajan, Magesh; Sarani, Abdollah; Gonzales, Xavier

2013-03-01

An atmospheric pressure resistive barrier air plasma jet is designed to inactivate bacteria in aqueous media in direct and indirect exposure modes of treatment. The resistive barrier plasma jet is designed to operate at both dc and standard 50-60 Hz low frequency ac power input and the ambient air at 50% humidity level was used as the operating gas. The voltage-current characteristics of the plasma jet were analyzed and the operating frequency of the discharge was measured to be 20 kHz and the plasma power was measured to be 26 W. The plasma jet rotational temperatures (Trot) are obtained from the optical emission spectra, from the N2C-B(2+) transitions by matching the experimental spectrum results with the Spectra Air (SPECAIR) simulation spectra. The reactive oxygen and nitrogen species were measured using optical emission spectroscopy and gas analyzers, for direct and indirect treatment modes. The nitric oxides (NO) were observed to be the predominant long lived reactive nitrogen species produced by the plasma. Three different bacteria including Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative), and Neisseria meningitidis (Gram-negative) were suspended in an aqueous media and treated by the resistive barrier air plasma jet in direct and indirect exposure modes. The results show that a near complete bacterial inactivation was achieved within 120 s for both direct and indirect plasma treatment of S. aureus and E. coli bacteria. Conversely, a partial inactivation of N. meningitidis was observed by 120 s direct plasma exposure and insignificant inactivation was observed for the indirect plasma exposure treatment. Plasma induced shifts in N. meningitidis gene expression was analyzed using pilC gene expression as a representative gene and the results showed a reduction in the expression of the pilC gene compared to untreated samples suggesting that the observed protection against NO may be regulated by other genes.

Outer membrane vesicles extracted from Neisseria meningitidis serogroup X for prevention of meningococcal disease in Africa.

PubMed

Acevedo, Reinaldo; Zayas, Caridad; Norheim, Gunnstein; Fernández, Sonsire; Cedré, Barbara; Aranguren, Yisabel; Cuello, Maribel; Rodriguez, Yaimara; González, Humberto; Mandiarote, Aleida; Pérez, Marylin; Hernández, Maritza; Hernández-Cedeño, Mabel; González, Domingo; Brorson, Sverre-Henning; Rosenqvist, Einar; Naess, Lisbeth; Tunheim, Gro; Cardoso, Daniel; García, Luis

2017-07-01

Meningococcal disease is caused mainly by serogroups A, B, C, Y, W of N. meningitidis. However, numerous cases of meningitis caused by serogroup X N. meningitidis (MenX) have recently been reported in several African countries. Currently, there are no licensed vaccines against this pathogen and most of the MenX cases have been caused by meningococci from clonal complex (c.c) 181. Detergent extracted meningococcal outer membrane vesicle (dOMV) vaccines have previously shown to be safe and effective against epidemics of serogroup B meningococcal disease in all age groups. The aim of this work is therefore to obtain, characterize and evaluate the vaccine potential of dOMVs derived from a MenX strain (OMVx). Three experimental lots of OMVx were prepared by deoxycholate extraction from the MenX strain BF 2/97. Size and morphology of the vesicles was determined by Dynamic Light Scattering and electron microscopy, whereas the antigenic composition was characterized by gel electrophoresis and immunoblotting. OMVx were thereafter adsorbed to aluminium hydroxide (OMVx/AL) and two doses of OMVx were administered s.c. to groups of Balb/c mice three weeks apart. The immunogenicity and functional antibody activities in sera were evaluated by ELISA (anti-OMVx specific IgG responses) and serum bactericidal activity (SBA) assay. The size range of OMVx was shown to be between 90 and 120nm, whereas some of the antigens detected were the outer membrane proteins PorA, OpcA and RmpM. The OMVx/AL elicited high anti-OMVx antibody responses with bactericidal activity and no bactericidal activity was observed in the control group of no immunised mice. The results demonstrate that OMVx are immunogenic and could form part of a future vaccine to prevent the majority of meningococcal disease in the African meningitis belt. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of Neisseria meningitidis Isolates from Recent Outbreaks in Ethiopia and Comparison with Those Recovered during the Epidemic of 1988 to 1989

PubMed Central

Norheim, Gunnstein; Rosenqvist, Einar; Aseffa, Abraham; Yassin, Mohammed Ahmed; Mengistu, Getahun; Kassu, Afework; Fikremariam, Dereje; Tamire, Wegene; Høiby, E. Arne; Alebel, Tsegaye; Berhanu, Degu; Merid, Yarid; Harboe, Morten; Caugant, Dominique A.

2006-01-01

The objectives of this study were to collect and characterize epidemic meningococcal isolates from Ethiopia from 2002 to 2003 and to compare them to 21 strains recovered during the previous large epidemic of 1988 to 1989. Ninety-five patients in all age groups with clinical signs of meningitis and a turbid cerebrospinal fluid (CSF) sample were included in the study of isolates from 2002 to 2003. Seventy-one patients (74.7%) were confirmed as having Neisseria meningitidis either by culture (n = 40) or by porA PCR (n = 31) of their CSF. The overall case fatality rate (CFR) was 11.6%; the N. meningitidis-specific CFR was 4.2%. All 40 strains were fully susceptible to all antibiotics tested except sulfonamide, were serotyped as A:4/21:P1.20,9, and belonged to sequence type 7 (ST-7). The strains from 1988 to 1989 were also equally susceptible and were characterized as A:4/21:P1.20,9, but they belonged to ST-5. Antigenic characterization of the strains revealed differences in the repertoire of lipooligosaccharides and Opa proteins between the old and the recent strains. PCR analysis of the nine lgt genes revealed the presence of the lgtAHFG genes in both old and recent strains; lgtB was present in only some of the strains, but no correlation with sequence type was observed. Further analysis showed that in addition to their pgm alleles, the Ethiopian ST-5 and ST-7 strains also differed in their tbpB, opa, fetA, and lgtA genes. The occurrence of new antigenic structures in strains sharing the same serogroup, PorA, and PorB may help explain the replacement of ST-5 by ST-7 in the African meningitis belt. PMID:16517868

Comparison of PCR-based methods for the simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in clinical samples.

PubMed

de Filippis, Ivano; de Andrade, Claudia Ferreira; Caldeira, Nathalia; de Azevedo, Aline Carvalho; de Almeida, Antonio Eugenio

2016-01-01

Several in-house PCR-based assays have been described for the detection of bacterial meningitis caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from clinical samples. PCR-based methods targeting different bacterial genes are frequently used by different laboratories worldwide, but no standard method has ever been established. The aim of our study was to compare different in-house and a commercial PCR-based tests for the detection of bacterial pathogens causing meningitis and invasive disease in humans. A total of 110 isolates and 134 clinical samples (99 cerebrospinal fluid and 35 blood samples) collected from suspected cases of invasive disease were analyzed. Specific sets of primers frequently used for PCR-diagnosis of the three pathogens were used and compared with the results achieved using the multiplex approach described here. Several different gene targets were used for each microorganism, namely ctrA, crgA and nspA for N. meningitidis, ply for S. pneumoniae, P6 and bexA for H. influenzae. All used methods were fast, specific and sensitive, while some of the targets used for the in-house PCR assay detected lower concentrations of genomic DNA than the commercial method. An additional PCR reaction is described for the differentiation of capsulated and non-capsulated H. influenzae strains, the while commercial method only detects capsulated strains. The in-house PCR methods here compared showed to be rapid, sensitive, highly specific, and cheaper than commercial methods. The in-house PCR methods could be easily adopted by public laboratories of developing countries for diagnostic purposes. The best results were achieved using primers targeting the genes nspA, ply, and P6 which were able to detect the lowest DNA concentrations for each specific target. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Immunogenicity and safety of an investigational combined haemophilus influenzae type B-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine.

PubMed

Nolan, Terry; Richmond, Peter; Marshall, Helen; McVernon, Jodie; Alexander, Karyn; Mesaros, Narcisa; Aris, Emmanuel; Miller, Jacqueline; Poolman, Jan; Boutriau, Dominique

2011-03-01

Neisseria meningitidis serogroups B, C, and Y cause most meningococcal disease in industrialized countries. A Haemophilus influenzae type b-meningococcal serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) was evaluated. A total of 1104 infants (randomized 3:1:1) were vaccinated at 2, 4, and 6 months with HibMenCY-TT, MenC-CRM197 + Hib-TT, or Hib-TT. At 12 to 15 months, HibMenCY-TT and MenC-CRM-primed children received HibMenCY-TT; Hib-TT-primed received N. meningitidis serogroup B Hib-outer membrane protein complex. Antibody concentrations and rabbit/human complement serum bactericidal antibody titers (rSBA/hSBA) were determined. Safety was monitored after each dose (diary cards for first 31 days) until 6 months postdose 4. Postdose 3, rates of antipolyribosylribitol phosphate ≥ 1 μg/mL and rSBA-MenC ≥1:128 in HibMenCY-TT recipients were noninferior to licensed controls. Percentages reaching 0.15 μg/mL (1.0 μg/mL postdose 3) and antipolyribosylribitol phosphate GMC were significantly higher after HibMenCY-TT than Hib-TT postdose 2 and postdose 3. The GMC remained significantly higher before and after dose 4. Proportions of HibMenCY-TT recipients with rSBA ≥ 1:8 were 95.6% (MenC), 98.6% (MenY) postdose-2, ≥ 99% for MenC/Y postdose 3 and 4; hSBA ≥ 1:4 were 95.5% (MenC), 89.8% (MenY) postdose 2, >97% for MenC/Y postdose 3 and 4. HibMenCY-TT had a similar safety profile to control vaccines. HibMenCY-TT induced noninferior Hib and MenC responses compared with monovalent Hib and MenC conjugates with a comparable safety profile. Bactericidal antibodies against MenC/Y were induced after 2 doses of HibMenCY-TT.

Bacterial meningitis in Finland, 1995–2014: a population-based observational study

PubMed Central

Polkowska, Aleksandra; Toropainen, Maija; Ollgren, Jukka; Lyytikäinen, Outi; Nuorti, J. Pekka

2017-01-01

Objectives Bacterial meningitis remains an important cause of morbidity and mortality worldwide. Its epidemiological characteristics, however, are changing due to new vaccines and secular trends. Conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae (10-valent) were introduced in 1986 and 2010 in Finland. We assessed the disease burden and long-term trends of five common causes of bacterial meningitis in a population-based observational study. Methods A case was defined as isolation of S. pneumoniae, Neisseria meningitidis, Streptococcus agalactiae, Listeria monocytogenes or H. influenzae from cerebrospinal fluid and reported to national, population-based laboratory surveillance system during 1995–2014. We evaluated changes in incidence rates (Poisson or negative binomial regression), case fatality proportions (χ2) and age distribution of cases (Wilcoxon rank-sum). Results During 1995–2014, S. pneumoniae and N. meningitidis accounted for 78% of the total 1361 reported bacterial meningitis cases. H. influenzae accounted for 4% of cases (92% of isolates were non-type b). During the study period, the overall rate of bacterial meningitis per 1 00 000 person-years decreased from 1.88 cases in 1995 to 0.70 cases in 2014 (4% annual decline (95% CI 3% to 5%). This was primarily due to a 9% annual reduction in rates of N. meningitidis (95% CI 7% to 10%) and 2% decrease in S. pneumoniae (95% CI 1% to 4%). The median age of cases increased from 31 years in 1995–2004 to 43 years in 2005–2014 (p=0.0004). Overall case fatality proportion (10%) did not change from 2004 to 2009 to 2010–2014. Conclusions Substantial decreases in bacterial meningitis were associated with infant conjugate vaccination against pneumococcal meningitis and secular trend in meningococcal meningitis in the absence of vaccination programme. Ongoing epidemiological surveillance is needed to identify trends, evaluate serotype distribution, assess vaccine impact and develop future vaccination strategies. PMID:28592578

Cluster of Serogroup W135 Meningococci, Southeastern Florida, 2008–2009

PubMed Central

Mejia-Echeverry, Alvaro; Fiorella, Paul; Leguen, Fermin; Livengood, John; Kay, Robyn; Hopkins, Richard

2010-01-01

Recently, 14 persons in southeastern Florida were identified with Neisseria meningitidis serogroup W135 invasive infections. All isolates tested had matching or near-matching pulsed-field gel electrophoresis patterns and belonged to the multilocus sequence type 11 clonal complex. The epidemiologic investigation suggested recent endemic transmission of this clonal complex in southeastern Florida. PMID:20031054

A combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus at 3, 5 and 11 months of age: results of an open, randomized, controlled study.

PubMed

Vesikari, Timo; Forstén, Aino; Desole, Maria Guiseppina; Ferrera, Giuseppe; Caubet, Magalie; Mesaros, Narcisa; Boutriau, Dominique

2013-05-01

This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.

Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valentine, Jenny L.; Chen, Linxiao; Perregaux, Emily C.

The development of antibodies against specific glycan epitopes poses a significant challenge due to difficulties obtaining desired glycans at sufficient quantity and purity, and the fact that glycans are usually weakly immunogenic. To address this challenge, we leveraged the potent immunostimulatory activity of bacterial outer membrane vesicles (OMVs) to deliver designer glycan epitopes to the immune system. This approach involved heterologous expression of two clinically important glycans, namely polysialic acid (PSA) and Thomsen-Friedenreich antigen (T antigen) in hypervesiculating strains of non-pathogenic Escherichia coli. The resulting glycOMVs displayed structural mimics of PSA or T antigen on their surfaces, and induced highmore » titers of glycan-specific IgG antibodies following immunization in mice. In the case of PSA glycOMVs, serum antibodies potently killed Neisseria meningitidis serogroup B (MenB), whose outer capsule is PSA, in a serum bactericidal assay. These findings demonstrate the potential of glycOMVs for inducing class-switched, humoral immune responses against glycan antigens.« less

Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies

DOE PAGES

Valentine, Jenny L.; Chen, Linxiao; Perregaux, Emily C.; ...

2016-06-23

The development of antibodies against specific glycan epitopes poses a significant challenge due to difficulties obtaining desired glycans at sufficient quantity and purity, and the fact that glycans are usually weakly immunogenic. To address this challenge, we leveraged the potent immunostimulatory activity of bacterial outer membrane vesicles (OMVs) to deliver designer glycan epitopes to the immune system. This approach involved heterologous expression of two clinically important glycans, namely polysialic acid (PSA) and Thomsen-Friedenreich antigen (T antigen) in hypervesiculating strains of non-pathogenic Escherichia coli. The resulting glycOMVs displayed structural mimics of PSA or T antigen on their surfaces, and induced highmore » titers of glycan-specific IgG antibodies following immunization in mice. In the case of PSA glycOMVs, serum antibodies potently killed Neisseria meningitidis serogroup B (MenB), whose outer capsule is PSA, in a serum bactericidal assay. These findings demonstrate the potential of glycOMVs for inducing class-switched, humoral immune responses against glycan antigens.« less

Meningococcal meningitis C in Tamil Nadu, public health perspectives.

PubMed

David, Kirubah Vasandhi; Pricilla, Ruby Angeline; Thomas, Beeson

2014-01-01

Meningococcal meningitis has rarely been reported in Tamil Nadu. We report here two children diagnosed with meningococcal meningitis in Vellore, Tamil Nadu, on May 2014. The causative strain was Neisseria meningitidis serotype C. The role of the primary care physician in early diagnosis, appropriate referral, and preventive measures of this disease to the immediate family and community is stressed.

Rapid Field Response to a Cluster of Illnesses and Deaths - Sinoe County, Liberia, April-May, 2017.

PubMed

Doedeh, John; Frimpong, Joseph Asamoah; Yealue, Kwuakuan D M; Wilson, Himiede W; Konway, Youhn; Wiah, Samson Q; Doedeh, Vivian; Bao, Umaru; Seneh, George; Gorwor, Lawrence; Toe, Sylvester; Ghartey, Emmanuel; Larway, Lawrence; Gweh, Dedesco; Gonotee, Philemon; Paasewe, Thomas; Tamatai, George; Yarkeh, James; Smith, Samuel; Brima-Davis, Annette; Dauda, George; Monger, Thomas; Gornor-Pewu, Leleh W; Lombeh, Siafa; Naiene, Jeremias; Dovillie, Nathaniel; Korvayan, Mark; George, Geraldine; Kerwillain, Garrison; Jetoh, Ralph; Friesen, Suzanne; Kinkade, Carl; Katawera, Victoria; Amo-Addae, Maame; George, Roseline N; Gbanya, Miatta Z; Dokubo, E Kainne

2017-10-27

On April 25, 2017, the Sinoe County Health Team (CHT) notified the Liberia Ministry of Health (MoH) and the National Public Health Institute of Liberia of an unknown illness among 14 persons that resulted in eight deaths in Sinoe County. On April 26, the National Rapid Response Team and epidemiologists from CDC, the World Health Organization (WHO) and the African Field Epidemiology Network (AFENET) in Liberia were deployed to support the county-led response. Measures were immediately implemented to identify all cases, ascertain the cause of illness, and control the outbreak. Illness was associated with attendance at a funeral event, and laboratory testing confirmed Neisseria meningitidis in biologic specimens from cases. The 2014-2015 Ebola virus disease (Ebola) outbreak in West Africa devastated Liberia's already fragile health system, and it took many months for the country to mount an effective response to control the outbreak. Substantial efforts have been made to strengthen Liberia's health system to prevent, detect, and respond to health threats. The rapid and efficient field response to this outbreak of N. meningitidis resulted in implementation of appropriate steps to prevent a widespread outbreak and reflects improved public health and outbreak response capacity in Liberia.

[Laboratory surveillance for invasive meningococcal disease in Chile, 2006-2012].

PubMed

Araya, Pamela; Díaz, Janepsy; Seoane, Mabel; Fernández, Jorge; Terrazas, Solana; Canals, Andrea; Vaquero, Alejandra; Barra, Gisselle; Hormazábal, Juan C; Pidal, Paola; Valenzuela, M Teresa

2014-08-01

Laboratory surveillance of Invasive Meningococcal Disease (IMD) is performed by the Institute of Public Health of Chile. It confirms identification, classifies in serogroups and analyzes the genetic profiles of Neisseria meningitidis isolates from laboratories throughout the country. To show the results of this surveillance from 2006 to 2012. A descriptive data analysis of the confirmed cases of IMD and serological characterization, susceptibility and genetic profiles of the isolates. The analysis was disaggregated by serogroup, age and region. From 2006 to 2012, 486 isolates of N. meningitidis were confirmed. In 2011 a rise in IMD rates was observed due to an increase in W serogroup cases, mainly affecting children aged 5 years or less. Serogroup W became the most prevalent during 2012 (58.3%), replacing the historically prevalent serogroup B. Predominating strains belonged to ST-32 complex/ET-5 complex (40, 4% of strains) and ST-41/44 complex/ Lineage 3 (45, 9% of strains). Laboratory surveillance has allowed the early detection of increasing IMD caused by serogroup W, which is emergent in Chile. This information has reinforced the daily monitoring of new cases, in collaboration with all the clinical laboratories of the country.

The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells.

PubMed

Lee, Ciaran M; Cradick, Thomas J; Bao, Gang

2016-03-01

The clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system from Streptococcus pyogenes (Spy) has been successfully adapted for RNA-guided genome editing in a wide range of organisms. However, numerous reports have indicated that Spy CRISPR-Cas9 systems may have significant off-target cleavage of genomic DNA sequences differing from the intended on-target site. Here, we report the performance of the Neisseria meningitidis (Nme) CRISPR-Cas9 system that requires a longer protospacer-adjacent motif for site-specific cleavage, and present a comparison between the Spy and Nme CRISPR-Cas9 systems targeting the same protospacer sequence. The results with the native crRNA and tracrRNA as well as a chimeric single guide RNA for the Nme CRISPR-Cas9 system were also compared. Our results suggest that, compared with the Spy system, the Nme CRISPR-Cas9 system has similar or lower on-target cleavage activity but a reduced overall off-target effect on a genomic level when sites containing three or fewer mismatches are considered. Thus, the Nme CRISPR-Cas9 system may represent a safer alternative for precision genome engineering applications.

Vaccine development against Neisseria meningitidis

PubMed Central

Vogel, Ulrich; Claus, Heike

2011-01-01

Summary Meningococcal disease is communicable by close contact or droplet aerosols. Striking features are high case fatality rates and peak incidences of invasive disease in infants, toddlers and adolescents. Vaccine development is hampered by bacterial immune evasion strategies including molecular mimicry. As for Haemophilus influenzae and Streptococcus pneumoniae, no vaccine has therefore been developed that targets all serogroups of Neisseria meningitidis. Polysaccharide vaccines available both in protein conjugated and non‐conjugated form, have been introduced against capsular serogroups A, C, W‐135 and Y, but are ineffective against serogroup B meningococci, which cause a significant burden of disease in many parts of the world. Detoxified outer membrane vesicles are used since decades to elicit protection against epidemic serogroup B disease. Genome mining and biochemical approaches have provided astounding progress recently in the identification of immunogenic, yet reasonably conserved outer membrane proteins. As subcapsular proteins nevertheless are unlikely to immunize against all serogroup B variants, thorough investigation by surrogate assays and molecular epidemiology approaches are needed prior to introduction and post‐licensure of protein vaccines. Research currently addresses the analysis of life vaccines, meningococcus B polysaccharide modifications and mimotopes, as well as the use of N. lactamicaouter membrane vesicles. PMID:21255369

The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells

PubMed Central

Lee, Ciaran M; Cradick, Thomas J; Bao, Gang

2016-01-01

The clustered regularly-interspaced short palindromic repeats (CRISPR)—CRISPR-associated (Cas) system from Streptococcus pyogenes (Spy) has been successfully adapted for RNA-guided genome editing in a wide range of organisms. However, numerous reports have indicated that Spy CRISPR-Cas9 systems may have significant off-target cleavage of genomic DNA sequences differing from the intended on-target site. Here, we report the performance of the Neisseria meningitidis (Nme) CRISPR-Cas9 system that requires a longer protospacer-adjacent motif for site-specific cleavage, and present a comparison between the Spy and Nme CRISPR-Cas9 systems targeting the same protospacer sequence. The results with the native crRNA and tracrRNA as well as a chimeric single guide RNA for the Nme CRISPR-Cas9 system were also compared. Our results suggest that, compared with the Spy system, the Nme CRISPR-Cas9 system has similar or lower on-target cleavage activity but a reduced overall off-target effect on a genomic level when sites containing three or fewer mismatches are considered. Thus, the Nme CRISPR-Cas9 system may represent a safer alternative for precision genome engineering applications. PMID:26782639

Meningococcal disease, a clinical and epidemiological review.

PubMed

Batista, Rodrigo Siqueira; Gomes, Andréia Patrícia; Dutra Gazineo, Jorge Luiz; Balbino Miguel, Paulo Sérgio; Santana, Luiz Alberto; Oliveira, Lisa; Geller, Mauro

2017-11-01

Meningococcal disease is the acute infection caused by Neisseria meningitidis, which has humans as the only natural host. The disease is widespread around the globe and is known for its epidemical potential and high rates of lethality and morbidity. The highest number of cases of the disease is registered in the semi-arid regions of sub-Saharan Africa. In Brazil, it is endemic with occasional outbreaks, epidemics and sporadic cases occurring throughout the year, especially in the winter. The major epidemics of the disease occurred in Brazil in the 70's caused by serogroups A and C. Serogroups B, C and Y represent the majority of cases in Europe, the Americas and Australia. However, there has been a growing increase in serogroup W in some areas. The pathogen transmission happens for respiratory route (droplets) and clinically can lead to meningitis and sepsis (meningococcemia). The treatment is made with antimicrobial and supportive care. For successful prevention, we have some measures like vaccination, chemoprophylaxis and droplets' precautions. In this review, we have described and clarify clinical features of the disease caused by N. meningitidis regarding its relevance for healthcare professionals. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Electrochemical DNA sensor for Neisseria meningitidis detection.

PubMed

Patel, Manoj K; Solanki, Pratima R; Kumar, Ashok; Khare, Shashi; Gupta, Sunil; Malhotra, Bansi D

2010-08-15

Meningitis sensor based on nucleic acid probe of Neisseria meningitidis has been fabricated by immobilization of 5'-thiol end labeled single stranded deoxyribonucleic acid probe (ssDNA-SH) onto gold (Au) coated glass electrode. This ssDNA-SH/Au electrode hybridized with the genomic DNA (G-dsDNA/Au) and amplified DNA (PCR-dsDNA/Au) has been characterized using atomic force microscopy (AFM), Fourier transforms infrared spectroscopy (FT-IR) and electrochemical techniques. The ssDNA-SH/Au electrode can specifically detect upto 10-60 ng/microl of G-dsDNA-SH/Au and PCR-dsDNA-SH/Au of meningitis within 60s of hybridization time at 25 degrees C by cyclic voltammetry (CV) using methylene blue (MB) as electro-active DNA hybridization indicator. The values of sensitivities of the G-dsDNA-SH/Au and PCR-dsDNA-SH/Au electrodes have been determined as 0.0115 microA/ng cm(-2) and 0.0056 microA/ng cm(-2), respectively with regression coefficient (R) as 0.999. This DNA bioelectrode is stable for about 4 months when stored at 4 degrees C. Copyright 2010 Elsevier B.V. All rights reserved.

Outer membrane biogenesis in Escherichia coli, Neisseria meningitidis, and Helicobacter pylori: paradigm deviations in H. pylori

PubMed Central

Liechti, George; Goldberg, Joanna B.

2012-01-01

The bacterial pathogen Helicobacter pylori is capable of colonizing the gastric mucosa of the human stomach using a variety of factors associated with or secreted from its outer membrane (OM). Lipopolysaccharide (LPS) and numerous OM proteins have been shown to be involved in adhesion and immune stimulation/evasion. Many of these factors are essential for colonization and/or pathogenesis in a variety of animal models. Despite this wide array of potential targets present on the bacterial surface, the ability of H. pylori to vary its OM profile limits the effectiveness of vaccines or therapeutics that target any single one of these components. However, it has become evident that the proteins comprising the complexes that transport the majority of these molecules to the OM are highly conserved and often essential. The field of membrane biogenesis has progressed remarkably in the last few years, and the possibility now exists for targeting the mechanisms by which β-barrel proteins, lipoproteins, and LPS are transported to the OM, resulting in loss of bacterial fitness and significant altering of membrane permeability. In this review, the OM transport machinery for LPS, lipoproteins, and outer membrane proteins (OMPs) are discussed. While the principal investigations of these transport mechanisms have been conducted in Escherichia coli and Neisseria meningitidis, here these systems will be presented in the genetic context of ε proteobacteria. Bioinformatic analysis reveals that minimalist genomes, such as that of Helicobacter pylori, offer insight into the smallest number of components required for these essential pathways to function. Interestingly, in the majority of ε proteobacteria, while the inner and OM associated apparatus of LPS, lipoprotein, and OMP transport pathways appear to all be intact, most of the components associated with the periplasmic compartment are either missing or are almost unrecognizable when compared to their E. coli counterparts. Eventual targeting of these pathways would have the net effect of severely limiting the delivery/transport of components to the OM and preventing the bacterium's ability to infect its human host. PMID:22919621

Plasma interferon-gamma and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock.

PubMed

Bjerre, Anna; Brusletto, Berit; Høiby, Ernst Arne; Kierulf, Peter; Brandtzaeg, Petter

2004-02-01

To analyze plasma interferon-gamma and interleukin-10 concentrations in patients with systemic meningococcal disease and patients with severe Gram-positive septic shock caused by Streptococcus pneumoniae or Staphylococcus aureus. To study the in vitro cytokine (interferon-gamma and interleukin-10) responses in a whole blood model boosted with heat-killed Neisseria meningitidis, S. pneumoniae, and S. aureus before and after treatment with recombinant interleukin-10 or recombinant interferon-gamma. Experimental study. Laboratory. Plasma samples were collected from patients with systemic meningococcal disease (n = 66) and patients with severe Gram-positive septic shock caused by S. pneumoniae (n = 4) or S. aureus (n = 3). Whole blood was boosted with heat-killed N. meningitidis, S. pneumoniae, and S. aureus (1 x 106 colony forming units/mL), and plasmas were analyzed for interleukin-10 or interferon-gamma at 0, 5, 12, and 24 hrs. Furthermore, recombinant interleukin-10 or recombinant interferon-gamma was added before bacteria, and the effect on the secretion of interferon-gamma and interleukin-10, respectively, was analyzed after 24 hrs. The median concentration of interferon-gamma was 15 pg/mL and of interleukin-10 was 10,269 pg/mL in patients with meningococcal septic shock (n = 24) compared with median interferon-gamma concentration of 3400 pg/mL and interleukin-10 concentration of 465 pg/mL in patients with severe Gram-positive shock (p =.001). Increased interferon-gamma concentrations were associated with case fatality (p =.011). In a whole blood model we demonstrated that 1 x 106 colony forming units/mL of N. meningitidis induced more interleukin-10 but less interferon-gamma than S. pneumoniae. S. aureus induced minimal secretion of both cytokines. Recombinant interleukin-10 efficiently down-regulated the secretion of interferon-gamma, and vice versa, as shown in a whole blood model. We speculate whether high concentrations of interleukin-10 contribute to the low concentrations of interferon-gamma in fulminant meningococcal septicemia. In addition, it appears as if interferon-gamma plays a minor role in the pathophysiology of meningococcal septic shock.

A Survey of Serum Bactericidal Antibodies against Neisseria meningitidis Serogroups A, C, W and Y in Adolescents and Adults in the Republic of Korea.

PubMed

Kang, Jin-Han; Miao, Yan; Lee, SooYoung; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Jo, Dae Sun; Song, HyoYoung; Haag, Mendel

2016-03-01

This descriptive epidemiological study aimed to assess the prevalence of serum bactericidal antibodies against Neisseria meningitidis serogroups A, C, W and Y in adolescents and adults in the Republic of Korea. In total, 987 subjects aged 11-55 years from five geographical regions of Korea were included in the study. Human serum bactericidal assay (hSBA) was used to measure hSBA titres for serogroups A, C, W and Y. Percentages of subjects with hSBA titres ≥4 and ≥8, geometric mean titres (GMTs), and associated 95% confidence intervals (CIs), were estimated. Analysis was performed for the entire study population and stratified by age group or region. No statistical hypotheses were tested. The highest percentage of subjects with hSBA titres ≥8 was observed for serogroup W (74%), was similar for serogroups C (34%) and Y (36%), and was lowest for serogroup A (9%). The percentages of subjects with hSBA titres ≥4 were similar to those with hSBA titres ≥8 for all serogroups. GMTs were 2.56 µg/mL (serogroup A), 5.14 µg/mL (serogroup C), 22.63 µg/mL (serogroup W) and 5.28 µg/mL (serogroup Y). Similar trends in GMTs across serogroups were seen for individual regions and age groups. The highest GMTs for serogroups A, W and Y were recorded in the >19-29 years group, and for serogroup C in the >49-55 years group. Across all regions, GMTs were very similar for serogroups A, C and Y, while more variation was seen for serogroup W. In the Korean population, among Neisseria meningitidis serogroups A, C, W and Y, serum bactericidal antibodies were most prevalent against serogroup W and least prevalent against serogroup A. These trends were maintained across age groups and regions. The highest GMTs for serogroups A, W and Y were observed in the >19-29 years group. The reasons behind the observed differences in prevalence of bactericidal antibodies against the serogroups are currently not understood, although carriage and cross-reactivity of the assay may be important influences.

Storage and stability of IgG and IgM monoclonal antibodies dried on filter paper and utility in Neisseria meningitidis serotyping by Dot-blot ELISA.

PubMed

Ferraz, Aline S; Belo, Elza F T; Coutinho, Ligia M C C; Oliveira, Ana P; Carmo, Andréia M S; Franco, Daniele L; Ferreira, Tatiane; Yto, André Y; Machado, Marta S F; Scola, Monica C G; De Gaspari, Elizabeth

2008-03-06

A simple filter paper method was developed for, the transport and storage of monoclonal antibodies (Mabs) at room temperature or -20 degrees C after spotting on filter paper, for subsequent serotyping of outer membrane antigens of N.meningitidis by dot-blot ELISA. Monoclonal antibodies (Mabs) were spotted within a 0.5-1 cm diameter area of Whatman grade 903 paper, which were stored individually at room temperature or at -20 degrees C. These MAbs were stored and analyzed after periods of one week, 4 weeks, 12 months, or 13 years in the case of frozen Mab aliquots, or after 4 weeks at -20 degrees C or at room temperature (RT) in the case of Mabs dried on filter paper strips. Assays were performed in parallel using dot-blot ELISA. In addition to the MAbs specific for serotyping class 1, 2 or 3, we used a larger number of Mabs for polysaccharides, lipooligosaccharides (LOS), class 5 and cross-reactive antigens for native outer membrane of N.meningitidis. The Mabs dried on filter paper were eluted with phosphate-buffered saline (PBS) containing 0.2% gelatin. Mabs of the isotypes IgG and IgM dried on filter papers were not affected by duration of storage. The detection by serotyping Mabs was generally consistent for dried filter paper MAb samples stored frozen for over 1 year at -20 degrees C, and although decreased reactive antibody titers were found after storage, this did not interfere with the specificity of the Mabs used after 13 years as dry spots on filter paper. The use of filter paper is an inexpensive and convenient method for collecting, storing, and transporting Mab samples for serotyping studies. In addition, the samples occupy little space and can be readily transported without freezing. The efficiency of using immunoglobulin G (IgG) or M (IgM) eluted was found to be consistent with measurement of IgG or IgM titers in most corresponding, ascites Mabs stored frozen for over 1 year. The application of meningococcal typing methods and designations depend on the question being asked.

Bacterial meningitis in Finland, 1995-2014: a population-based observational study.

PubMed

Polkowska, Aleksandra; Toropainen, Maija; Ollgren, Jukka; Lyytikäinen, Outi; Nuorti, J Pekka

2017-06-06

Bacterial meningitis remains an important cause of morbidity and mortality worldwide. Its epidemiological characteristics, however, are changing due to new vaccines and secular trends. Conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae (10-valent) were introduced in 1986 and 2010 in Finland. We assessed the disease burden and long-term trends of five common causes of bacterial meningitis in a population-based observational study. A case was defined as isolation of S. pneumoniae , Neisseria meningitidis , Streptococcus agalactiae , Listeria monocytogenes or H. influenzae from cerebrospinal fluid and reported to national, population-based laboratory surveillance system during 1995-2014. We evaluated changes in incidence rates (Poisson or negative binomial regression), case fatality proportions (χ 2 ) and age distribution of cases (Wilcoxon rank-sum). During 1995-2014, S. pneumoniae and N. meningitidis accounted for 78% of the total 1361 reported bacterial meningitis cases. H. influenzae accounted for 4% of cases (92% of isolates were non-type b). During the study period, the overall rate of bacterial meningitis per 1 00 000 person-years decreased from 1.88 cases in 1995 to 0.70 cases in 2014 (4% annual decline (95% CI 3% to 5%). This was primarily due to a 9% annual reduction in rates of N. meningitidis (95% CI 7% to 10%) and 2% decrease in S. pneumoniae (95% CI 1% to 4%). The median age of cases increased from 31 years in 1995-2004 to 43 years in 2005-2014 (p=0.0004). Overall case fatality proportion (10%) did not change from 2004 to 2009 to 2010-2014. Substantial decreases in bacterial meningitis were associated with infant conjugate vaccination against pneumococcal meningitis and secular trend in meningococcal meningitis in the absence of vaccination programme. Ongoing epidemiological surveillance is needed to identify trends, evaluate serotype distribution, assess vaccine impact and develop future vaccination strategies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Role of Oxidoreductases in Determining the Function of the Neisserial Lipid A Phosphoethanolamine Transferase Required for Resistance to Polymyxin

PubMed Central

Piek, Susannah; Wang, Zhirui; Ganguly, Jhuma; Lakey, Adam M.; Bartley, Stephanie N.; Mowlaboccus, Shakeel; Anandan, Anandhi; Stubbs, Keith A.; Scanlon, Martin J.; Vrielink, Alice; Azadi, Parastoo; Carlson, Russell W.; Kahler, Charlene M.

2014-01-01

The decoration of the lipid A headgroups of the lipooligosaccharide (LOS) by the LOS phosphoethanolamine (PEA) transferase (LptA) in Neisseria spp. is central for resistance to polymyxin. The structure of the globular domain of LptA shows that the protein has five disulphide bonds, indicating that it is a potential substrate of the protein oxidation pathway in the bacterial periplasm. When neisserial LptA was expressed in Escherichia coli in the presence of the oxidoreductase, EcDsbA, polymyxin resistance increased 30-fold. LptA decorated one position of the E. coli lipid A headgroups with PEA. In the absence of the EcDsbA, LptA was degraded in E. coli. Neisseria spp. express three oxidoreductases, DsbA1, DsbA2 and DsbA3, each of which appear to donate disulphide bonds to different targets. Inactivation of each oxidoreductase in N. meningitidis enhanced sensitivity to polymyxin with combinatorial mutants displaying an additive increase in sensitivity to polymyxin, indicating that the oxidoreductases were required for multiple pathways leading to polymyxin resistance. Correlates were sought between polymyxin sensitivity, LptA stability or activity and the presence of each of the neisserial oxidoreductases. Only meningococcal mutants lacking DsbA3 had a measurable decrease in the amount of PEA decoration on lipid A headgroups implying that LptA stability was supported by the presence of DsbA3 but did not require DsbA1/2 even though these oxidoreductases could oxidise the protein. This is the first indication that DsbA3 acts as an oxidoreductase in vivo and that multiple oxidoreductases may be involved in oxidising the one target in N. meningitidis. In conclusion, LptA is stabilised by disulphide bonds within the protein. This effect was more pronounced when neisserial LptA was expressed in E. coli than in N. meningitidis and may reflect that other factors in the neisserial periplasm have a role in LptA stability. PMID:25215579

Delayed Generalized Necrotic Purpuric Rash in a C6-Deficient 12-Year-Old Girl Treated for Group W Meningococcal Disease.

PubMed

Gaschignard, Jean; Hassani, Nailati; El Sissy, Carine; Bonacorsi, Stéphane; Dauger, Stéphane; Chomton, Maryline; Taha, Muhamed-Kheir; Levy, Michael

2018-02-22

We report an unusual case of generalized necrotic purpuric rash that started 48 hours after the initiation of effective third-generation cephalosporin therapy to treat Neisseria meningitidis W infection in a 12-year-old girl. The course was favorable with no shock, and she recovered completely without sequelae. This infection revealed C6 deficiency in our patient.

Nucleotide sequence composition and method for detection of neisseria gonorrhoeae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, A.; Yang, H.L.

1990-02-13

This patent describes a composition of matter that is specific for {ital Neisseria gonorrhoeae}. It comprises: at least one nucleotide sequence for which the ratio of the amount of the sequence which hybridizes to chromosomal DNA of {ital Neisseria gonorrhoeae} to the amount of the sequence which hybridizes to chromosomal DNA of {ital Neisseria meningitidis} is greater than about five. The ratio being obtained by a method described.

Combined Real-Time PCR and Pyrosequencing Strategy for Objective, Sensitive, Specific, and High-Throughput Identification of Reduced Susceptibility to Penicillins in Neisseria meningitidis▿

PubMed Central

Thulin, Sara; Olcén, Per; Fredlund, Hans; Unemo, Magnus

2008-01-01

A segment of penA in Neisseria meningitidis strains (n = 127), including two nucleotide sites closely associated to reduced susceptibility to penicillins, was amplified and pyrosequenced. All results were in concordance with Sanger sequencing, and a high correlation between alterations in the two Peni-specific sites and reduced susceptibility to penicillins was identified. PMID:18070955

Dynamics of the Murine Humoral Immune Response to Neisseria meningitidis Group B Capsular Polysaccharide

PubMed Central

Colino, Jesús; Outschoorn, Ingrid

1998-01-01

Immunization with Neisseria meningitidis group B capsular polysaccharide (CpsB) elicited responses in adult mice that showed the typical dynamic characteristics of the response to a thymus-independent antigen, in contrast to the thymus-dependent behavior of antibody responses to CpsC. The former had a short latent period and showed a rapid increase in serum antibodies that peaked at day 5, and immunoglobulin M (IgM) was the major isotype even though IgG (mainly IgG2a and IgG2b) was also detectable. This response was of short duration, and the specific antibodies were rapidly cleared from the circulation. The secondary responses were similar in magnitude, kinetics, IgM predominance, and IgG distribution. Nevertheless, a threefold IgG increase, a correlation between IgM and IgG levels, and dose-dependent secondary responses were observed. Hyperimmunization considerably reinforced these responses: 10-fold for IgM and 300-fold for IgG. This favored isotype switch was accompanied by a progressive change in the subclass distribution to IgG3 (62%) and IgG1 (28%), along with the possible generation of B-cell memory. The results indicate that CpsB is being strictly thymus independent and suggest that unresponsiveness to purified CpsB is due to tolerance. PMID:9453603

Protein carriers of conjugate vaccines

PubMed Central

Pichichero, Michael E

2013-01-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

Epidemiology of paediatric meningitis in central Côte d'Ivoire after the implementation of Haemophilus influenzae type b vaccination.

PubMed

Touré, Fidèle S; Kouame, Samson; Tia, Honoré; Monemo, Pacôme; Cissé, Amadou; Diané, Bamourou; Becker, Sören L; Akoua-Koffi, Chantal

2017-07-01

Infectious meningitis accounts for enormous morbidity worldwide, but there is a paucity of data on its regional epidemiology in resource-constrained settings of sub-Saharan Africa. Here, we present a study on the aetiology of paediatric meningitis in central Côte d'Ivoire. Between June 2012 and December 2013, all cerebrospinal fluid (CSF) samples drawn at the University Teaching Hospital Bouaké were examined for the presence of bacterial and fungal pathogens. A causative agent was detected in 31 out of 833 CSF specimens (3.7%), with the most prevalent pathogens being Streptococcus pneumoniae (n=15) and Neisseria meningitidis (n=5). With the exception of neonates, these two bacteria were the most common agents in all age groups. Of note, only a single case of Haemophilus influenzae meningitis was detected. Hence, this study reports a considerable shift in the epidemiology of paediatric meningitis in central Côte d'Ivoire. Following the implementation of a nation-wide childhood vaccination programme against H. influenzae type b, this pathogen was much less frequently reported than in previous studies. The integration of specific vaccines against S. pneumoniae and N. meningitidis into the childhood vaccination programme in Côted'Ivoire holds promise to further reduce the burden due to infectious meningitis.

A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine is immunogenic and induces immune memory when co-administered with DTPa-HBV-IPV and conjugate pneumococcal vaccines in infants.

PubMed

Nolan, Terry; Lambert, Stephen; Roberton, Don; Marshall, Helen; Richmond, Peter; Streeton, Catherine; Poolman, Jan; Boutriau, Dominique

2007-12-12

Immunogenicity and safety of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine (Hib-MenCY-TT) candidate was evaluated when co-administered with DTPa-HBV-IPV(Pediarix)+PCV7(Prevnar) at 2-4-6 months of age. Anti-PRP concentrations >or= 1.0 microg/mL were observed in 92.9-98.7%, rSBA-MenC/Y titres >or= 1:8 in >98%, rSBA-MenC/Y titres >or= 1:128 in >95.8 and >89.9% subjects. PRP and MenC responses were similar to respective controls (ActHIB and Menjugate) including for antibody persistence. Response to co-administered vaccines was not impaired. Polysaccharide challenge (PRP, PSC, PSY at 11-14 months of age) evidenced immune memory was induced for Hib, MenC/Y conjugate components. The safety profile of Hib-MenCY-TT was similar to controls. Hib-MenCY-TT administered according to the current US Hib vaccine schedule has the potential to induce protective antibodies against Hib and meningococcal-CY disease in infants and toddlers.

An antibacterial vaccination strategy based on a glycoconjugate containing the core lipopolysaccharide tetrasaccharide Hep2Kdo2

NASA Astrophysics Data System (ADS)

Kong, Lingbing; Vijayakrishnan, Balakumar; Kowarik, Michael; Park, Jin; Zakharova, Alexandra N.; Neiwert, Larissa; Faridmoayer, Amirreza; Davis, Benjamin G.

2016-03-01

Certain non-mammalian cell wall sugars are conserved across a variety of pathogenic bacteria. This conservation of structure, combined with their structural differences when compared with mammalian sugars, make them potentially powerful epitopes for immunization. Here, we report the synthesis of a glycoconjugate that displays the so-called ‘inner core’ sugars of Gram-negative bacterial cell walls. We also describe an antibacterial vaccination strategy based on immunization with the glycoconjugate and the subsequent administration of an inhibitor that uncovers the corresponding epitope in pathogenic bacteria. The core tetrasaccharide, Hep2Kdo2, a common motif in bacterial lipopolysaccharides, was synthesized and attached via a chain linker to a diphtheria toxin mutant carrier protein. This glycoconjugate generated titres of antibodies towards the inner core tetrasaccharide of the lipopolysaccharide, which were capable of binding the cell-surface sugars of bacterial pathogenic strains including Neisseria meningitidis, Pseudomonas aeruginosa and Escherichia coli. Exposure of bacterial lipopolysaccharide in in vitro experiments, using an inhibitor of capsular polysaccharide transport, enabled potent bacterial killing with antiserum.

Evolution of Sequence Type 4821 Clonal Complex Meningococcal Strains in China from Prequinolone to Quinolone Era, 1972–2013

PubMed Central

Guo, Qinglan; Mustapha, Mustapha M.; Chen, Mingliang; Qu, Di; Zhang, Xi; Harrison, Lee H.

2018-01-01

The expansion of hypervirulent sequence type 4821 clonal complex (CC4821) lineage Neisseria meningitidis bacteria has led to a shift in meningococcal disease epidemiology in China, from serogroup A (MenA) to MenC. Knowledge of the evolution and genetic origin of the emergent MenC strains is limited. In this study, we subjected 76 CC4821 isolates collected across China during 1972–1977 and 2005–2013 to phylogenetic analysis, traditional genotyping, or both. We show that successive recombination events within genes encoding surface antigens and acquisition of quinolone resistance mutations possibly played a role in the emergence of CC4821 as an epidemic clone in China. MenC and MenB CC4821 strains have spread across China and have been detected in several countries in different continents. Capsular switches involving serogroups B and C occurred among epidemic strains, raising concerns regarding possible increases in MenB disease, given that vaccines in use in China do not protect against MenB. PMID:29553310

Meningococcal groups C and Y and haemophilus B tetanus toxoid conjugate vaccine (HibMenCY-TT; MenHibrix(®)): a review.

PubMed

Perry, Caroline M

2013-05-01

The meningococcal groups C and Y and Haemophilus b (Hib) tetanus toxoid conjugate vaccine (HibMenCY-TT) contains Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens, and Hib capsular polysaccharide [polyribosyl-ribitol-phosphate (PRP)]. The HibMenCY-TT vaccine is available in the USA for use as active immunization to prevent invasive disease caused by N. meningitidis serogroups C (MenC) and Y (MenY), and Hib in children 6 weeks-18 months of age. HibMenCY-TT is the first meningococcal vaccine available for use in the USA that can be administered to infants as young as 6 weeks of age. In a randomized, controlled, phase III clinical trial, the HibMenCY-TT vaccine, administered to infants at 2, 4, 6 and 12-15 months of age, was immunogenic against MenC and MenY, and met the prespecified criteria for immunogenicity. Anti-PRP antibodies, which have been shown to correlate with protection against Hib invasive disease, were also induced in the infants who received the HibMenCY-TT vaccine, with induced levels of this antibody noninferior to those occurring in the control group of infants who received a Hib tetanus toxoid conjugate vaccine at 2, 4, and 6 months and a single dose of Hib conjugated to N. meningitidis outer membrane protein at 12-15 months. In several randomized, controlled clinical trials, HibMenCY-TT was coadministered with vaccines that are routinely administered to infants and toddlers in the USA. These vaccines included: diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined; 7-valent Streptococcus pneumoniae polysaccharide conjugate vaccine; measles, mumps and rubella vaccine; and varicella vaccine. Coadministration of these vaccines did not interfere with the immunogenicity of the HibMenCY-TT vaccine. Similarly, immune responses to the coadministered vaccines were not affected by the HibMenCY-TT vaccine. The tolerability profile of the HibMenCY-TT vaccine in infants and toddlers in the phase III trial was considered to be clinically acceptable and comparable to that of the Hib conjugate vaccines received by the control group.

Seroprevalence and placental transmission of maternal antibodies specific for Neisseria meningitidis Serogroups A, C, Y and W135 and influence of maternal antibodies on the immune response to a primary course of MenACWY-CRM vaccine in the United Kingdom.

PubMed

Blanchard-Rohner, Geraldine; Snape, Matthew D; Kelly, Dominic F; O'Connor, Daniel; John, Tessa; Kibwana, Elizabeth; Parks, Hannah; Ford, Karen; Dull, Peter M; Pollard, Andrew J

2013-07-01

Maternal antibodies give neonates some protection against bacterial infection. We measured antibodies against Neisseria meningitidis serogroups A, C, Y and W135 in mothers and their 2-month-old infants at study enrollment. We also assessed the impact of maternal antibody present at 2 months of age on the immune response to a primary course of quadrivalent meningococcal conjugate vaccine (MenACWY-CRM197) given at 2 and 4 months of age. This was a single-center, open-label, randomized study undertaken in Oxford, United Kingdom. Two hundred sixteen healthy infants were enrolled in the study and vaccinated with MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, in a subset of infants at 2 months and all infants at 5 months. Antibody and memory B-cell responses at 5 months were correlated with maternal antibodies. Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides, but high serogroup A antibody, whereas 61-78% had protective human complement serum bactericidal activity (hSBA) (≥1:4) for serogroups C, W135 and Y but only 31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-old infants had hSBA ≥1:4 for serogroups A, C, W135 and Y, respectively. Maternal antibody had little association on responses to MenACWY-CRM197, except a moderate negative association between MenC-specific bactericidal antibody at 2 and 5 months (r = -0.5, P = 0.006, n = 28) and between carrier-specific IgG antibody at 2 months and MenC-specific hSBA/IgG antibody at 5 months (r = -0.4, P = 0.02 and 0.04, n = 32 and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after vaccination at 2 and 4 months of age. The levels of serogroup-specific meningococcal antibodies were low in mothers and 2-month-old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.

A broad range assay for rapid detection and etiologic characterization of bacterial meningitis: performance testing in samples from sub-Sahara.

PubMed

Won, Helen; Yang, Samuel; Gaydos, Charlotte; Hardick, Justin; Ramachandran, Padmini; Hsieh, Yu-Hsiang; Kecojevic, Alexander; Njanpop-Lafourcade, Berthe-Marie; Mueller, Judith E; Tameklo, Tsidi Agbeko; Badziklou, Kossi; Gessner, Bradford D; Rothman, Richard E

2012-09-01

This study aimed to conduct a pilot evaluation of broad-based multiprobe polymerase chain reaction (PCR) in clinical cerebrospinal fluid (CSF) samples compared to local conventional PCR/culture methods used for bacterial meningitis surveillance. A previously described PCR consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by Gram typing, and pathogen-specific probes was designed targeting variable regions of the 16S rRNA gene. The diagnostic performance of the 16S rRNA assay in "127 CSF samples was evaluated in samples from patients from Togo, Africa, by comparison to conventional PCR/culture methods. Our probes detected Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Uniprobe sensitivity and specificity versus conventional PCR were 100% and 54.6%, respectively. Sensitivity and specificity of uniprobe versus culture methods were 96.5% and 52.5%, respectively. Gram-typing probes correctly typed 98.8% (82/83) and pathogen-specific probes identified 96.4% (80/83) of the positives. This broad-based PCR algorithm successfully detected and provided species level information for multiple bacterial meningitis agents in clinical samples. Copyright © 2012 Elsevier Inc. All rights reserved.

A broad range assay for rapid detection and etiologic characterization of bacterial meningitis: performance testing in samples from sub-Sahara☆, ☆☆,★

PubMed Central

Won, Helen; Yang, Samuel; Gaydos, Charlotte; Hardick, Justin; Ramachandran, Padmini; Hsieh, Yu-Hsiang; Kecojevic, Alexander; Njanpop-Lafourcade, Berthe-Marie; Mueller, Judith E.; Tameklo, Tsidi Agbeko; Badziklou, Kossi; Gessner, Bradford D.; Rothman, Richard E.

2012-01-01

This study aimed to conduct a pilot evaluation of broad-based multiprobe polymerase chain reaction (PCR) in clinical cerebrospinal fluid (CSF) samples compared to local conventional PCR/culture methods used for bacterial meningitis surveillance. A previously described PCR consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by Gram typing, and pathogen-specific probes was designed targeting variable regions of the 16S rRNA gene. The diagnostic performance of the 16S rRNA assay in “”127 CSF samples was evaluated in samples from patients from Togo, Africa, by comparison to conventional PCR/culture methods. Our probes detected Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Uniprobe sensitivity and specificity versus conventional PCR were 100% and 54.6%, respectively. Sensitivity and specificity of uniprobe versus culture methods were 96.5% and 52.5%, respectively. Gram-typing probes correctly typed 98.8% (82/83) and pathogen-specific probes identified 96.4% (80/83) of the positives. This broad-based PCR algorithm successfully detected and provided species level information for multiple bacterial meningitis agents in clinical samples. PMID:22809694

Cluster of invasive Neisseria meningitidis infections on a cruise ship, Italy, October 2012.

PubMed

Stefanelli, P; Fazio, C; Neri, A; Isola, P; Sani, S; Marelli, P; Martinelli, C; Mastrantonio, P; Pompa, M G

2012-12-13

We describe a cluster of four cases of invasive meningococcal disease that occurred on a cruise ship sailing along the Italian coast in October 2012. All four cases were hospitalised with severe illness and one of them died. This report illustrates the importance of rapid implementation of emergency control measures such as administration of prophylaxis to all crew members and passengers to prevent the spread of the disease in such a close environment.

Electrophoretic Characteristics of Outer Membrane Proteins of Neisseria meningitidis,

DTIC Science & Technology

1987-07-01

chemo-organotropic aerobic or facultative microbes, producing catalase and cytochrome oxidase (Morello and Bohnoff, 1980; Reyn, 1974). These bacteria...resolution, the porosity, pH , and TRIS and glycine concentrations in the stacking and separating gels were investigated. The UNCLASSIFIED UNCLASSIFIED /5...stacking gels were 1.7 cm in length and contained, 0.375 M Tris-HCl ( pH 8.8) and 0.1% SDS. The electrode buffer ( pH 8.3 ) consisted of 0.025 M Tris-HCI

Global epidemiology of invasive meningococcal disease

PubMed Central

2013-01-01

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made. PMID:24016339

Global epidemiology of invasive meningococcal disease.

PubMed

Jafri, Rabab Z; Ali, Asad; Messonnier, Nancy E; Tevi-Benissan, Carol; Durrheim, David; Eskola, Juhani; Fermon, Florence; Klugman, Keith P; Ramsay, Mary; Sow, Samba; Zhujun, Shao; Bhutta, Zulfiqar A; Abramson, Jon

2013-09-10

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made.

Arthritis secondary to meningococcal disease: A case series of 7 patients.

PubMed

Masson-Behar, Vanina; Jacquier, Hervé; Richette, Pascal; Ziza, Jean-Marc; Zeller, Valérie; Rioux, Christophe; Coustet, Baptiste; Dieudé, Philippe; Ottaviani, Sébastien

2017-07-01

Arthritis secondary to invasive meningococcemia is rare and has been described as a direct result of bacteremia or as immunoallergic-type arthritis, related to the immune complex. Only a few case series have been reported.This multicenter study aimed to describe the clinical characteristics and therapeutic outcomes of arthritis secondary to meningococcal infection.We performed a 5-year retrospective study. We included all patients with inflammatory joint symptoms and proven meningococcal disease defined by the identification of Neisseria meningitidis in blood, cerebrospinal fluid, or synovial fluid. Septic arthritis was defined by the identification of N meningitidis in joint fluid. Immune-mediated arthritis was considered to be arthritis occurring after at least 1 day of invasive meningococcal disease without positive joint fluid culture.A total of 7 patients (5 males) with joint symptoms and meningococcal disease were identified. The clinical presentation was mainly oligoarticular and the knee was the most frequent joint site. Five patients had septic arthritis and 4 had immune-mediated arthritis; 2 had septic arthritis followed by immune-mediated arthritis. Immune-mediated arthritis occurred 3 to 7 days after meningococcal meningitis, and treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) led to improvement without complications.Physicians must be vigilant to the different clinical presentations in patients with arthritis associated with invasive meningococcal disease. If immune-mediated arthritis is suspected, NSAIDs are usually efficient.

Structural analysis of substrate-mimicking inhibitors in complex with Neisseria meningitidis 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase - The importance of accommodating the active site water.

PubMed

Heyes, Logan C; Reichau, Sebastian; Cross, Penelope J; Jameson, Geoffrey B; Parker, Emily J

2014-12-01

3-Deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyses the first committed step of the shikimate pathway, which produces the aromatic amino acids as well as many other aromatic metabolites. DAH7PS catalyses an aldol-like reaction between phosphoenolpyruvate and erythrose 4-phosphate. Three phosphoenolpyruvate mimics, (R)-phospholactate, (S)-phospholactate and vinyl phosphonate [(E)-2-methyl-3-phosphonoacrylate], were found to competitively inhibit DAH7PS from Neisseria meningitidis, which is the pathogen responsible for bacterial meningitis. The most potent inhibitor was the vinyl phosphonate with a Ki value of 3.9±0.4μM. We report for the first time crystal structures of these compounds bound in the active site of a DAH7PS enzyme which reveals that the inhibitors bind to the active site of the enzyme in binding modes that mimic those of the predicted oxocarbenium and tetrahedral intermediates of the enzyme-catalysed reaction. Furthermore, the inhibitors accommodate the binding of a key active site water molecule. Together, these observations provide strong evidence that this active site water participates directly in the DAH7PS reaction, enabling the facial selectivity of the enzyme-catalysed reaction sequence to be delineated. Copyright © 2014 Elsevier Inc. All rights reserved.

Iron in Neisseria meningitidis: minimum requirements, effects of limitation, and characteristics of uptake.

PubMed Central

Archibald, F S; DeVoe, I W

1978-01-01

A simple defined medium (neisseria defined medium) was devised that does not require iron extraction to produce iron-limited growth of Neisseria meningitidis (SDIC). Comparison of this medium to Mueller-Hinton broth and agar showed nearly identical growth rates and yields. The defined medium was used in batch cultures to determine the disappearance of iron from the medium and its uptake by cells. To avoid a number of problems inherent in batch culture, continuous culture, in which iron and dissolved oxygen were varied independently, was used. Most of the cellular iron was found to be nonheme and associated with the particulate fraction in sonically disrupted cells. Nonheme and catalase-heme iron were reduced by iron starvation far more than cytochromes b and c and N,N,N',N'-tetramethylphenylenediamine-oxidase. The respiration rate and efficiency also decreased under iron limitation, whereas generation times increased. The iron-starved meningococcus took up iron by an energy-independent system operating in the first minute after an iron pulse and a slower energy-dependent system inhibited by respiratory poisons and an uncoupler. The energy-dependent system showed saturation kinetics and was stimulated nearly fourfold by iron privation. In addition, to determine the availability to the meningococcus of the iron in selected compounds, a sensitive assay was devised in which an iron-limited continuous culture was pulsed with the iron-containing compound. PMID:101516

Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP) Assay for the Detection of Bacterial Meningitis Pathogens

PubMed Central

Clancy, Eoin; Cormican, Martin; Boo, Teck Wee; Cunney, Robert

2018-01-01

Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP) offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD) and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae, N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology. PMID:29425124

Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP) Assay for the Detection of Bacterial Meningitis Pathogens.

PubMed

Higgins, Owen; Clancy, Eoin; Cormican, Martin; Boo, Teck Wee; Cunney, Robert; Smith, Terry J

2018-02-09

Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP) offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD) and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae , Neisseria meningitidis and Haemophilus influenzae . Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae , N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology.

Detection of Bacterial Meningitis Pathogens by PCR-Mass Spectrometry in Cerebrospinal Fluid.

PubMed

Jing-Zi, Piao; Zheng-Xin, He; Wei-Jun, Chen; Yong-Qiang, Jiang

2018-06-01

Acute bacterial meningitis remains a life-threatening infectious disease with considerable morbidity and mortality. DNA-based detection methods are an urgent requisite for meningitis-causing bacterial pathogens for the prevention of outbreaks and control of infections. We proposed a novel PCR-mass spectrometry (PCR-Mass) assay for the simultaneous detection of four meningitis-causing agents, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Mycobacterium tuberculosis in the present study. A total of 138 cerebrospinal fluid (CSF) samples (including 56 CSF culture positive, 44 CSF culture negative, and 38 CSF control) were enrolled and analyzed by PCR/Mass. Results were compared to real-time PCR detection. These four targeting pathogens could be discriminated without cross-reaction by the accurate detection of the corresponding extension products with different masses. The limits of detection were 102 copies/reaction for S. pneumoniae, H. influenzae, and N. meningitidis and 103 for M. tuberculosis. The evaluation of the culture-positive CSF specimens from the meningitis patients provided an overall agreement rate of 85.7% with PCR-Mass and real-time PCR. The PCR-Mass was also able to detect the targeting pathogens from culture-negative CSF specimens from meningitis patients receiving early antibiotic treatment. PCR-Mass could be used for the molecular detection of bacterial meningitis and tuberculosis, especially when early antibiotic treatment has been administered to the suspected patients.

Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design

PubMed Central

Andreae, Clio A.; Sessions, Richard B.; Virji, Mumtaz

2018-01-01

Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis. PMID:29547646

Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design.

PubMed

Andreae, Clio A; Sessions, Richard B; Virji, Mumtaz; Hill, Darryl J

2018-01-01

Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis.

Outer membrane vesicles (OMV) production of Neisseria meningitidis serogroup B in batch process.

PubMed

Santos, Sílvia; Arauz, Luciana Juncioni de; Baruque-Ramos, Júlia; Lebrun, Ivo; Carneiro, Sylvia Mendes; Barreto, Sandra Alves; Schenkman, Rocilda Perazzini Furtado

2012-09-14

Serogroup B outer membrane vesicles (OMV) with iron regulated proteins (IRP) from Neisseria meningitidis constitute the antigen for the vaccine against the disease caused by this bacterium. Aiming to enhance final OMV concentration, seven batch experiments were carried out under four different conditions: (i) with original Catlin medium; (ii) with original Catlin medium and lactate and amino acids pulse at the 6th cultivation hour; (iii) with Catlin medium with double initial concentrations of lactate and amino acids and (iv) Catlin medium without glycerol and with double initial concentrations of lactate and amino acids. The cultivation experiments were carried out in a 7-L bioreactor under the following conditions: 36°C, 0.5atm, overlay air 1L/min, agitation: 250-850 rpm, and O(2) control at 10%, 20 h. After lactate and amino acids exhaustion, cell growth reached stationary phase and a significant release increase of OMV was observed. According to the Luedeking & Piret model, OMV liberation is non-growth associated. Glycerol was not consumed during cultivation. The maximum OMV concentration value attained was 162 mg/L with correspondent productivity of 8.1mg/(Lh) employing Catlin medium with double initial concentrations of lactate and amino acids. The obtained OMV satisfied constitution and protein pattern criteria and were suitable for vaccine production. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quality by design approach in the development of an ultra-high-performance liquid chromatography method for Bexsero meningococcal group B vaccine.

PubMed

Nompari, Luca; Orlandini, Serena; Pasquini, Benedetta; Campa, Cristiana; Rovini, Michele; Del Bubba, Massimo; Furlanetto, Sandra

2018-02-01

Bexsero is the first approved vaccine for active immunization of individuals from 2 months of age and older to prevent invasive disease caused by Neisseria meningitidis serogroup B. The active components of the vaccine are Neisseria Heparin Binding Antigen, factor H binding protein, Neisseria adhesin A, produced in Escherichia coli cells by recombinant DNA technology, and Outer Membrane Vesicles (expressing Porin A and Porin B), produced by fermentation of Neisseria meningitidis strain NZ98/254. All the Bexsero active components are adsorbed on aluminum hydroxide and the unadsorbed antigens content is a product critical quality attribute. In this paper the development of a fast, selective and sensitive ultra-high-performance liquid chromatography (UHPLC) method for the determination of the Bexsero antigens in the vaccine supernatant is presented. For the first time in the literature, the Quality by Design (QbD) principles were applied to the development of an analytical method aimed to the quality control of a vaccine product. The UHPLC method was fully developed within the QbD framework, the new paradigm of quality outlined in International Conference on Harmonisation guidelines. Critical method attributes (CMAs) were identified with the capacity factor of Neisseria Heparin Binding Antigen, antigens resolution and peak areas. After a scouting phase, aimed at selecting a suitable and fast UHPLC operative mode for the vaccine antigens separation, risk assessment tools were employed to define the critical method parameters to be considered in the screening phase. Screening designs were applied for investigating at first the effects of vial type and sample concentration, and then the effects of injection volume, column type, organic phase starting concentration, ramp time and temperature. Response Surface Methodology pointed out the presence of several significant interaction effects, and with the support of Monte-Carlo simulations led to map out the design space, at a selected probability level, for the desired CMAs. The selected working conditions gave a complete separation of the antigens in about 5min. Robustness testing was carried out by a multivariate approach and a control strategy was implemented by defining system suitability tests. The method was qualified for the analysis of the Bexsero vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants.

PubMed

Martinon-Torres, Federico; Gimenez-Sanchez, Francisco; Bernaola-Iturbe, Enrique; Diez-Domingo, Javier; Jiang, Qin; Perez, John L

2014-09-08

Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed. This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase. Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were <39.0°C. Only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose. Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants. Copyright © 2014. Published by Elsevier Ltd.

The Many Faces of Meningococcal Disease: A Case Series and Review of Presentations and Treatment Options

DTIC Science & Technology

2004-01-01

United States. Classic findings include headache, fevers , and a petechial rash that begins on the lower extremities with a predilection for areas of...cough and sore throat, but no headache or fevers . He reported to the medical clinic at 9:00 a.m., 6 hours after the rash began. He was in acute...meningitidis septicemia (meningococcemia). Case 2 A 22-year-old active-duty female developed fevers , headaches, confusion, and a rash on her

[Antibiotic management of presumptive bacterial meningitis in adults (rational, methods, course, and follow-up)].

PubMed

Ansart, S

2009-01-01

The annual incidence of community acquired meningitis ranges between 0.6 and four per 100,000 adults in industrialized countries. The most common causative bacteria are Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes. The emergence of resistance to antibiotics, especially for S. pneumoniae, could explain the clinical failure of third generation cephalosporins used to treat adults with S. pneumoniae meningitis. The present therapeutic suggestions are more based on the extrapolation of an experimental model than on relevant clinical trials.

What about antibiotic resistance in Neisseria lactamica?

PubMed

Arreaza, L; Salcedo, C; Alcalá, B; Vázquez, J A

2002-03-01

The in vitro activity of penicillin, ampicillin, cefotaxime, ceftriaxone, rifampicin and ciprofloxacin against 286 Neisseria lactamica isolates was determined by agar dilution and the category of susceptibility was analysed in accordance with the criteria used for Neisseria meningitidis. All isolates were considered to have intermediate susceptibility to penicillin. A total of 1.7% of the isolates were resistant to ampicillin but all were susceptible to cefotaxime and ceftriaxone. Rifampicin MICs ranged between 0.12 and 2 mg/L. Six isolates (2.1%) showed decreased susceptibility to ciprofloxacin.

Outer membrane vesicles as platform vaccine technology

PubMed Central

Stork, Michiel; van der Ley, Peter

2015-01-01

Abstract Outer membrane vesicles (OMVs) are released spontaneously during growth by many Gram‐negative bacteria. They present a range of surface antigens in a native conformation and have natural properties like immunogenicity, self‐adjuvation and uptake by immune cells which make them attractive for application as vaccines against pathogenic bacteria. In particular with Neisseria meningitidis, they have been investigated extensively and an OMV‐containing meningococcal vaccine has recently been approved by regulatory agencies. Genetic engineering of the OMV‐producing bacteria can be used to improve and expand their usefulness as vaccines. Recent work on meningitis B vaccines shows that OMVs can be modified, such as for lipopolysaccharide reactogenicity, to yield an OMV product that is safe and effective. The overexpression of crucial antigens or simultaneous expression of multiple antigenic variants as well as the expression of heterologous antigens enable expansion of their range of applications. In addition, modifications may increase the yield of OMV production and can be combined with specific production processes to obtain high amounts of well‐defined, stable and uniform OMV particle vaccine products. Further improvement can facilitate the development of OMVs as platform vaccine product for multiple applications. PMID:26912077

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Kemin; Johnson, Parker M.; Stols, Lucy

Contact-dependent growth inhibition (CDI) is an important mechanism of intercellular competition between neighboring Gram-negative bacteria. CDI systems encode large surface-exposed CdiA effector proteins that carry a variety of C-terminal toxin domains (CdiA-CTs). All CDI +bacteria also produce CdiI immunity proteins that specifically bind to the cognate CdiA-CT and neutralize its toxin activity to prevent auto-inhibition. Here, the X-ray crystal structure of a CdiI immunity protein fromNeisseria meningitidisMC58 is presented at 1.45 Å resolution. The CdiI protein has structural homology to the Whirly family of RNA-binding proteins, but appears to lack the characteristic nucleic acid-binding motif of this family. Sequence homologymore » suggests that the cognate CdiA-CT is related to the eukaryotic EndoU family of RNA-processing enzymes. A homology model is presented of the CdiA-CT based on the structure of the XendoU nuclease fromXenopus laevis. Molecular-docking simulations predict that the CdiA-CT toxin active site is occluded upon binding to the CdiI immunity protein. Together, these observations suggest that the immunity protein neutralizes toxin activity by preventing access to RNA substrates.« less

Improved purification of native meningococcal porin PorB and studies on its structure/function.

PubMed

Massari, Paola; King, Carol A; MacLeod, Heather; Wetzler, Lee M

2005-12-01

The outer membrane protein PorB of Neisseria meningitidis is a pore-forming protein which has various effects on eukaryotic cells. It has been shown to (1) up-regulate the surface expression of the co-stimulatory molecule CD86 and of MHC class II (which are TLR2/MyD88 dependent and related to the porin's immune-potentiating ability), (2) be involved in prevention of apoptosis by modulating the mitochondrial membrane potential, and (3) form pores in eukaryotic cells. As an outer membrane protein, its native trimeric form isolation is complicated by its insoluble nature, requiring the presence of detergent throughout the whole procedure, and by its tight association with other outer membrane components, such as neisserial LOS or lipoproteins. In this study, an improved chromatographic purification method to obtain an homogeneous product free of endotoxin and lipoprotein is described, without loss of any of the above-mentioned properties of the porin. Furthermore, we have investigated the requirement of the native trimeric structure for the porin's activity. Inactivation of functional PorB trimers into non-functional monomers was achieved by incubation on ice. Thus, routine long- and medium-term storage at low temperature may be a cause of porin inactivation.

From Immunologically Archaic to Neoteric Glycovaccines

PubMed Central

Cavallari, Marco; De Libero, Gennaro

2017-01-01

Polysaccharides (PS) are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection. PMID:28134792

Adjuvant Effects Elicited by Novel Oligosaccharide Variants of Detoxified Meningococcal Lipopolysaccharides on Neisseria meningitidis Recombinant PorA Protein: A Comparison in Mice

PubMed Central

Mehta, Ojas H.; Norheim, Gunnstein; Hoe, J . Claire; Rollier, Christine S.; Nagaputra, Jerry C.; Makepeace, Katherine; Saleem, Muhammad; Chan, Hannah; Ferguson, David J. P.; Jones, Claire; Sadarangani, Manish; Hood, Derek W.; Feavers, Ian; Derrick, Jeremy P.; Pollard, Andrew J.; Moxon, E . Richard

2014-01-01

Neisseria meningitidis lipopolysaccharide (LPS) has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB) of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs) as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS), and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus) were immunized with a recombinant PorA P1.7-2,4 (rPorA) protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16), each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines. PMID:25545241

Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among Invasive Neisseria meningitidis Serogroup W Sequence Type (ST)-11 Strains.

PubMed

Mustapha, Mustapha M; Marsh, Jane W; Krauland, Mary G; Fernandez, Jorge O; de Lemos, Ana Paula S; Dunning Hotopp, Julie C; Wang, Xin; Mayer, Leonard W; Lawrence, Jeffrey G; Hiller, N Luisa; Harrison, Lee H

2016-07-03

Neisseria meningitidis is an important cause of meningococcal disease globally. Sequence type (ST)-11 clonal complex (cc11) is a hypervirulent meningococcal lineage historically associated with serogroup C capsule and is believed to have acquired the W capsule through a C to W capsular switching event. We studied the sequence of capsule gene cluster (cps) and adjoining genomic regions of 524 invasive W cc11 strains isolated globally. We identified recombination breakpoints corresponding to two distinct recombination events within W cc11: A 8.4-kb recombinant region likely acquired from W cc22 including the sialic acid/glycosyl-transferase gene, csw resulted in a C→W change in capsular phenotype and a 13.7-kb recombinant segment likely acquired from Y cc23 lineage includes 4.5 kb of cps genes and 8.2 kb downstream of the cps cluster resulting in allelic changes in capsule translocation genes. A vast majority of W cc11 strains (497/524, 94.8%) retain both recombination events as evidenced by sharing identical or very closely related capsular allelic profiles. These data suggest that the W cc11 capsular switch involved two separate recombination events and that current global W cc11 meningococcal disease is caused by strains bearing this mosaic capsular switch. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Clonal Distribution of Disease-Associated and Healthy Carrier Isolates of Neisseria meningitidis between 1983 and 2005 in Cuba ▿

PubMed Central

Climent, Yanet; Yero, Daniel; Martinez, Isabel; Martín, Alejandro; Jolley, Keith A.; Sotolongo, Franklin; Maiden, Martin C. J.; Urwin, Rachel; Pajón, Rolando

2010-01-01

In response to epidemic levels of serogroup B meningococcal disease in Cuba during the 1980s, the VA-MENGOC-BC vaccine was developed and introduced into the National Infant Immunization Program in 1991. Since then the incidence of meningococcal disease in Cuba has returned to the low levels recorded before the epidemic. A total of 420 Neisseria meningitidis strains collected between 1983 and 2005 in Cuba were analyzed by multilocus sequence typing (MLST). The set of strains comprised 167 isolated from disease cases and 253 obtained from healthy carriers. By MLST analysis, 63 sequence types (STs) were identified, and 32 of these were reported to be a new ST. The Cuban isolates were associated with 12 clonal complexes; and the most common were ST-32 (246 isolates), ST-53 (86 isolates), and ST-41/44 (36 isolates). This study also showed that the application of VA-MENGOC-BC, the Cuban serogroup B and C vaccine, reduced the frequency and diversity of hypervirulent clonal complexes ST-32 (vaccine serogroup B type-strain) and ST-41/44 and also affected other lineages. Lineages ST-8 and ST-11 were no longer found during the postvaccination period. 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. PMID:20042619

Neisseria meningitidis and Streptococcus pneumoniae as leading causes of pediatric bacterial meningitis in nine Mexican hospitals following 3 years of active surveillance.

PubMed

Chacon-Cruz, Enrique; Martinez-Longoria, Cesar Adrian; Llausas-Magana, Eduardo; Luevanos-Velazquez, Antonio; Vazquez-Narvaez, Jorge Alejandro; Beltran, Sandra; Limon-Rojas, Ana Elena; Urtiz-Jeronimo, Fernando; Castaneda-Narvaez, Jose Luis; Otero-Mendoza, Francisco; Aguilar-Del Real, Fernando; Rodriguez-Chagoyan, Jesus; Rivas-Landeros, Rosa Maria; Volker-Soberanes, Maria Luisa; Hinojosa-Robles, Rosa Maria; Arzate-Barbosa, Patricia; Aviles-Benitez, Laura Karina; Elenes-Zamora, Fernando Ivan; Becka, Chandra M; Ruttimann, Ricardo

2016-01-01

Meningococcal meningitis is reported as a rare condition in Mexico. There are no internationally published studies on bacterial causes of meningitis in the country based on active surveillance. This study focuses on finding the etiology of bacterial meningitis in children from nine Mexican Hospitals. From January 2010 to February 2013, we conducted a three years of active surveillance for meningitis in nine hospitals throughout Mexico. Active surveillance started at the emergency department for every suspected case, and microbiological studies confirmed/ruled out all potentially bacterial pathogens. We diagnosed based on routine cultures from blood and cerebrospinal fluid (not polymerase chain reaction or other molecular diagnostic tests), and both pneumococcal serotyping and meningococcal serogrouping by using standard methods. Neisseria meningitidis was the leading cause, although 75% of cases occurred in the northwest of the country in Tijuana on the US border. Serogroup C was predominant. Streptococcus pneumoniae followed Neisseria meningitides, but was uniformly distributed throughout the country. Serotype 19A was the most incident but before universal implementation of the 13-valent pneumococcal conjugate vaccine. Other bacteria were much less common, including Enterobacteriaceae and Streptococcus agalactiae (these two affecting mostly young infants). Meningococcal meningitis is endemic in Tijuana, Mexico, and vaccination should be seriously considered in that region. Continuous universal vaccination with the 13-valent pneumococcal conjugate vaccine should be nationally performed, and polymerase chain reaction should be included for bacterial detection in all cultures - negative but presumably bacterial meningitis cases.

Bacterial meningitis in adults in Iceland, 1995-2010.

PubMed

Thornórðardóttir, Asgerður; Erlendsdóttir, Helga; Sigurðardóttir, Bryndís; Harðardóttir, Hjördís; Reynisson, Ingi Karl; Gottfreðsson, Magnús; Guðmundsson, Sigurður

2014-05-01

Bacterial meningitis is a serious disease with a mortality rate of 15-20% in adults. We conducted a population-based study of bacterial meningitis in adults (≥ 16 y) in Iceland, 1995-2010. Cases were identified based on positive bacterial cultures from cerebrospinal fluid (CSF) and/or the ICD codes for bacterial meningitis. Medical charts were reviewed and outcomes were assessed using the national population registry. The study period was divided into 2 equal parts, 1995-2002 and 2003-2010, before and after implementation of routine childhood vaccination against serogroup C meningococci, respectively. In total, 111 episodes occurred in 110 individuals. The most common causative organisms were Neisseria meningitidis (41%) and Streptococcus pneumoniae (30%). Only 30% of the patients presented with the classical symptom triad of fever, neck stiffness, and an altered mental status. The overall incidence was 3.2/100,000 inhabitants/y, and dropped significantly between the first and second halves of the study (p = 0.03). This drop was due to a reduced incidence of N. meningitidis meningitis: 34 and 12 cases in the first and second periods, respectively (p = 0.006). The incidence of meningitis caused by S. pneumoniae remained unchanged. The case fatality rates were 18% and 13% in the first and second halves of the study, respectively (difference not significant). The incidence of bacterial meningitis has decreased since the implementation of meningococcal C vaccination in 2002. However, the case fatality rate has remained unchanged.

Development of an FHbp-CTB holotoxin-like chimera and the elicitation of bactericidal antibodies against serogroup B Neisseria meningitidis.

PubMed

Price, Gregory A; Bash, Margaret C

2018-01-29

The Neisseria meningitidis factor H binding protein (FHbp) is an important virulence factor and vaccine antigen contained in both USA licensed serogroup B meningococcal vaccines. Recent studies in human factor H (hFH) transgenic mice suggest that hFH-FHbp interactions lower FHbp-elicited immunogenicity. To provide tools with which to characterize and potentially improve FHbp immunogenicity, we developed an FHbp-cholera holotoxin-like chimera vaccine expression system in Escherichia coli that utilizes cholera toxin B (CTB) as both a scaffold and adjuvant for FHbp. We developed FHbp-CTB chimeras using a wild-type (WT) FHbp and a low hFH-binding FHbp mutant R41S. Both chimeras bound to G M1 ganglioside and were recognized by the FHbp-specific monoclonal antibody JAR4. The R41S mutant had greatly reduced hFH binding compared to the WT FHbp-CTB chimera. WT and R41S FHbp-CTB chimeric antigens were compared to equimolar amounts of FHbp admixed with CTB or FHbp alone in mouse immunogenicity studies. The chimeras were significantly more immunogenic than FHbp alone or mixed with CTB, and elicited bactericidal antibodies against a panel of MenB isolates. This study demonstrates a unique and simple method for studying FHbp immunogenicity. The chimeric approach may facilitate studies of other protein-based antigens targeting pathogenic Neisseria and lay groundwork for the development of new protein based vaccines against meningococcal and gonococcal disease. Published by Elsevier Ltd.

Avidity of the Immunoglobulin G Response to a Neisseria meningitidis Group C Polysaccharide Conjugate Vaccine as Measured by Inhibition and Chaotropic Enzyme-Linked Immunosorbent Assays▿

PubMed Central

Harris, Shannon L.; Tsao, How; Ashton, Lindsey; Goldblatt, David; Fernsten, Philip

2007-01-01

Antibody avidity, the strength of the multivalent interaction between antibodies and their antigens, is an important characteristic of protective immune responses. We have developed an inhibition enzyme-linked immunosorbent assay (ELISA) to measure antibody avidity for the capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC) and determined the avidity constants (KDs) for 100 sera from children immunized with an MnC PS conjugate vaccine. The avidity constants were compared to the avidity indices (AI) obtained for the same sera using a chaotropic ELISA protocol. After the primary immunization series, the geometric mean (GM) KD was 674 nM and did not change in the months following immunization. However, the GM avidity did increase after the booster dose (GM KD, 414 nM 1 month after booster immunization). In contrast, the GM AI increased from an initial value of 118 after the primary immunization series to 147 6 months after the completion of the primary immunization series and then further increased to 178 after booster immunization. At the individual subject level, the avidity constant and AI correlated after the primary immunization series and after booster immunization but not prior to boosting. This work suggests that the AI, as measured by the chaotropic ELISA, in contrast to the KD, reflects changes that render antibody populations less susceptible to disruption by chaotropic agents without directly affecting the strength of the binding interactions. PMID:17287312

Triblock copolymer matrix-based capillary electrophoretic microdevice for high-resolution multiplex pathogen detection.

PubMed

Kim, Se Jin; Shin, Gi Won; Choi, Seok Jin; Hwang, Hee Sung; Jung, Gyoo Yeol; Seo, Tae Seok

2010-03-01

Rapid and simple analysis for the multiple target pathogens is critical for patient management. CE-SSCP analysis on a microchip provides high speed, high sensitivity, and a portable genetic analysis platform in molecular diagnostic fields. The capability of separating ssDNA molecules in a capillary electrophoretic microchannel with high resolution is a critical issue to perform the precise interpretation in the electropherogram. In this study, we explored the potential of poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO) triblock copolymer as a sieving matrix for CE-SSCP analysis on a microdevice. To demonstrate the superior resolving power of PEO-PPO-PEO copolymers, 255-bp PCR amplicons obtained from 16S ribosomal RNA genes of four bacterial species, namely Proteus mirabilis, Haemophilus ducreyi, Pseudomonas aeruginosa, and Neisseria meningitidis, were analyzed in the PEO-PPO-PEO matrix in comparison with 5% linear polyacrylamide and commercial GeneScan gel. Due to enhanced dynamic coating and sieving ability, PEO-PPO-PEO copolymer displayed fourfold enhancement of resolving power in the CE-SSCP to separate same-sized DNA molecules. Fivefold input of genomic DNA of P. aeruginosa and/or N. meningitidis produced proportionally increased corresponding amplicon peaks, enabling correct quantitative analysis in the pathogen detection. Besides the high-resolution sieving capability, a facile loading and replenishment of gel in the microchannel due to thermally reversible gelation property makes PEO-PPO-PEO triblock copolymer an excellent matrix in the CE-SSCP analysis on the microdevice.

Enhancing the Biological Relevance of Machine Learning Classifiers for Reverse Vaccinology.

PubMed

Heinson, Ashley I; Gunawardana, Yawwani; Moesker, Bastiaan; Hume, Carmen C Denman; Vataga, Elena; Hall, Yper; Stylianou, Elena; McShane, Helen; Williams, Ann; Niranjan, Mahesan; Woelk, Christopher H

2017-02-01

Reverse vaccinology (RV) is a bioinformatics approach that can predict antigens with protective potential from the protein coding genomes of bacterial pathogens for subunit vaccine design. RV has become firmly established following the development of the BEXSERO® vaccine against Neisseria meningitidis serogroup B. RV studies have begun to incorporate machine learning (ML) techniques to distinguish bacterial protective antigens (BPAs) from non-BPAs. This research contributes significantly to the RV field by using permutation analysis to demonstrate that a signal for protective antigens can be curated from published data. Furthermore, the effects of the following on an ML approach to RV were also assessed: nested cross-validation, balancing selection of non-BPAs for subcellular localization, increasing the training data, and incorporating greater numbers of protein annotation tools for feature generation. These enhancements yielded a support vector machine (SVM) classifier that could discriminate BPAs (n = 200) from non-BPAs (n = 200) with an area under the curve (AUC) of 0.787. In addition, hierarchical clustering of BPAs revealed that intracellular BPAs clustered separately from extracellular BPAs. However, no immediate benefit was derived when training SVM classifiers on data sets exclusively containing intra- or extracellular BPAs. In conclusion, this work demonstrates that ML classifiers have great utility in RV approaches and will lead to new subunit vaccines in the future.

Partial Purification and Characterization of Restriction Endonuclease from Neisseria meningitidis.

DTIC Science & Technology

1983-12-01

by centrifugation at 15,000 x g for 10 min. Preparation of Cell-Free Extract The cell pellet was suspended in 10 mL of Tris-HCI buffer pH 7.6 (Tris, 20...free extract (CFE) was obtained by centrifugation at 100,000 x g for I h. To the CFE, glycerol was added to a final concentration of 10% and stored at... extract obtained from N. meningilidis when incubated with A DNA and analyzed by agarose gel electrophoresis did not give a clean fragmentation pattern

Vaccine-preventable diseases and their impact on Latin American children.

PubMed

Ulloa-Gutierrez, Rolando; Miño, Greta; Odio, Carla; Avila-Aguero, María L; Brea, José

2011-12-01

A joint meeting of the Latin American Society of Pediatric Infectious Diseases, the Dominican Society of Pediatrics and the Dominican Society of Vaccinology was held in the Dominican Republic. This report highlights the most relevant issues that were presented and discussed about vaccine-preventable diseases, their epidemiology and impact in Latin American children, the need to move forward and expand national immunization programs and the economical and political obstacles to introduce 'new' vaccines. These include those against Streptococcus pneumoniae, rotavirus, hepatitis A, varicella, Neisseria meningitidis, Bordetella pertussis, influenza and human papillomavirus, among others.

Serogroup C Neisseria meningitidis invasive infection: analysis of the possible vaccination strategies for a mass campaign.

PubMed

Chiappini, Elena; Venturini, Elisabetta; Bonsignori, Francesca; Galli, Luisa; de Martino, Maurizio

2010-11-01

The serogroup C meningococcal conjugate vaccine is available since 1999. In the absence of randomized controlled trials that support a specific schedule, each country has adopted different vaccination programmes. Hereby, we analyse positive and negative aspects of the different vaccination strategies. While waiting for the introduction of other antimeningococcal vaccines, covering also for the Group B meningococci, further studies on effectiveness of an optimal schedule to be adopted in European countries are needed. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.

Characterization of diverse subvariants of the meningococcal factor H (fH) binding protein for their ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies.

PubMed

Seib, Kate L; Brunelli, Brunella; Brogioni, Barbara; Palumbo, Emmanuelle; Bambini, Stefania; Muzzi, Alessandro; DiMarcello, Federica; Marchi, Sara; van der Ende, Arie; Aricó, Beatrice; Savino, Silvana; Scarselli, Maria; Comanducci, Maurizio; Rappuoli, Rino; Giuliani, Marzia M; Pizza, Mariagrazia

2011-02-01

Neisseria meningitidis is a commensal of the human nasopharynx but is also a major cause of septicemia and meningitis. The meningococcal factor H binding protein (fHbp) binds human factor H (fH), enabling downregulation of complement activation on the bacterial surface. fHbp is a component of two serogroup B meningococcal vaccines currently in clinical development. Here we characterize 12 fHbp subvariants for their level of surface exposure and ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies. Flow cytometry and Western analysis revealed that all strains examined expressed fHbp on their surface to different extents and bound fH in an fHbp-dependent manner. However, differences in fH binding did not always correlate with the level of fHbp expression, indicating that this is not the only factor affecting the amount of fH bound. To overcome the issue of strain variability in fHbp expression, the MC58ΔfHbp strain was genetically engineered to express different subvariants from a constitutive heterologous promoter. These recombinant strains were characterized for fH binding, and the data confirmed that each subvariant binds different levels of fH. Surface plasmon resonance revealed differences in the stability of the fHbp-fH complexes that ranged over 2 orders of magnitude, indicating that differences in residues between and within variant groups can influence fH binding. Interestingly, the level of survival in human sera of recombinant MC58 strains expressing diverse subvariants did not correlate with the level of fH binding, suggesting that the interaction of fHbp with fH is not the only function of fHbp that influences serum resistance. Furthermore, cross-reactive bactericidal activity was seen within each variant group, although the degree of activity varied, suggesting that amino acid differences within each variant group influence the bactericidal antibody response.

The influence of mutation, recombination, population history, and selection on patterns of genetic diversity in Neisseria meningitidis.

PubMed

Jolley, K A; Wilson, D J; Kriz, P; McVean, G; Maiden, M C J

2005-03-01

Patterns of genetic diversity within populations of human pathogens, shaped by the ecology of host-microbe interactions, contain important information about the epidemiological history of infectious disease. Exploiting this information, however, requires a systematic approach that distinguishes the genetic signal generated by epidemiological processes from the effects of other forces, such as recombination, mutation, and population history. Here, a variety of quantitative techniques were employed to investigate multilocus sequence information from isolate collections of Neisseria meningitidis, a major cause of meningitis and septicemia world wide. This allowed quantitative evaluation of alternative explanations for the observed population structure. A coalescent-based approach was employed to estimate the rate of mutation, the rate of recombination, and the size distribution of recombination fragments from samples from disease-associated and carried meningococci obtained in the Czech Republic in 1993 and a global collection of disease-associated isolates collected globally from 1937 to 1996. The parameter estimates were used to reject a model in which genetic structure arose by chance in small populations, and analysis of molecular variation showed that geographically restricted gene flow was unlikely to be the cause of the genetic structure. The genetic differentiation between disease and carriage isolate collections indicated that, whereas certain genotypes were overrepresented among the disease-isolate collections (the "hyperinvasive" lineages), disease-associated and carried meningococci exhibited remarkably little differentiation at the level of individual nucleotide polymorphisms. In combination, these results indicated the repeated action of natural selection on meningococcal populations, possibly arising from the coevolutionary dynamic of host-pathogen interactions.

Etiologic Agents of Central Nervous System Infections among Febrile Hospitalized Patients in the Country of Georgia

PubMed Central

Akhvlediani, Tamar; Bautista, Christian T.; Shakarishvili, Roman; Tsertsvadze, Tengiz; Imnadze, Paata; Tatishvili, Nana; Davitashvili, Tamar; Samkharadze, Tamar; Chlikadze, Rusudan; Dvali, Natia; Dzigua, Lela; Karchava, Mariam; Gatserelia, Lana; Macharashvili, Nino; Kvirkvelia, Nana; Habashy, Engy Emil; Farrell, Margaret; Rowlinson, Emily; Sejvar, James; Hepburn, Matthew; Pimentel, Guillermo; Dueger, Erica; House, Brent; Rivard, Robert

2014-01-01

Objectives There is a large spectrum of viral, bacterial, fungal, and prion pathogens that cause central nervous system (CNS) infections. As such, identification of the etiological agent requires multiple laboratory tests and accurate diagnosis requires clinical and epidemiological information. This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis. Methods Children and adults patients clinically diagnosed with meningitis or encephalitis were enrolled at four reference health centers. Cerebrospinal fluid (CSF) was collected for bacterial culture, and in-house and multiplex RT-PCR testing was conducted for herpes simplex virus (HSV) types 1 and 2, mumps virus, enterovirus, varicella zoster virus (VZV), Streptococcus pneumoniae, HiB and Neisseria meningitidis. Results Out of 140 enrolled patients, the mean age was 23.9 years, and 58% were children. Bacterial or viral etiologies were determined in 51% of patients. Five Streptococcus pneumoniae cultures were isolated from CSF. Based on in-house PCR analysis, 25 patients were positive for S. pneumoniae, 6 for N. meningitidis, and 1 for H. influenzae. Viral multiplex PCR identified infections with enterovirus (n = 26), VZV (n = 4), and HSV-1 (n = 2). No patient was positive for mumps or HSV-2. Conclusions Study findings indicate that S. pneumoniae and enteroviruses are the main etiologies in this patient cohort. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve health outcomes of CNS infection cases in Georgia. PMID:25369023

Pathogen Identification by Multiplex LightMix Real-Time PCR Assay in Patients with Meningitis and Culture-Negative Cerebrospinal Fluid Specimens

PubMed Central

Wagner, Karoline; Springer, Burkard; Pires, Valeria P.

2017-01-01

ABSTRACT Acute bacterial meningitis is a medical emergency, and delays in initiating effective antimicrobial therapy result in increased morbidity and mortality. Culture-based methods, thus far considered the “gold standard” for identifying bacterial microorganisms, require 24 to 48 h to provide a diagnosis. In addition, antimicrobial therapy is often started prior to clinical sample collection, thereby decreasing the probability of confirming the bacterial pathogen by culture-based methods. To enable a fast and accurate detection of the most important bacterial pathogens causing meningitis, namely, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Streptococcus agalactiae, and Listeria monocytogenes, we evaluated a commercially available multiplex LightMix real-time PCR (RT-PCR) in 220 cerebrospinal fluid (CSF) specimens. The majority of CSF samples were collected by lumbar puncture, but we also included some CSF samples from patients with symptoms of meningitis from the neurology department that were recovered from shunts. CSF samples were analyzed by multiplex RT-PCR enabling a first diagnosis within a few hours after sample arrival at our institute. In contrast, bacterial identification took between 24 and 48 h by culture. Overall, a high agreement of bacterial identification between culture and multiplex RT-PCR was observed (99%). Moreover, multiplex RT-PCR enabled the detection of pathogens, S. pneumoniae (n = 2), S. agalactiae (n = 1), and N. meningitidis (n = 1), in four culture-negative samples. As a complement to classical bacteriological CSF culture, the LightMix RT-PCR assay proved to be valuable by improving the rapidity and accuracy of the diagnosis of bacterial meningitis. PMID:29237781

Neisseria meningitidis and Streptococcus pneumoniae as leading causes of pediatric bacterial meningitis in nine Mexican hospitals following 3 years of active surveillance

PubMed Central

Chacon-Cruz, Enrique; Martinez-Longoria, Cesar Adrian; Llausas-Magana, Eduardo; Luevanos-Velazquez, Antonio; Vazquez-Narvaez, Jorge Alejandro; Beltran, Sandra; Limon-Rojas, Ana Elena; Urtiz-Jeronimo, Fernando; Castaneda-Narvaez, Jose Luis; Otero-Mendoza, Francisco; Aguilar-Del Real, Fernando; Rodriguez-Chagoyan, Jesus; Rivas-Landeros, Rosa Maria; Volker-Soberanes, Maria Luisa; Hinojosa-Robles, Rosa Maria; Arzate-Barbosa, Patricia; Aviles-Benitez, Laura Karina; Elenes-Zamora, Fernando Ivan; Becka, Chandra M.; Ruttimann, Ricardo

2016-01-01

Objectives: Meningococcal meningitis is reported as a rare condition in Mexico. There are no internationally published studies on bacterial causes of meningitis in the country based on active surveillance. This study focuses on finding the etiology of bacterial meningitis in children from nine Mexican Hospitals. Methods: From January 2010 to February 2013, we conducted a three years of active surveillance for meningitis in nine hospitals throughout Mexico. Active surveillance started at the emergency department for every suspected case, and microbiological studies confirmed/ruled out all potentially bacterial pathogens. We diagnosed based on routine cultures from blood and cerebrospinal fluid (not polymerase chain reaction or other molecular diagnostic tests), and both pneumococcal serotyping and meningococcal serogrouping by using standard methods. Results: Neisseria meningitidis was the leading cause, although 75% of cases occurred in the northwest of the country in Tijuana on the US border. Serogroup C was predominant. Streptococcus pneumoniae followed Neisseria meningitides, but was uniformly distributed throughout the country. Serotype 19A was the most incident but before universal implementation of the 13-valent pneumococcal conjugate vaccine. Other bacteria were much less common, including Enterobacteriaceae and Streptococcus agalactiae (these two affecting mostly young infants). Conclusions: Meningococcal meningitis is endemic in Tijuana, Mexico, and vaccination should be seriously considered in that region. Continuous universal vaccination with the 13-valent pneumococcal conjugate vaccine should be nationally performed, and polymerase chain reaction should be included for bacterial detection in all cultures – negative but presumably bacterial meningitis cases. PMID:27551428

Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis

PubMed Central

Mustapha, Mustapha M.; Marsh, Jane W.; Krauland, Mary G.; Fernandez, Jorge O.; de Lemos, Ana Paula S.; Dunning Hotopp, Julie C.; Wang, Xin; Mayer, Leonard W.; Lawrence, Jeffrey G.; Hiller, N. Luisa; Harrison, Lee H.

2015-01-01

Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African ‘meningitis belt’ and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution. PMID:26629539

Phylogenetic relationships between some members of the genera Neisseria, Acinetobacter, Moraxella, and Kingella based on partial 16S ribosomal DNA sequence analysis.

PubMed

Enright, M C; Carter, P E; MacLean, I A; McKenzie, H

1994-07-01

We obtained 16S ribosomal DNA (rDNA) sequence data for strains belonging to 11 species of Proteobacteria, including the type strains of Kingella kingae, Neisseria lactamica, Neisseria meningitidis, Moraxella lacunata subsp. lacunata, [Neisseria] ovis, Moraxella catarrhalis, Moraxella osloensis, [Moraxella] phenylpyruvica, and Acinetobacter lwoffii, as well as strains of Neisseria subflava and Acinetobacter calcoaceticus. The data in a distance matrix constructed by comparing the sequences supported the proposal that the genera Acinetobacter and Moraxella and [N.] ovis should be excluded from the family Neisseriaceae. Our results are consistent with hybridization data which suggest that these excluded taxa should be part of a new family, the Moraxellaceae. The strains that we studied can be divided into the following five groups: (i) M. lacunata subsp. lacunata, [N.] ovis, and M. catarrhalis; (ii) M. osloensis; (iii) [M.] phenylpyruvica; (iv) A. calcoaceticus and A. lwoffii; and (v) N. meningitidis, N. subflava, N. lactamica, and K. kingae. We agree with the previous proposal that [N.] ovis should be renamed Moraxella ovis, as this organism is closely related to Moraxella species and not to Neisseria species. The generically misnamed taxon [M.] phenylpyruvica belongs to the proposed family Moraxellaceae, but it is sufficiently different to warrant exclusion from the genus Moraxella. Further work needs to be done to investigate genetically similar species, such as Psychrobacter immobilis, before the true generic position of this organism can be determined. Automated 16S rDNA sequencing with the PCR allows workers to accurately determine phylogenetic relationships between groups of organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternative Neisseria spp. type IV pilin glycosylation with a glyceramido acetamido trideoxyhexose residue

PubMed Central

Chamot-Rooke, Julia; Rousseau, Benoit; Lanternier, Fanny; Mikaty, Guillain; Mairey, Emilie; Malosse, Christian; Bouchoux, Guy; Pelicic, Vladimir; Camoin, Luc; Nassif, Xavier; Duménil, Guillaume

2007-01-01

The importance of protein glycosylation in the interaction of pathogenic bacteria with their host is becoming increasingly clear. Neisseria meningitidis, the etiological agent of cerebrospinal meningitis, crosses cellular barriers after adhering to host cells through type IV pili. Pilin glycosylation genes (pgl) are responsible for the glycosylation of PilE, the major subunit of type IV pili, with the 2,4-diacetamido-2,4,6-trideoxyhexose residue. Nearly half of the clinical isolates, however, display an insertion in the pglBCD operon, which is anticipated to lead to a different, unidentified glycosylation. Here the structure of pilin glycosylation was determined in such a strain by “top-down” MS approaches. MALDI-TOF, nanoelectrospray ionization Fourier transform ion cyclotron resonance, and nanoelectrospray ionization quadrupole TOF MS analysis of purified pili preparations originating from N. meningitidis strains, either wild type or deficient for pilin glycosylation, revealed a glycan mass inconsistent with 2,4-diacetamido-2,4,6-trideoxyhexose or any sugar in the databases. This unusual modification was determined by in-source dissociation of the sugar from the protein followed by tandem MS analysis with collision-induced fragmentation to be a hexose modified with a glyceramido and an acetamido group. We further show genetically that the nature of the sugar present on the pilin is determined by the carboxyl-terminal region of the pglB gene modified by the insertion in the pglBCD locus. We thus report a previously undiscovered monosaccharide involved in posttranslational modification of type IV pilin subunits by a MS-based approach and determine the molecular basis of its biosynthesis. PMID:17804791

Epidemiology of infant meningococcal disease in the United States, 2006-2012.

PubMed

MacNeil, Jessica R; Bennett, Nancy; Farley, Monica M; Harrison, Lee H; Lynfield, Ruth; Nichols, Megin; Petit, Sue; Reingold, Arthur; Schaffner, William; Thomas, Ann; Pondo, Tracy; Mayer, Leonard W; Clark, Thomas A; Cohn, Amanda C

2015-02-01

The incidence of meningococcal disease is currently at historic lows in the United States; however, incidence remains highest among infants aged <1 year. With routine use of Haemophilus influenzae type b and pneumococcal vaccines in infants and children in the United States, Neisseria meningitidis remains an important cause of bacterial meningitis in young children. Data were collected from active, population- and laboratory-based surveillance for N meningitidis conducted through Active Bacterial Core surveillance during 2006 through 2012. Expanded data collection forms were completed for infant cases identified in the surveillance area during 2006 through 2010. An estimated 113 cases of culture-confirmed meningococcal disease occurred annually among infants aged <1 year in the United States from 2006 through 2012, for an overall incidence of 2.74 per 100,000 infants. Among these cases, an estimated 6 deaths occurred. Serogroup B was responsible for 64%, serogroup C for 12%, and serogroup Y for 16% of infant cases. Based on the expanded data collection forms, a high proportion of infant cases (36/58, 62%) had a smoker in the household and the socioeconomic status of the census tracts where infant meningococcal cases resided was lower compared with the other Active Bacterial Core surveillance areas and the United States as a whole. The burden of meningococcal disease remains highest in young infants and serogroup B predominates. Vaccines that provide long-term protection early in life have the potential to reduce the burden of meningococcal disease, especially if they provide protection against serogroup B meningococcal disease. Copyright © 2015 by the American Academy of Pediatrics.

Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeys.

PubMed

Chabot, Donald J; Joyce, Joseph; Caulfield, Michael; Cook, James; Hepler, Robert; Wang, Su; Vietri, Nicholas J; Ruthel, Gordon; Shoop, Wesley; Pitt, Louise; Leffel, Elizabeth; Ribot, Wilson; Friedlander, Arthur M

2012-01-20

Bacillus anthracis, the causative agent of anthrax, is recognized as one of the most serious bioterrorism threats. The current human vaccines are based on the protective antigen component of the anthrax toxins. Concern about possible vaccine resistant strains and reliance on a single antigen has prompted the search for additional immunogens. Bacterial capsules, as surface-expressed virulence factors, are well-established components of several licensed vaccines. In a previous study we showed that an anthrax vaccine consisting of the B. anthracis poly-γ-D-glutamic acid capsule covalently conjugated to the outer membrane protein complex of Neisseria meningitidis serotype B protected mice against parenteral B. anthracis challenge. Here we tested this vaccine in rabbits and monkeys against an aerosol spore challenge. The vaccine induced anti-capsule antibody responses in both species, measured by ELISA and a macrophage opsono-adherence assay. While rabbits were not protected against a high aerosol challenge dose, significant protection was observed in monkeys receiving the capsule conjugate vaccine. The results confirm that the capsule is a protective immunogen against anthrax, being the first non-toxin antigen shown to be efficacious in monkeys and suggest that addition of capsule may broaden and enhance the protection afforded by protective antigen-based vaccines. Published by Elsevier Ltd.

A cluster of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup W among university students, France, February to May 2017

PubMed Central

Bassi, Clément; Taha, Muhamed-Kheir; Merle, Christian; Hong, Eva; Lévy-Bruhl, Daniel; Barret, Anne-Sophie; Mounchetrou Njoya, Ibrahim

2017-01-01

Between February and May 2017, two cases of invasive meningococcal disease caused by a new, rapidly expanding serogroup W meningococci variant were reported among students of an international university in Paris. Bacteriological investigations showed that isolates shared identical genotypic formula (W:P1.5,2:F1–1:cc11) and belonged to the South American/UK lineage. A vaccination campaign was organised that aimed at preventing new cases linked to potential persistence of the circulation of the bacteria in the students. PMID:28749333

[THE NATIONAL NUTRIENT MEDIUM FOR DIAGNOSTIC OF PURULENT BACTERIAL MENINGITIS].

PubMed

Podkopaev, Ya V; Domotenko, L V; Morozova, T P; Khramov, M K; Shepelin, A P

2015-05-01

The national growth mediums were developed for isolating and cultivating of main agents of purulent bacterial meningitis--haemophilus agar, chocolate agar, PBM-agar. The growing and selective characteristics of developed growth mediums are examined. The haemophilus agar ensures growth of Haemophilus influenzae. The chocolate agar, PBM-agar ensure growth of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. By growing characteristics, the national growth mediums match foreign analogues. Under application of growth mediums with selective additions it is possible to achieve selective isolation of main agents of purulent bacterial meningitis with inhibition of growth of microbes-associates.

Correction of localized shape errors on optical surfaces by altering the localized density of surface or near-surface layers

DOEpatents

Taylor, John S.; Folta, James A.; Montcalm, Claude

2005-01-18

Figure errors are corrected on optical or other precision surfaces by changing the local density of material in a zone at or near the surface. Optical surface height is correlated with the localized density of the material within the same region. A change in the height of the optical surface can then be caused by a change in the localized density of the material at or near the surface.

Microbial Community Profiling of Human Saliva Using Shotgun Metagenomic Sequencing

PubMed Central

Hasan, Nur A.; Young, Brian A.; Minard-Smith, Angela T.; Saeed, Kelly; Li, Huai; Heizer, Esley M.; McMillan, Nancy J.; Isom, Richard; Abdullah, Abdul Shakur; Bornman, Daniel M.; Faith, Seth A.; Choi, Seon Young; Dickens, Michael L.; Cebula, Thomas A.; Colwell, Rita R.

2014-01-01

Human saliva is clinically informative of both oral and general health. Since next generation shotgun sequencing (NGS) is now widely used to identify and quantify bacteria, we investigated the bacterial flora of saliva microbiomes of two healthy volunteers and five datasets from the Human Microbiome Project, along with a control dataset containing short NGS reads from bacterial species representative of the bacterial flora of human saliva. GENIUS, a system designed to identify and quantify bacterial species using unassembled short NGS reads was used to identify the bacterial species comprising the microbiomes of the saliva samples and datasets. Results, achieved within minutes and at greater than 90% accuracy, showed more than 175 bacterial species comprised the bacterial flora of human saliva, including bacteria known to be commensal human flora but also Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, and Gamma proteobacteria. Basic Local Alignment Search Tool (BLASTn) analysis in parallel, reported ca. five times more species than those actually comprising the in silico sample. Both GENIUSand BLAST analyses of saliva samples identified major genera comprising the bacterial flora of saliva, but GENIUS provided a more precise description of species composition, identifying to strain in most cases and delivered results at least 10,000 times faster. Therefore, GENIUS offers a facile and accurate system for identification and quantification of bacterial species and/or strains in metagenomic samples. PMID:24846174

Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old.

PubMed

Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai

2015-01-01

A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.

Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from Neisseria meningitidis serogroup B

PubMed Central

2013-01-01

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N. meningitidis B) using a dialysis procedure to produce them on lab scale. The immunogenicity of the AFCo1 produced by dialysis has been already evaluated, but it was necessary to demonstrate the feasibility of a larger-scale manufacturing process. Therefore, we used a crossflow diafiltration system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The aim of this work was to produce AFCo1 on pilot scale, while conserving the adjuvant properties. The proteoliposomes (raw material) were resuspended in a buffer containing sodium deoxycholate and were transformed into AFCo1 under the action of a calcium forming buffer. The detergent was removed from the protein solution by diafiltration to a constant volume. In this CFS, we used a hollow fiber cartridge from Amicon (polysulfona cartridge of 10 kDa porosity, 1mm channel diameter of fiber and 0.45 m2 area of filtration), allowing production of a batch of up to 20 L. AFCo1 were successfully produced by tangential filtration to pilot scale. The batch passed preliminary stability tests. Nasal immunization of BALB/c mice, induced specific saliva IgA and serum IgG. The induction of Th1 responses were demonstrated by the induction of IgG2a, IFNγ and not IL-5. The adjuvant action over Neisseria (self) antigens and with co-administered (heterologous) antigens such as ovalbumin and a synthetic peptide from haemolytic Streptococcus B was also demonstrated. PMID:23458578

Multicenter Study for Defining the Breakpoint for Rifampin Resistance in Neisseria meningitidis by rpoB Sequencing▿

PubMed Central

Taha, Muhamed-Kheir; Thulin Hedberg, Sara; Szatanik, Marek; Hong, Eva; Ruckly, Corinne; Abad, Raquel; Bertrand, Sophie; Carion, Francoise; Claus, Heike; Corso, Alejandra; Enríquez, Rocío; Heuberger, Sigrid; Hryniewicz, Waleria; Jolley, Keith A.; Kriz, Paula; Mollerach, Marta; Musilek, Martin; Neri, Arianna; Olcén, Per; Pana, Marina; Skoczynska, Anna; Sorhouet Pereira, Cecilia; Stefanelli, Paola; Tzanakaki, Georgina; Unemo, Magnus; Vázquez, Julio A.; Vogel, Ulrich; Wasko, Izabela

2010-01-01

Identification of clinical isolates of Neisseria meningitidis that are resistant to rifampin is important to avoid prophylaxis failure in contacts of patients, but it is hindered by the absence of a breakpoint for resistance, despite many efforts toward standardization. We examined a large number (n = 392) of clinical meningococcal isolates, spanning 25 years (1984 to 2009), that were collected in 11 European countries, Argentina, and the Central African Republic. The collection comprises all clinical isolates with MICs of ≥0.25 mg/liter (n = 161) received by the national reference laboratories for meningococci in the participating countries. Representative isolates displaying rifampin MICs of <0.25 mg/liter were also examined (n = 231). Typing of isolates was performed, and a 660-bp DNA fragment of the rpoB gene was sequenced. Sequences differing by at least one nucleotide were defined as unique rpoB alleles. The geometric mean of the MICs was calculated for isolates displaying the same allele. The clinical isolates displaying rifampin MICs of >1 mg/liter possessed rpoB alleles with nonsynonymous mutations at four critical amino acid residues, D542, H552, S548, and S557, that were absent in the alleles found in all isolates with MICs of ≤1 mg/liter. Rifampin-susceptible isolates could be defined as those with MICs of ≤1 mg/liter. The rpoB allele sequence and isolate data have been incorporated into the PubMLST Neisseria database (http://pubmlst.org/neisseria/). The rifampin-resistant isolates belonged to diverse genetic lineages and were associated with lower levels of bacteremia and inflammatory cytokines in mice. This biological cost may explain the lack of clonal expansion of these isolates. PMID:20606072

[Childhood bacterial meningitis in the Norwegian county Sør-Trøndelag 1988 - 2007].

PubMed

Skoe, Øyvind; Døllner, Henrik

2009-04-30

Bacterial meningitis is a severe and feared disease. We have studied bacterial meningitis in children in Sør-Trøndelag county during a 20-year period from 1988 to 2008. Medical records of children (in-patients) with spinal fluid findings or a clinical diagnosis of bacterial meningitis, at St. Olavs Hospital, were retrospectively reviewed. 112 cases of bacterial meningitis were registered in children below 16 years of age in Sør-Trøndelag county between 1988 and 2008. Children younger than 2 years had the highest occurrence, with a mean annual incidence of 42.3 per 100,000, whereas the incidence among children in the age group 2 to 16 was 5.7 per 100,000. We observed a decline in the occurrence from 19.1 per 100,000 in the period 1988 - 1991, to 6.9 per 100,000 in the period 2003 - 2006. 31 cases of Haemophilus influenzae type B, 26 cases of Neisseria meningitidis group B, 26 of Streptococcus pneumoniae and 19 cases with other pathogens were registered. The occurrence of H influenzae and N meningitidis have declined over the entire period, whereas S pneumoniae has increased. 6/112 children died (5.4 %) and 34 developed sequelae (30.4 %). In a multiple logistic regression analysis, the maximal value of C-reactive protein was associated with an increased risk of developing sequelae, adjusted for age and triggering microbe. The incidence of bacterial meningitis among children in Sør-Trøndelag has decreased significantly over the last 20 years, and meningitis is now a rare disease. Bacterial meningitis is most common among children below the age of two, and is still associated with a substantial mortality and risk of long-term neurological sequalae.

Preferential use of lambda light chains is associated with defective mouse antibody responses to the capsular polysaccharide of Neisseria meningitidis group B.

PubMed

Colino, Jesus; Outschoorn, Ingrid

2004-01-01

The capsular polysaccharide of Neisseria meningitidis group B (CpsB) is a very poor immunogen in mammals; this has been considered to be due to the induction of tolerance to cross-reactive host glycoconjugates. It has hampered the development of an effective vaccine against this meningococcal group for many years. Syngeneic populations have a similar tolerogenic background. Thus, we used the variability in ability to mount CpsB-specific immunoglobulin (Ig) responses of individuals from these populations to reveal underlying mechanisms to tolerance contributing to the poor immunogenicity of CpsB. Here we analyze by ELISA, the individual CpsB-specific Ig response of BALB/c and other syngeneic mice to immunization with intact bacteria, using the distribution of light chains as a direct indicator of the repertoire dynamics of the response. Although approximately 96% of anti-CpsB Ig bear kappa-light chains, BALB/c mouse populations were heterogeneous in the light chain composition of their individual anti-CpsB Ig responses. The proportion of kappa and lambda-light chains used for anti-CpsB Ig was a private characteristic that remained relatively constant, for each individual, through repetitive immunizations regardless of the bacterial stimuli size. Despite the prevalence of individual use of kappa-light chains, 5% of BALB/c mice showed restricted usage of lambda-light chains in their CpsB-specific Ig responses, and an additional 11% use them significantly. The preferential use of lambda-light chains in these mice was strongly associated with defective IgM, and absent or barely detectable IgG anti-CpsB responses even after repetitive bacterial immunization. We conclude that differences in the private repertoire of specific Ig also contribute to mouse unresponsiveness to CpsB.

Meningitis and Meningoencephalitis among Israel Defense Force Soldiers: 20 Years Experience at the Hadassah Medical Centers.

PubMed

Pikkel, Yoav Y; Ben-Hur, Tamir; Eliahou, Ruth; Honig, Asaf

2015-11-01

Meningitis and meningoencephalitis pose major risks of morbidity and mortality. To describe 20 years of experience treating infections of the central nervous system in Israel Defense Force (IDF) soldiers, including the common presentations, pathogens and sequelae, and to identify risk groups among soldiers. All soldiers who were admitted to the Hadassah University Medical Center (both campuses: Ein Kerem and Mt. Scopus) due to meningitis and meningoencephalitis from January 1993 to January 2014 were included in this retrospective study. Clinical, laboratory and radiologic data were reviewed from their hospital and army medical corps files. Attention was given to patients' military job description, i.e., combat vs. non-combat soldier, soldiers in training, and medical personnel. We identified 97 cases of suspected meningitis or meningoencephalitis. Six were mistakenly filed and these patients were found to have other disorders. Four soldiers were diagnosed with epidural abscess and five with meningitis due to non-infectious in flammatory diseases. Eighty-two soldiers in active and reserve duty had infectious meningitis or meningoencephalitis. Of these, 46 (56.1%) were combat soldiers and 31 (37.8%) non-combat; 20 (29.2%) were soldiers in training, 10 (12.2%) were training staff and 8 (9.8%) were medical staff. The main pathogens were enteroviruses, Epstein-Barr virus an d Neisseria meningitidis. In our series, soldiers in training, combat soldiers and medical personnel had meningitis and meningoencephalitis more than other soldiers. Enteroviruses are highly infectious pathogens and can cause outbreaks. N. meningitidis among IDF soldiers is still a concern. Early and aggressive treatment with steroids should be considered especially in robust meningoencephalitis cases.

Impact of calcium signaling during infection of Neisseria meningitidis to human brain microvascular endothelial cells.

PubMed

Asmat, Tauseef M; Tenenbaum, Tobias; Jonsson, Ann-Beth; Schwerk, Christian; Schroten, Horst

2014-01-01

The pili and outer membrane proteins of Neisseria meningitidis (meningococci) facilitate bacterial adhesion and invasion into host cells. In this context expression of meningococcal PilC1 protein has been reported to play a crucial role. Intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. Here we employed time lapse calcium-imaging and demonstrated that PilC1 of meningococci triggered a significant increase in cytoplasmic calcium in human brain microvascular endothelial cells, whereas PilC1-deficient meningococci could not initiate this signaling process. The increase in cytosolic calcium in response to PilC1-expressing meningococci was due to efflux of calcium from host intracellular stores as demonstrated by using 2-APB, which inhibits the release of calcium from the endoplasmic reticulum. Moreover, pre-treatment of host cells with U73122 (phospholipase C inhibitor) abolished the cytosolic calcium increase caused by PilC1-expressing meningococci demonstrating that active phospholipase C (PLC) is required to induce calcium transients in host cells. Furthermore, the role of cytosolic calcium on meningococcal adherence and internalization was documented by gentamicin protection assay and double immunofluorescence (DIF) staining. Results indicated that chelation of intracellular calcium by using BAPTA-AM significantly impaired PilC1-mediated meningococcal adherence to and invasion into host endothelial cells. However, buffering of extracellular calcium by BAPTA or EGTA demonstrated no significant effect on meningococcal adherence to and invasion into host cells. Taken together, these results indicate that meningococci induce calcium release from intracellular stores of host endothelial cells via PilC1 and cytoplasmic calcium concentrations play a critical role during PilC1 mediated meningococcal adherence to and subsequent invasion into host endothelial cells.

Laboratory-based surveillance of Neisseria meningitidis isolates from disease cases in Latin American and Caribbean countries, SIREVA II 2006-2010.

PubMed

Ibarz-Pavón, Ana Belén; Lemos, Ana Paula; Gorla, Maria Cecilia; Regueira, Mabel; Gabastou, Jean-Marc

2012-01-01

Published data on the epidemiology of meningococcal disease in Latin America and the Caribbean region is scarce and, when available, it is often published in Spanish and/or in non-peer-reviewed journals, making it difficult for the international scientific community to have access. Laboratory data on 4,735 Neisseria meningitidis strains was collected and reported by the National Reference Laboratories in 19 Latin American countries and the Caribbean Epidemiology Centre (CAREC) between 2006 and 2010 as part of the work carried out by the SIREVA II network. Serogroup and MIC to penicillin, rifampin and chloramphenicol were determined. Isolates were mainly obtained from patients <5 years, but each year around 25% of isolates came from adult patients. Serogroup distribution was highly variable among countries. Serogroup C was the main cause of disease in Brazil; the majority of disease seen in the Southern cone was caused by serogroup B, but serogroup W135 strains have increased in recent years. In the Andean and Mexico, Central America and Caribbean regions, serogroups B and C were equally present, and serogroup Y was frequently isolated. Isolates were generally susceptible to chloramphenicol, penicillin and rifampin, but almost 60% of isolates characterized in Southern cone countries presented intermediate resistance to penicillin. Five rifampin-resistant isolates have been isolated in Uruguay and Brazil. Serogroup distribution is highly variable among countries, but some geographic structuring can be inferred from these data. Epidemiological and laboratory data are scarce among Andean and Mexico, Central America and Caribbean countries. Evaluation and implementation of corrective measures on disease surveillance and reporting systems and the implementation of molecular diagnostic techniques and molecular characterization on meningococcal isolates are advised.

The First World War years of Sydney Domville Rowland: an early case of possible laboratory-acquired meningococcal disease.

PubMed

Wever, Peter C; Hodges, A J

2016-08-01

Sydney Domville Rowland was a bacteriologist and staff member at the Lister Institute of Preventive Medicine when the First World War broke out in 1914. Following a request to the Director of the Lister Institute to staff and equip a mobile field laboratory as quickly as possible, Rowland was appointed to take charge of No. 1 Mobile Laboratory and took up a temporary commission at the rank of Lieutenant in the Royal Army Medical Corps. On 9 October 1914, Rowland set out for the European mainland and was subsequently attached to General Headquarters in Saint-Omer, France (October 1914-June 1915), No. 10 Casualty Clearing Station in Lijssenthoek, Belgium (June 1915-February 1916, during which period he was promoted Major), and No. 26 General Hospital in Étaples, France (February 1916-March 1917). His research focused on gas gangrene, typhoid fever, trench fever, wound infection and cerebrospinal fever. In February of 1917, while engaged in identifying meningococcal carriers, Rowland contracted cerebrospinal meningitis to which he succumbed at age 44 on 6 March 1917. His untimely death might have been caused by laboratory-acquired meningococcal disease, especially since Rowland's work with Neisseria meningitidis isolates had extended beyond routine laboratory techniques and included risk procedures like immunisation of rabbits with pathogenic strains isolated from cerebrospinal fluid. Currently, microbiology laboratory workers who are routinely exposed to N. meningitidis isolates are recognised as a population at increased risk for meningococcal disease, for which reason recommended preventive measures include vaccination and handling of isolates within a class II biosafety cabinet. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Structural alterations in a component of cytochrome c oxidase and molecular evolution of pathogenic Neisseria in humans.

PubMed

Aspholm, Marina; Aas, Finn Erik; Harrison, Odile B; Quinn, Diana; Vik, Ashild; Viburiene, Raimonda; Tønjum, Tone; Moir, James; Maiden, Martin C J; Koomey, Michael

2010-08-19

Three closely related bacterial species within the genus Neisseria are of importance to human disease and health. Neisseria meningitidis is a major cause of meningitis, while Neisseria gonorrhoeae is the agent of the sexually transmitted disease gonorrhea and Neisseria lactamica is a common, harmless commensal of children. Comparative genomics have yet to yield clear insights into which factors dictate the unique host-parasite relationships exhibited by each since, as a group, they display remarkable conservation at the levels of nucleotide sequence, gene content and synteny. Here, we discovered two rare alterations in the gene encoding the CcoP protein component of cytochrome cbb(3) oxidase that are phylogenetically informative. One is a single nucleotide polymorphism resulting in CcoP truncation that acts as a molecular signature for the species N. meningitidis. We go on to show that the ancestral ccoP gene arose by a unique gene duplication and fusion event and is specifically and completely distributed within species of the genus Neisseria. Surprisingly, we found that strains engineered to express either of the two CcoP forms conditionally differed in their capacity to support nitrite-dependent, microaerobic growth mediated by NirK, a nitrite reductase. Thus, we propose that changes in CcoP domain architecture and ensuing alterations in function are key traits in successive, adaptive radiations within these metapopulations. These findings provide a dramatic example of how rare changes in core metabolic proteins can be connected to significant macroevolutionary shifts. They also show how evolutionary change at the molecular level can be linked to metabolic innovation and its reversal as well as demonstrating how genotype can be used to infer alterations of the fitness landscape within a single host.

Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer

PubMed Central

Brehony, Carina; O'Connor, Lois; Meyler, Kenneth; Jolley, Keith A.; Bray, James; Bennett, Desiree; Maiden, Martin C. J.; Cunney, Robert

2016-01-01

A carriage study was undertaken (n = 112) to ascertain the prevalence of Neisseria spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (n = 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled de novo and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (n = 8/14), persisting for at least 44 months, likely driven by the high population density of houses (n = 67/112) and trailers (n = 45/112). Carriage for Neisseria meningitidis (P < 0.05) and Neisseria lactamica (P < 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%, n = 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by Neisseria lactamica and Neisseria meningitidis. One HGT event resulted in the acquisition of 26 consecutive N. lactamica alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates. PMID:27629899

Phase Variation of NadA in Invasive Neisseria meningitidis Isolates Impacts on Coverage Estimates for 4C-MenB, a MenB vaccine.

PubMed

Green, Luke R; Lucidarme, Jay; Dave, Neelam; Chan, Hannah; Clark, Stephen; Borrow, Ray; Bayliss, Christopher D

2018-06-27

A recombinant NadA protein is one of the four major protective antigens of 4C-MenB (Bexsero®), a vaccine developed for serogroup B Neisseria meningitidis (MenB). The Meningococcal Antigen Typing System (MATS) is utilised as a high throughput assay for assessing the invasive MenB strain coverage of 4C-MenB. Where present, the nadA gene is subject to phase variable changes in transcription due to a 5'TAAA repeat tract located in a regulatory region. The promoter-containing intergenic region sequences (IGR) and 5'TAAA repeat numbers were determined for 906 invasive meningococcal disease isolates possessing the nadA gene. Exclusion of the 5'TAAA repeats reduced the number of IGR alleles from 82 to 23. Repeat numbers were associated with low and high levels of NadA expression by Western blotting and ELISA. Low expression repeat numbers were present in 83% of 179 MenB isolates with NadA-2/3 or Nad-1 peptide variants and 68% of 480 MenW ST-11 complex isolates with Nad-2/3 peptide variants. For isolates with vaccine-compatible NadA variants, 93% of MATS negative isolates were associated with low expression repeat numbers whereas 63% of isolates with MATS RP scores above the 95% confidence interval for the positive bactericidal threshold had high expression repeat numbers. Analysis of the 5'TAAA repeat number has potential as a rapid, high throughput method for assessing strain coverage for the NadA-component of 4C-MenB. A key application will be assessing coverage in meningococcal disease cases where confirmation is by PCR only and MATS cannot be applied. Copyright © 2018 Green et al.

The Meningitis Vaccine Project.

PubMed

LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

2007-09-03

Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world.

Immunoinformatics Approach in Designing Epitope-based Vaccine Against Meningitis-inducing Bacteria (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae Type b).

PubMed

Zahroh, Hilyatuz; Ma'rup, Ahmad; Tambunan, Usman Sumo Friend; Parikesit, Arli Aditya

2016-01-01

Meningitis infection is one of the major threats during Hajj season in Mecca. Meningitis vaccines are available, but their uses are limited in some countries due to religious reasons. Furthermore, they only give protection to certain serogroups, not to all types of meningitis-inducing bacteria. Recently, research on epitope-based vaccines has been developed intensively. Such vaccines have potential advantages over conventional vaccines in that they are safer to use and well responded to the antibody. In this study, we developed epitope-based vaccine candidates against various meningitis-inducing bacteria, including Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae type b. The epitopes were selected from their protein of polysaccharide capsule. B-cell epitopes were predicted by using BCPred, while T-cell epitope for major histocompatibility complex (MHC) class I was predicted using PAProC, TAPPred, and Immune Epitope Database. Immune Epitope Database was also used to predict T-cell epitope for MHC class II. Population coverage and molecular docking simulation were predicted against previously generated epitope vaccine candidates. The best candidates for MHC class I- and class II-restricted T-cell epitopes were MQYGDKTTF, MKEQNTLEI, ECTEGEPDY, DLSIVVPIY, YPMAMMWRNASNRAI, TLQMTLLGIVPNLNK, ETSLHHIPGISNYFI, and SLLYILEKNAEMEFD, which showed 80% population coverage. The complexes of class I T-cell epitopes-HLA-C*03:03 and class II T-cell epitopes-HLA-DRB1*11:01 showed better affinity than standards as evaluated from their Δ G binding value and the binding interaction between epitopes and HLA molecules. These peptide constructs may further be undergone in vitro and in vivo testings for the development of targeted vaccine against meningitis infection.

The spectrum of central nervous system infections in an adult referral hospital in Hanoi, Vietnam.

PubMed

Taylor, Walter R; Nguyen, Kinh; Nguyen, Duc; Nguyen, Huyen; Horby, Peter; Nguyen, Ha L; Lien, Trinh; Tran, Giang; Tran, Ninh; Nguyen, Ha M; Nguyen, Thai; Nguyen, Ha H; Nguyen, Thanh; Tran, Giap; Farrar, Jeremy; de Jong, Menno; Schultsz, Constance; Tran, Huong; Nguyen, Diep; Vu, Bich; Le, Hoa; Dao, Trinh; Nguyen, Trung; Wertheim, Heiman

2012-01-01

To determine prospectively the causative pathogens of central nervous system (CNS) infections in patients admitted to a tertiary referral hospital in Hanoi, Vietnam. From May 2007 to December 2008, cerebrospinal fluid (CSF) samples from 352 adults with suspected meningitis or encephalitis underwent routine testing, staining (Gram, Ziehl-Nielsen, India ink), bacterial culture and polymerase chain reaction targeting Neisseria meningitidis, Streptococcus pneumoniae, S. suis, Haemophilus influenzae type b, Herpes simplex virus (HSV), Varicella Zoster virus (VZV), enterovirus, and 16S ribosomal RNA. Blood cultures and clinically indicated radiology were also performed. Patients were classified as having confirmed or suspected bacterial (BM), tuberculous (TBM), cryptococcal (CRM), eosinophilic (EOM) meningitis, aseptic encephalitis/meningitis (AEM), neurocysticercosis and others. 352 (male: 66%) patients were recruited: median age 34 years (range 13-85). 95/352 (27.3%) diagnoses were laboratory confirmed and one by cranial radiology: BM (n = 62), TBM (n = 9), AEM (n = 19), CRM (n = 5), and neurocysticercosis (n = 1, cranial radiology). S. suis predominated as the cause of BM [48/62 (77.4%)]; Listeria monocytogenese (n = 1), S. pasteurianus (n = 1) and N. meningitidis (n = 2) were infrequent. AEM viruses were: HSV (n = 12), VZV (n = 5) and enterovirus (n = 2). 5 patients had EOM. Of 262/352 (74.4%) patients with full clinical data, 209 (79.8%) were hospital referrals and 186 (71%) had been on antimicrobials. 21 (8%) patients died: TBM (15.2%), AEM (10%), and BM (2.8%). Most infections lacked microbiological confirmation. S. suis was the most common cause of BM in this setting. Improved diagnostics are needed for meningoencephalitic syndromes to inform treatment and prevention strategies.

The Spectrum of Central Nervous System Infections in an Adult Referral Hospital in Hanoi, Vietnam

PubMed Central

Taylor, Walter R.; Nguyen, Kinh; Nguyen, Duc; Nguyen, Huyen; Horby, Peter; Nguyen, Ha L.; Lien, Trinh; Tran, Giang; Tran, Ninh; Nguyen, Ha M.; Nguyen, Thai; Nguyen, Ha H.; Nguyen, Thanh; Tran, Giap; Farrar, Jeremy; de Jong, Menno; Schultsz, Constance; Tran, Huong; Nguyen, Diep; Vu, Bich; Le, Hoa; Dao, Trinh; Nguyen, Trung; Wertheim, Heiman

2012-01-01

Objectives To determine prospectively the causative pathogens of central nervous system (CNS) infections in patients admitted to a tertiary referral hospital in Hanoi, Vietnam. Methods From May 2007 to December 2008, cerebrospinal fluid (CSF) samples from 352 adults with suspected meningitis or encephalitis underwent routine testing, staining (Gram, Ziehl-Nielsen, India ink), bacterial culture and polymerase chain reaction targeting Neisseria meningitidis, Streptococcus pneumoniae, S. suis, Haemophilus influenzae type b, Herpes simplex virus (HSV), Varicella Zoster virus (VZV), enterovirus, and 16S ribosomal RNA. Blood cultures and clinically indicated radiology were also performed. Patients were classified as having confirmed or suspected bacterial (BM), tuberculous (TBM), cryptococcal (CRM), eosinophilic (EOM) meningitis, aseptic encephalitis/meningitis (AEM), neurocysticercosis and others. Results 352 (male: 66%) patients were recruited: median age 34 years (range 13–85). 95/352 (27.3%) diagnoses were laboratory confirmed and one by cranial radiology: BM (n = 62), TBM (n = 9), AEM (n = 19), CRM (n = 5), and neurocysticercosis (n = 1, cranial radiology). S. suis predominated as the cause of BM [48/62 (77.4%)]; Listeria monocytogenese (n = 1), S. pasteurianus (n = 1) and N. meningitidis (n = 2) were infrequent. AEM viruses were: HSV (n = 12), VZV (n = 5) and enterovirus (n = 2). 5 patients had EOM. Of 262/352 (74.4%) patients with full clinical data, 209 (79.8%) were hospital referrals and 186 (71%) had been on antimicrobials. 21 (8%) patients died: TBM (15.2%), AEM (10%), and BM (2.8%). Conclusions Most infections lacked microbiological confirmation. S. suis was the most common cause of BM in this setting. Improved diagnostics are needed for meningoencephalitic syndromes to inform treatment and prevention strategies. PMID:22952590

Evaluation of meningitis surveillance before introduction of serogroup a meningococcal conjugate vaccine - Burkina Faso and Mali.

PubMed

2012-12-21

Each year, 450 million persons in a region of sub-Saharan Africa known as the "meningitis belt" are at risk for death and disability from epidemic meningitis caused by serogroup A Neisseria meningitidis. In 2009, the first serogroup A meningococcal conjugate vaccine (PsA-TT) developed solely for Africa (MenAfriVac, Serum Institute of India, Ltd.), was licensed for persons aged 1-29 years. During 2010-2011, the vaccine was introduced in the hyperendemic countries of Burkina Faso, Mali, and Niger through mass campaigns. Strong meningitis surveillance is critical for evaluating the impact of PsA-TT because it was licensed based on safety and immunogenicity data without field effectiveness trials. Case-based surveillance, which includes the collection of epidemiologic and laboratory data on individual cases year-round, is recommended for countries that aim to evaluate the vaccine's impact. A key component of case-based surveillance is expansion of laboratory confirmation to include every case of bacterial meningitis because multiple meningococcal serogroups and different pathogens such as Haemophilus influenzae type b and Streptococcus pneumoniae cause meningitis that is clinically indistinguishable from that caused by serogroup A Neisseria meningitidis. Before the introduction of PsA-TT, evaluations of the existing meningitis surveillance in Burkina Faso and Mali were conducted to assess the capacity for case-based surveillance. This report describes the results of those evaluations, which found that surveillance infrastructures were strong but opportunities existed for improving data management, handling of specimens shipped to reference laboratories, and laboratory capacity for confirming cases. These findings underscore the need to evaluate surveillance before vaccine introduction so that activities to strengthen surveillance are tailored to a country's needs and capacities.

[Meningitis and encephalitis in Poland in 2010].

PubMed

Parda, Natalia; Polkowska, Aleksandra

2012-01-01

Annually 2 000-3 000 cases of meningitis and encephalitis are notified to the Polish surveillance system. The leading etiologic agents of the bacterial infections are: N. meningitidis, S. pneumoniae, H. influenzae type B and L. monocytogenes. The most common causes of bacterial infections in children are: E. coli, S. agalactiae and H. influenzae type B. The viral infections are mainly caused by the following pathogens: Echovirus, Coxsackie virus group A and B. The agents responsible for the viral infections are also: arboviruses, Herpes simplex virus and mumps virus. The objectives of the present article are to analyze the epidemiology of meningitis and encephalitis in Poland in 2010 and to present the information on the vaccines used to prevent the discussed infections. The analysis was based on the data retrieved from the questionnaires used for the surveillance purposes, aggregated data on meningitis and encephalitis published in "Infectious diseases and poisonings in Poland in 2010", aggregated data on the vaccination coverage published in "Vaccinations in Poland in 2010", "Case definitions for the infectious diseases used for the surveillance purposes in 2009-2011" and Polish Immunization Programme for 2010. In 2010, Poland reported 3 063 neuroinfections--nearly 22% more than in 2009. The incidence rate was 8.03 cases per 100 000 population. From the analysis of data transpired that of the notified cases, 1 619 were of viral etiology, 846--were bacterial and 598 of other or unknown origin. Given the bacterial infections of determined etiology, the leading pathogenic agent was S. pneumoniae (180 cases), following by N. meningitidis (146 cases) and Haemophilus influenzae typu B (11 cases). Among confirmed cases of the viral infections, the predominant were tick-borne encephalitis cases (294). Compared to the data from 2009, the epidemiologic situation of the meningitis and encephalitis in Poland in 2010 has not changed significantly.

[Epidemiological characteristics of meningococcal meningitis in Guangxi Zhuang Autonomous Region during 1996 and 2007].

PubMed

Lin, Mei; Dong, Bai-Qing; Yang, Jin-Ye

2009-02-01

To analyze the epidemiological characteristics of meningococcal meningitis and provide evidences for disease control. The method of descriptive epidemiology has been used to analyze the data collected. A total of 419 cases were reported with meningococcal meningitis between 1996-2007, annual incidence rate was 0.07/100,000. 68 cases were dead and mortatity was 16.23% . Highly sporadic distribution by areas was observed in the cases reported. And the incidence peak was between January and April. The aged was mainly at 0-9 years There was trace that the incidence move to aged at 10 19 years old in recent years. The in-cidence rate was higher in male than that in female. And it was mainly attacked in peasants, students and children left-behined at home. Outbreaks had occasionally occurred in Guangxi. The first outbreak caused by Neisseria meningitidis group C in China was reported. The strains isola-ted mainly were with Neisseria meningitidis group A, which accounting for 61.53% of the strains,followed by group C(15. 38%)and Group B (7.69%). Group A was found to be 100% re-sistant to SMZ-TMP,and both group C and B were 100% resistant to sulfanilamide. 1.28% the prevalence of carrier was confirmed by the throat swabs. The positive rate of titer to group A and C were 29. 95o and 21. 720 respectively, and the mean titers were 4.57 microg/ml and 1.70 microg/ml re-spectively. The characteristics of Meningococcal meningitis are summarized as low incidence,high mortabity,highly sporadic distribution, grouping diversity and increasing incidence in older population. Comprehensive measures with the priority of vaccination is the key measure for meningococcal meningitis control.

The structure of lactoferrin-binding protein B from Neisseria meningitidis suggests roles in iron acquisition and neutralization of host defences

PubMed Central

Brooks, Cory L.; Arutyunova, Elena; Lemieux, M. Joanne

2014-01-01

Pathogens have evolved a range of mechanisms to acquire iron from the host during infection. Several Gram-negative pathogens including members of the genera Neisseria and Moraxella have evolved two-component systems that can extract iron from the host glycoproteins lactoferrin and transferrin. The homologous iron-transport systems consist of a membrane-bound transporter and an accessory lipoprotein. While the mechanism behind iron acquisition from transferrin is well understood, relatively little is known regarding how iron is extracted from lactoferrin. Here, the crystal structure of the N-terminal domain (N-lobe) of the accessory lipoprotein lactoferrin-binding protein B (LbpB) from the pathogen Neisseria meningitidis is reported. The structure is highly homologous to the previously determined structures of the accessory lipoprotein transferrin-binding protein B (TbpB) and LbpB from the bovine pathogen Moraxella bovis. Docking the LbpB structure with lactoferrin reveals extensive binding interactions with the N1 subdomain of lactoferrin. The nature of the interaction precludes apolactoferrin from binding LbpB, ensuring the specificity of iron-loaded lactoferrin. The specificity of LbpB safeguards proper delivery of iron-bound lactoferrin to the transporter lactoferrin-binding protein A (LbpA). The structure also reveals a possible secondary role for LbpB in protecting the bacteria from host defences. Following proteolytic digestion of lactoferrin, a cationic peptide derived from the N-terminus is released. This peptide, called lactoferricin, exhibits potent antimicrobial effects. The docked model of LbpB with lactoferrin reveals that LbpB interacts extensively with the N-terminal lactoferricin region. This may provide a venue for preventing the production of the peptide by proteolysis, or directly sequestering the peptide, protecting the bacteria from the toxic effects of lactoferricin. PMID:25286931

Specific detection of common pathogens of acute bacterial meningitis using an internally controlled tetraplex-PCR assay.

PubMed

Farahani, Hamidreza; Ghaznavi-Rad, Ehsanollah; Mondanizadeh, Mahdieh; MirabSamiee, Siamak; Khansarinejad, Behzad

2016-08-01

Accurate and timely diagnosis of acute bacterial meningitis is critical for antimicrobial treatment of patients. Although PCR-based methods have been widely used for the diagnosis of acute meningitis caused by bacterial pathogens, the main disadvantage of these methods is their high cost. This disadvantage has hampered the widespread use of molecular assays in many developing countries. The application of multiplex assays and "in-house" protocols are two main approaches that can reduce the overall cost of a molecular test. In the present study, an internally controlled tetraplex-PCR was developed and validated for the specific detection of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae in cerebrospinal fluid (CSF) samples. The analysis of a panel of other human pathogens showed no cross-reactivity in the assay. The analytical sensitivity of the in-house assay was 792.3 copies/ml, when all three bacteria were presentin the specimens. This value was calculated as 444.5, 283.7, 127.8 copies/ml when only S. pneumoniae, N. meningitidis and H. influenzae, respectively, were present. To demonstrate the diagnostic performance of the assay, a total of 150 archival CSF samples were tested and compared with a commercial multiplex real-time PCR kit. A diagnostic sensitivity of 92.8% and a specificity of 95.1% were determined for the present tetraplex-PCR assay. The results indicate that the established method is sensitive, specific and cost-effective, and can be used particularly in situations where the high cost of commercial kits prevents the use of molecular methods for the diagnosis of bacterial meningitis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of substrate modification and C-terminal truncation on the active site structure of substrate-bound heme oxygenase from Neisseriae meningitidis; A 1H NMR study†

PubMed Central

Peng, Dungeng; Satterlee, James D.; Ma, Li-Hua; Dallas, Jerry L.; Smith, Kevin M.; Zhang, Xuhong; Sato, Michihiko; La Mar, Gerd N.

2011-01-01

Heme oxygenase, HO, from the pathogenic bacterium N. meningitidis, NmHO, which secures host iron, shares many properties with mammalian HOs, but also exhibits some key differences. The crystal structure appears more compact and the crystal-undetected C-terminus interacts with substrate in solution. The unique nature of substrate-protein, specifically pyrrole-I/II-helix-2, peripheral interactions in NmHO are probed by 2D 1H NMR to reveal unique structural features controlling substrate orientation. The thermodynamics of substrate orientational isomerism are mapped for substrates with individual vinyl → methyl → hydrogen substitutions and with enzyme C-terminal deletions. NmHO exhibits significantly stronger orientational preference, reflecting much stronger and selective pyrrole-I/II interactions with the protein matrix, than in mammalian HOs. Thus, replacing bulky vinyls with hydrogens results in a 180° rotation of substrate about the α,γ-meso axis in the active site. A "collapse" of the substrate pocket as substrate size decreases is reflected in movement of helix-2 toward the substrate as indicated by significant and selective increased NOESY cross peak intensity, increase in steric Fe-CN tilt reflected in the orientation of the major magnetic axis, and decrease in steric constraints controlling the rate of aromatic ring reorientation. The active site of NmHO appears "stressed" for native protohemin and its "collapse" upon replacing vinyls by hydrogen leads to a factor ~102 increase in substrate affinity. Interaction of the C-terminus with the active site destabilizes the crystallographic protohemin orientation by ~0.7 kcal/mol, which is consistent with optimizing the His207-Asp27 H-bond. Implications of the active site "stress" for product release are discussed. PMID:21870860

In vivo adaptation and persistence of Neisseria meningitidis within the nasopharyngeal mucosa.

PubMed

Johswich, Kay O; McCaw, Shannon E; Islam, Epshita; Sintsova, Anna; Gu, Angel; Shively, John E; Gray-Owen, Scott D

2013-01-01

Neisseria meningitidis (Nme) asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa.

In Vivo Adaptation and Persistence of Neisseria meningitidis within the Nasopharyngeal Mucosa

PubMed Central

Johswich, Kay O.; McCaw, Shannon E.; Islam, Epshita; Sintsova, Anna; Gu, Angel; Shively, John E.; Gray-Owen, Scott D.

2013-01-01

Neisseria meningitidis (Nme) asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa. PMID:23935487

Chickenpox complicated by pneumococcal meningitis: a rare coinfection.

PubMed

Rebahi, H; Mouaffak, Y; Soraa, N; Younous, S

2014-11-01

Bacterial complications, particularly skin superinfections, are common during chickenpox. However, reports of acute bacterial meningitis associated with chickenpox are unusual and amount to only a very few observations. For the most part, they are caused by Neisseria meningitidis or Streptococcus pyogenes. We report an infrequent occurrence of pneumococcal meningitis 2 days after the onset of a chickenpox rash in a 7-year-old previously healthy boy. Based on data from the literature, we attempt to understand the possible mechanisms resulting in bacterial complications, particularly meningitis, during chickenpox and to determine the means to prevent it. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Factor H-binding protein, a unique meningococcal vaccine antigen.

PubMed

Pizza, Mariagrazia; Donnelly, John; Rappuoli, Rino

2008-12-30

GNA1870, also named factor H-binding protein (fHbp) or rLP-2086, is a genome-derived antigen and one of the components of a rationally designed vaccine against Neisseria meningitidis serogroup B, which has entered phase III clinical trials. It has been classified into three main non-cross-protective variant groups. GNA1870 has also been termed fHbp because of its ability to bind factor H, a key regulatory component of the alternative complement pathway. fHbp is important for survival in human blood, human sera, and in presence of antimicrobial peptides, independently of its expression level. All these properties make fHbp a unique vaccine antigen.

Prevalence and antimicrobial resistance pattern of bacterial meningitis in Egypt

PubMed Central

Shaban, Lamyaa; Siam, Rania

2009-01-01

Infectious diseases are the leading cause of morbidity and mortality in the developing world. In Egypt bacterial diseases constitute a great burden, with several particular bacteria sustaining the leading role of multiple serious infections. This article addresses profound bacterial agents causing a wide array of infections including but not limited to pneumonia and meningitis. The epidemiology of such infectious diseases and the prevalence of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are reviewed in the context of bacterial meningitis. We address prevalent serotypes in Egypt, antimicrobial resistance patterns and efficacy of vaccines to emphasize the importance of periodic surveillance for appropriate preventive and treatment strategies. PMID:19778428

Microbial glyoxalase enzymes: metalloenzymes controlling cellular levels of methylglyoxal.

PubMed

Sukdeo, Nicole; Honek, John F

2008-01-01

The glyoxalase system consists of two enzymes, glyoxalase I and glyoxalase II. This system is important in the detoxification of methylglyoxal. Detailed studies have determined that the glyoxalase I from Escherichia coli, Neisseria meningitidis and Yersinia pestis are maximally activated by Ni2+ and Co2+, and are inactive with Zn2+, a situation quite different from the human glyoxalase I enzyme, which is activated by Zn2+. Recent studies on the Pseudomonas aeruginosa genome have led to the characterization of three different glyoxalase I enzymes, two of which follow a Ni2+/Co2+ activation profile and the third exhibits a human-like preference for Zn2+.

History of meningococcal vaccines and their serological correlates of protection.

PubMed

Vipond, Caroline; Care, Rory; Feavers, Ian M

2012-05-30

For over a hundred years Neisseria meningitidis has been known to be one of the major causes of bacterial meningitis. However, effective vaccines were not developed until the latter part of the 20th century. The first of these were based on purified high molecular weight capsular polysaccharides and more recently the development of glycoconjugate vaccines has made paediatric immunisation programmes possible. The prevention of group B meningococcal disease has remained a challenge throughout this period. This review charts the history of the development of meningococcal vaccines and the importance of serological correlates of protection in their evaluation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pediatric vaccines on the horizon.

PubMed

Chávez-Bueno, Susana; Stull, Terrence L

2010-09-01

Vaccines have saved the lives of millions of children and continue to be essential interventions to control infectious diseases among people of all ages. The list of recommended vaccines for children has expanded in recent years; however, many viral, bacterial and parasitic infections remain a major cause of morbidity and mortality in children. Improved vaccines to prevent Streptococcus pneumoniae and Neisseria meningitidis infections in children will soon be available. Recent scientific advances are being applied to design new childhood vaccines affording enhanced efficacy, safety and tolerability. Financial barriers and other obstacles to adequate vaccine access need to be eliminated to assure coverage for all children and adolescents.

Phase 1 first-in-human studies of the reactogenicity and immunogenicity of a recombinant meningococcal NspA vaccine in healthy adults.

PubMed

Halperin, Scott A; Langley, Joanne M; Smith, Bruce; Wunderli, Peter; Kaufman, Lisa; Kimura, Alan; Martin, Denis

2007-01-05

Neisserial surface protein A (NspA) is a highly conserved, surface-exposed outer membrane protein of Neisseria meningitidis that has been shown to induce a bactericidal immune response in animals against all pathogenic Neisserial serogroups. Healthy 18-50-year-old adults were assigned to receive, in a dose escalating manner, 3 doses of 1 of 5 formulations of an experimental, unfolded, recombinant NspA (rNspA) vaccine or placebo, or 1 dose of commercially available quadravalent (A, C, Y, W-135) meningococcal polysaccharide vaccine (Menomune((R))). Adverse events were collected during the first week post-immunization, prior to the next dose and 1 month after the last dose. Serum for measurement of hematological and biochemical parameters and antibodies by enzyme immunoassay and bactericidal assay were measured before the first dose, prior to the second dose and 1 month after the last dose of vaccine. The rNspA vaccine was well tolerated by recipients. Injection-site pain was reported more frequently by recipients of the three highest doses of rNspA compared to placebo but at similar rates to the licensed meningococcal polysaccharide vaccine. Adverse events were reported less frequently after subsequent doses in the three-dose series. An antibody rise measured by enzyme immunoassay was elicited with a dose-related increase that reached a maximum with the 125mug dose. Prolongation of the dosing interval between the second and third dose appeared to be associated with increased antibody levels. No bactericidal antibodies were detected after any of the rNspA formulations. The unfolded rNspA meningococcal vaccine was well tolerated and immunogenic in healthy adult volunteers but did not elicit bactericidal antibodies.

Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial Pathogen Streptococcus pyogenes.

PubMed

Blom, Anna M; Magda, Michal; Kohl, Lisa; Shaughnessy, Jutamas; Lambris, John D; Ram, Sanjay; Ermert, David

2017-12-01

Bacteria can cause life-threatening infections, such as pneumonia, meningitis, or sepsis. Antibiotic therapy is a mainstay of treatment, although antimicrobial resistance has drastically increased over the years. Unfortunately, safe and effective vaccines against most pathogens have not yet been approved, and thus developing alternative treatments is important. We analyzed the efficiency of factor H (FH)6-7/Fc, a novel antibacterial immunotherapeutic protein against the Gram-positive bacterium Streptococcus pyogenes This protein is composed of two domains of complement inhibitor human FH (FH complement control protein modules 6 and 7) that bind to S. pyogenes , linked to the Fc region of IgG (FH6-7/Fc). FH6-7/Fc has previously been shown to enhance complement-dependent killing of, and facilitate bacterial clearance in, animal models of the Gram-negative pathogens Haemophilus influenzae and Neisseria meningitidis We hypothesized that activation of complement by FH6-7/Fc on the surface of Gram-positive bacteria such as S. pyogenes will enable professional phagocytes to eliminate the pathogen. We found that FH6-7/Fc alleviated S. pyogenes- induced sepsis in a transgenic mouse model expressing human FH ( S. pyogenes binds FH in a human-specific manner). Furthermore, FH6-7/Fc, which binds to protein H and selected M proteins, displaced FH from the bacterial surface, enhanced alternative pathway activation, and reduced bacterial blood burden by opsonophagocytosis in a C3-dependent manner in an ex vivo human whole-blood model. In conclusion, FH-Fc chimeric proteins could serve as adjunctive treatments against multidrug-resistant bacterial infections. Copyright © 2017 by The American Association of Immunologists, Inc.

Immunization with recombinant truncated Neisseria meningitidis-Macrophage Infectivity Potentiator (rT-Nm-MIP) protein induces murine antibodies that are cross-reactive and bactericidal for Neisseria gonorrhoeae.

PubMed

Humbert, María Victoria; Christodoulides, Myron

2018-05-23

Neisseria meningitidis (Nm) and N. gonorrhoeae (Ng) express a Macrophage Infectivity Potentiator (MIP, NMB1567/NEIS1487) protein in their outer membrane (OM). In this study, we prepared independent batches of liposomes (n = 3) and liposomes + MonoPhosphoryl Lipid A (MPLA) (n = 3) containing recombinant truncated Nm-MIP protein encoded by Allele 2 (rT-Nm-MIP, amino acids 22-142), and used these to immunize mice. We tested the hypothesis that independent vaccine batches showed similar antigenicity, and that antisera could recognise both meningococcal and gonococcal MIP and induce cross-species bactericidal activity. The different batches of M2 rT-Nm-MIP-liposomes ± MPLA showed no significant (P > 0.05) batch-to-batch variation in antigenicity. Anti-rT-Nm-MIP sera reacted equally and specifically with Nm-MIP and Ng-MIP in OM and on live bacterial cell surfaces. Specificity was shown by no antiserum reactivity with Δmip bacteria. Using human complement/serum bactericidal assays, anti-M2 rT-Nm-MIP sera killed homologous meningococcal serogroup B (MenB) strains (median titres of 32-64 for anti-rT-Nm-MIP-liposome sera; 128-256 for anti-rT-Nm-MIP-liposome + MPLA sera) and heterologous M1 protein-expressing MenB strains (titres of 64 for anti rT-Nm-MIP-liposome sera; 128-256 for anti-rT-Nm-MIP-liposome + MPLA sera). Low-level killing (P < 0.05) was observed for a MenB isolate expressing M7 protein (titres 4-8), but MenB strains expressing M6 protein were not killed (titre < 4-8). Killing (P < 0.05) was observed against MenC and MenW bacteria expressing homologous M2 protein (titres of 8-16) but not against MenA or MenY bacteria (titres < 4-8). Antisera to M2 rT-Nm-MIP showed significant (P < 0.05) cross-bactericidal activity against gonococcal strain P9-17 (expressing M35 Ng-MIP, titres of 64-512) and strain 12CFX_T_003 (expressing M10 Ng-MIP, titres 8-16) but not against FA1090 (expressing M8 Ng-MIP). As an alternative to producing recombinant protein, we engineered successfully the Nm-OM to express M2 Truncated-Nm-MIP, but lipooligosaccharide-extraction with Na-DOC was contra-indicated. Our data suggest that a multi-component vaccine containing a select number of Nm- and Ng-MIP type proteins would be required to provide broad coverage of both pathogens. Copyright © 2018. Published by Elsevier Ltd.

A high figure of merit localized surface plasmon sensor based on a gold nanograting on the top of a gold planar film

NASA Astrophysics Data System (ADS)

Zhang, Zu-Yin; Wang, Li-Na; Hu, Hai-Feng; Li, Kang-Wen; Ma, Xun-Peng; Song, Guo-Feng

2013-10-01

We investigate the sensitivity and figure of merit (FOM) of a localized surface plasmon (LSP) sensor with gold nanograting on the top of planar metallic film. The sensitivity of the localized surface plasmon sensor is 317 nm/RIU, and the FOM is predicted to be above 8, which is very high for a localized surface plasmon sensor. By employing the rigorous coupled-wave analysis (RCWA) method, we analyze the distribution of the magnetic field and find that the sensing property of our proposed system is attributed to the interactions between the localized surface plasmon around the gold nanostrips and the surface plasmon polarition on the surface of the gold planar metallic film. These findings are important for developing high FOM localized surface plasmon sensors.

The prevalence, serogroup distribution and risk factors of meningococcal carriage in adolescents and young adults in Turkey

PubMed Central

Tekin, Rahmi Tuna; Dinleyici, Ener Cagri; Ceyhan, Mehmet; Karbuz, Adem; Salman, Nuran; Sutçu, Murat; Kurugol, Zafer; Balliel, Yasemin; Celik, Melda; Hacimustafaoglu, Mustafa; Kuyucu, Necdet; Kondolot, Meda; Sensoy, Gülnar; Metin, Ozge; Kara, Soner Sertan; Dinleyici, Meltem; Kılıç, Omer; Bayhan, Cihangul; Gurbuz, Venhar; Aycan, Emre; Memedova, Aygun; Karli, Arzu; Bozlu, Gulçin; Celebi, Solmaz

2017-01-01

ABSTRACT The serogroup epidemiology of invasive meningococcal disease (IMD), which varies considerably by geographic region and immunization schedule, changes continuously. Meningococcal carriage data are crucial for assessing IMD epidemiology and designing f potential vaccination strategies. Meningococcal seroepidemiology in Turkey differs from that in other countries: serogroups W and B are the predominant strains for IMD during childhood, whereas no serogroup C cases were identified over the last 10 y and no adolescent peak for IMD was found. There is a lack of data on meningococcal carriage that represents the whole population. The aims of this multicenter study (12 cities in Turkey) were to evaluate the prevalence of Neisseria meningitidis carriage, the serogroup distribution and the related risk factors (educational status, living in a dormitory or student house, being a household contact with Hajj pilgrims, smoking, completion of military service, attending bars/clubs) in 1518 adolescents and young adults aged 10–24 y. The presence of N. meningitidis DNA was tested, and a serogroup analysis was performed using polymerase chain reaction. The overall meningococcal carriage rate was 6.3% (n = 96) in the study population. A serogroup distribution of the 96 N. meningitidis strains isolated from the nasopharyngeal specimens revealed serogroup A in 5 specimens (5.2%), serogroup B in 9 specimens (9.4%), serogroup W in 64 specimens (66.6%), and serogroup Y in 4 specimens (4.2%); 14 were classified as non-grouped (14.4%). No serogroup C cases were detected. The nasopharyngeal meningococcal carriage rate was 5% in the 10–14 age group, 6.4% in the 15–17 age-group, and 4.7% in the 18–20 age group; the highest carriage rate was found in the 21–24 age group (9.1%), which was significantly higher than those of the other age groups (p < 0.05). The highest carriage rate was found in 17-year-old adolescents (11%). The carriage rate was higher among the participants who had had close contact with Hajj/Umrah pilgrims (p < 0.01) or a history of upper respiratory tract infections over the past 3 months (p < 0.05). The nasopharyngeal carriage rate was 6.3% among adolescents and young adults in Turkey and was similar to the recent rates observed in the same age groups in other countries. The most prevalent serogroup was W, and no serogroup C cases were found. In conclusion, the present study found that meningococcal carriage reaches its peak level by age 17, the highest carriage rate was found in 21 - to 24 - year-olds and the majority of the carriage cases were due to serogroup W. Adolescents and young adult carriers seem to be a potential reservoir for the disease, and further immunization strategies, including adolescent immunization, may play a role in the control of IMD. PMID:28140784

The prevalence, serogroup distribution and risk factors of meningococcal carriage in adolescents and young adults in Turkey.

PubMed

Tekin, Rahmi Tuna; Dinleyici, Ener Cagri; Ceyhan, Mehmet; Karbuz, Adem; Salman, Nuran; Sutçu, Murat; Kurugol, Zafer; Balliel, Yasemin; Celik, Melda; Hacimustafaoglu, Mustafa; Kuyucu, Necdet; Kondolot, Meda; Sensoy, Gülnar; Metin, Ozge; Kara, Soner Sertan; Dinleyici, Meltem; Kılıç, Omer; Bayhan, Cihangul; Gurbuz, Venhar; Aycan, Emre; Memedova, Aygun; Karli, Arzu; Bozlu, Gulçin; Celebi, Solmaz

2017-05-04

The serogroup epidemiology of invasive meningococcal disease (IMD), which varies considerably by geographic region and immunization schedule, changes continuously. Meningococcal carriage data are crucial for assessing IMD epidemiology and designing f potential vaccination strategies. Meningococcal seroepidemiology in Turkey differs from that in other countries: serogroups W and B are the predominant strains for IMD during childhood, whereas no serogroup C cases were identified over the last 10 y and no adolescent peak for IMD was found. There is a lack of data on meningococcal carriage that represents the whole population. The aims of this multicenter study (12 cities in Turkey) were to evaluate the prevalence of Neisseria meningitidis carriage, the serogroup distribution and the related risk factors (educational status, living in a dormitory or student house, being a household contact with Hajj pilgrims, smoking, completion of military service, attending bars/clubs) in 1518 adolescents and young adults aged 10-24 y. The presence of N. meningitidis DNA was tested, and a serogroup analysis was performed using polymerase chain reaction. The overall meningococcal carriage rate was 6.3% (n = 96) in the study population. A serogroup distribution of the 96 N. meningitidis strains isolated from the nasopharyngeal specimens revealed serogroup A in 5 specimens (5.2%), serogroup B in 9 specimens (9.4%), serogroup W in 64 specimens (66.6%), and serogroup Y in 4 specimens (4.2%); 14 were classified as non-grouped (14.4%). No serogroup C cases were detected. The nasopharyngeal meningococcal carriage rate was 5% in the 10-14 age group, 6.4% in the 15-17 age-group, and 4.7% in the 18-20 age group; the highest carriage rate was found in the 21-24 age group (9.1%), which was significantly higher than those of the other age groups (p < 0.05). The highest carriage rate was found in 17-year-old adolescents (11%). The carriage rate was higher among the participants who had had close contact with Hajj/Umrah pilgrims (p < 0.01) or a history of upper respiratory tract infections over the past 3 months (p < 0.05). The nasopharyngeal carriage rate was 6.3% among adolescents and young adults in Turkey and was similar to the recent rates observed in the same age groups in other countries. The most prevalent serogroup was W, and no serogroup C cases were found. In conclusion, the present study found that meningococcal carriage reaches its peak level by age 17, the highest carriage rate was found in 21 - to 24 - year-olds and the majority of the carriage cases were due to serogroup W. Adolescents and young adult carriers seem to be a potential reservoir for the disease, and further immunization strategies, including adolescent immunization, may play a role in the control of IMD.

Neisseria Heparin Binding Antigen is targeted by the human alternative pathway C3-convertase

PubMed Central

Di Fede, Martina; Biagini, Massimiliano; Cartocci, Elena; Parillo, Carlo; Greco, Alessandra; Martinelli, Manuele; Marchi, Sara; Pezzicoli, Alfredo; Delany, Isabel

2018-01-01

Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein specific for Neisseria and constitutes one of the three main protein antigens of the Bexsero vaccine. Meningococcal and human proteases, cleave NHBA protein upstream or downstream of a conserved Arg-rich region, respectively. The cleavage results in the release of the C-terminal portion of the protein. The C-terminal fragment originating from the processing of meningococcal proteases, referred to as C2 fragment, exerts a toxic effect on endothelial cells altering the endothelial permeability. In this work, we reported that recombinant C2 fragment has no influence on the integrity of human airway epithelial cell monolayers, consistent with previous findings showing that Neisseria meningitidis traverses the epithelial barrier without disrupting the junctional structures. We showed that epithelial cells constantly secrete proteases responsible for a rapid processing of C2 fragment, generating a new fragment that does not contain the Arg-rich region, a putative docking domain reported to be essential for C2-mediated toxic effect. Moreover, we found that the C3-convertase of the alternative complement pathway is one of the proteases responsible for this processing. Overall, our data provide new insights on the cleavage of NHBA protein during meningococcal infection. NHBA cleavage may occur at different stages of the infection, and it likely has a different role depending on the environment the bacterium is interacting with. PMID:29579105

AgdbNet – antigen sequence database software for bacterial typing

PubMed Central

Jolley, Keith A; Maiden, Martin CJ

2006-01-01

Background Bacterial typing schemes based on the sequences of genes encoding surface antigens require databases that provide a uniform, curated, and widely accepted nomenclature of the variants identified. Due to the differences in typing schemes, imposed by the diversity of genes targeted, creating these databases has typically required the writing of one-off code to link the database to a web interface. Here we describe agdbNet, widely applicable web database software that facilitates simultaneous BLAST querying of multiple loci using either nucleotide or peptide sequences. Results Databases are described by XML files that are parsed by a Perl CGI script. Each database can have any number of loci, which may be defined by nucleotide and/or peptide sequences. The software is currently in use on at least five public databases for the typing of Neisseria meningitidis, Campylobacter jejuni and Streptococcus equi and can be set up to query internal isolate tables or suitably-configured external isolate databases, such as those used for multilocus sequence typing. The style of the resulting website can be fully configured by modifying stylesheets and through the use of customised header and footer files that surround the output of the script. Conclusion The software provides a rapid means of setting up customised Internet antigen sequence databases. The flexible configuration options enable typing schemes with differing requirements to be accommodated. PMID:16790057

Sub-diffraction Imaging via Surface Plasmon Decompression

DTIC Science & Technology

2014-06-08

of the local wavelength of a surface plasmon polariton supported by two adjoining curved metal surfaces. The views, opinions and/or findings...adiabatic decompression of the local wavelength of a surface plasmon polariton supported by two adjoining curved metal surfaces. Conference Name...diffraction imaging based on a process of adiabatic decompression of the local wavelength of a surface plasmon polariton supported by two adjoining curved

A computational genomics pipeline for prokaryotic sequencing projects.

PubMed

Kislyuk, Andrey O; Katz, Lee S; Agrawal, Sonia; Hagen, Matthew S; Conley, Andrew B; Jayaraman, Pushkala; Nelakuditi, Viswateja; Humphrey, Jay C; Sammons, Scott A; Govil, Dhwani; Mair, Raydel D; Tatti, Kathleen M; Tondella, Maria L; Harcourt, Brian H; Mayer, Leonard W; Jordan, I King

2010-08-01

New sequencing technologies have accelerated research on prokaryotic genomes and have made genome sequencing operations outside major genome sequencing centers routine. However, no off-the-shelf solution exists for the combined assembly, gene prediction, genome annotation and data presentation necessary to interpret sequencing data. The resulting requirement to invest significant resources into custom informatics support for genome sequencing projects remains a major impediment to the accessibility of high-throughput sequence data. We present a self-contained, automated high-throughput open source genome sequencing and computational genomics pipeline suitable for prokaryotic sequencing projects. The pipeline has been used at the Georgia Institute of Technology and the Centers for Disease Control and Prevention for the analysis of Neisseria meningitidis and Bordetella bronchiseptica genomes. The pipeline is capable of enhanced or manually assisted reference-based assembly using multiple assemblers and modes; gene predictor combining; and functional annotation of genes and gene products. Because every component of the pipeline is executed on a local machine with no need to access resources over the Internet, the pipeline is suitable for projects of a sensitive nature. Annotation of virulence-related features makes the pipeline particularly useful for projects working with pathogenic prokaryotes. The pipeline is licensed under the open-source GNU General Public License and available at the Georgia Tech Neisseria Base (http://nbase.biology.gatech.edu/). The pipeline is implemented with a combination of Perl, Bourne Shell and MySQL and is compatible with Linux and other Unix systems.

[Warning about risk of invasive infections in splenectomized patients. Experiences from University Hospital Brno, Czech Republic, in 2011].

PubMed

Polák, P; Freibergerová, M; Husa, P; Slesinger, P; Svoboda, R; Sťásek, J; Frola, L; Macháček, C

2012-09-01

Syndrome of fulminant sepsis in splenectomized (overwhelming postsplenectomy infection - OPSI) is feared and often fatal infectious complication in patients after splenectomy. The risk of syndrome of fulminant sepsis in splenectomized in these persons persists lifelong and doesn't diminish during the time. Etiologically, encapsulated bacterias like Streptococcus pneumoniae, Haemophilus influenzae group b and Neisseria meningitidis are involved. As the mortality of syndrome of fulminant sepsis in splenectomized is very high, it is indispensable to educate and vaccinate persons in risk. The authors present case reports of three splenectomized patients who were hospitalized for invasive pneumococcal infection in the University Hospital Brno, Czech Republic, in 2011.

Granzyme M and K release in human experimental endotoxemia.

PubMed

Wensink, Annette C; Wiewel, Maryse A; Jongeneel, Lieneke H; Boes, Marianne; van der Poll, Tom; Hack, C Erik; Bovenschen, Niels

2016-07-01

Granzymes are serine proteases involved in killing of tumor cells and virally infected cells. However, granzymes are also upregulated in blood under inflammatory conditions and contribute to cytokine release and processing. Here, we show that granzyme M (GrM) and to a lesser extent GrK are transiently elevated in the circulation following LPS administration in humans. GrM is released upon stimulation of whole blood with LPS or the gram-negative bacteria Escherichia coli BL21, Pseudomonas aeruginosa, and Neisseria meningitidis. GrK is only released upon stimulation with P. aeruginosa. Thus, GrM and GrK are differentially released in response to LPS and gram-negative bacteria. Copyright © 2016 Elsevier GmbH. All rights reserved.

Branimycins B and C, Antibiotics Produced by the Abyssal Actinobacterium Pseudonocardia carboxydivorans M-227.

PubMed

Braña, Alfredo F; Sarmiento-Vizcaíno, Aida; Pérez-Victoria, Ignacio; Otero, Luis; Fernández, Jonathan; Palacios, Juan José; Martín, Jesús; de la Cruz, Mercedes; Díaz, Caridad; Vicente, Francisca; Reyes, Fernando; García, Luis A; Blanco, Gloria

2017-02-24

Two new antibiotics, branimycins B (2) and C (3), were produced by fermentation of the abyssal actinobacterium Pseudonocardia carboxydivorans M-227, isolated from deep seawater of the Avilés submarine Canyon. Their structures were elucidated by HRMS and NMR analyses. These compounds exhibit antibacterial activities against a panel of Gram-positive bacteria, including Corynebacterium urealyticum, Clostridium perfringens, and Micrococcus luteus, and against the Gram-negative bacterium Neisseria meningitidis. Additionally, branimycin B displayed moderate antibacterial activity against other Gram-negative bacteria such as Bacteroides fragilis, Haemophilus influenzae, and Escherichia coli, and branimycin C against the Gram-positive Enterococcus faecalis and methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Local surface curvature analysis based on reflection estimation

NASA Astrophysics Data System (ADS)

Lu, Qinglin; Laligant, Olivier; Fauvet, Eric; Zakharova, Anastasia

2015-07-01

In this paper, we propose a novel reflection based method to estimate the local orientation of a specular surface. For a calibrated scene with a fixed light band, the band is reflected by the surface to the image plane of a camera. Then the local geometry between the surface and reflected band is estimated. Firstly, in order to find the relationship relying the object position, the object surface orientation and the band reflection, we study the fundamental theory of the geometry between a specular mirror surface and a band source. Then we extend our approach to the spherical surface with arbitrary curvature. Experiments are conducted with mirror surface and spherical surface. Results show that our method is able to obtain the local surface orientation merely by measuring the displacement and the form of the reflection.

The safety profile of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY).

PubMed

Rinderknecht, Stephen; Bryant, Kristina; Nolan, Terry; Pavia-Ruz, Noris; Doniz, Carlos Aranza; Weber, Miguel Angel Rodriguez; Cohen, Christopher; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline M

2012-03-01

The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8,500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12-15 mo of age in two primary vaccination and two fourth dose phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p value < 0.05). There were no statistically significant differences between groups in the incidences of SAEs, NOCDs, rash, or AEs leading to ER visits, with the exceptions of anemia and viral gastroenteritis, which occurred significantly less frequently in those receiving HibMenCY than those receiving commercially available Hib vaccines. In this pooled safety analysis, the safety profile of HibMenCY was similar to the safety profile of licensed monovalent Hib vaccines, despite the addition of meningococcal antigens. These studies are registered at www.clinicaltrials.gov NCT00345579 (primary vaccination study), NCT00345683 (fourth dose vaccination study) and NCT00289783 (primary and fourth dose vaccination studies).

Immunogenicity and safety of an investigational quadrivalent meningococcal ACWY tetanus toxoid conjugate vaccine in healthy adolescents and young adults 10 to 25 years of age.

PubMed

Baxter, Roger; Baine, Yaela; Ensor, Kathleen; Bianco, Veronique; Friedland, Leonard R; Miller, Jacqueline M

2011-03-01

An investigational quadrivalent Neisseria meningitidis serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) has been developed to expand available options for vaccination against invasive meningococcal disease. A total of 784 healthy adolescents and young adults 11 to 25 years of age were randomized (3:1) to receive a single dose of the MenACWY-TT vaccine or a licensed MenACWY diphtheria toxoid conjugate vaccine (MenACWY-DT). An additional nonrandomized group of 88 subjects 10 years of age received the MenACWY-TT vaccine only (MenACWY-TT/10). Immunogenicity was assessed 1 month postvaccination by human complement serum bactericidal assay (hSBA) for all serogroups. Solicited local and general symptoms were recorded for 8 days postvaccination and safety outcomes for 6 months. One month postvaccination, 81.9% to 96.1% of subjects had hSBA titers ≥ 1:8 in the MenACWY-TT group compared with 70.7% to 98.8% in the MenACWY-DT group. Exploratory analyses showed the proportion of subjects with hSBA titers ≥ 1:4 and ≥ 1:8 to be higher in the MenACWY-TT group than in the MenACWY-DT group for serogroups A, W-135, and Y. GMTs adjusted for age strata and baseline titer 1 month postvaccination were higher in the MenACWY-TT group than in the MenACWY-DT group for all 4 serogroups. The percentage of subjects reporting solicited local and general symptoms of any or Grade 3 severity or serious adverse events was similar between the 2 groups. Immune response and reactogenicity in the MenACWY-TT/10 group was similar to that in the MenACWY-TT group, except for higher hSBA-MenA GMTs in the MenACWY-TT/10 group. The investigational MenACWY-TT vaccine was immunogenic in adolescents and young adults, with an acceptable safety profile.

Differential response of surface temperature and atmospheric temperature to the biogeophysical effects of deforestation

NASA Astrophysics Data System (ADS)

Winckler, J.; Reick, C. H.; Lejeune, Q.; Pongratz, J.

2017-12-01

Deforestation influences temperature locally by changing the water, energy and momentum balance. While most observation-based studies and some modeling studies focused on the effects on surface temperature, other studies focused on the effects on near-surface air temperature. However, these two variables may respond differently to deforestation because changes in albedo and surface roughness may alter the land-atmosphere coupling and thus the vertical temperature distribution. Thus it is unclear whether it is possible to compare studies that assess the impacts of deforestation on these two different variables. Here, we analyze the biogeophysical effects of global-scale deforestation in the climate model MPI-ESM separately for surface temperature, 2m-air temperature and temperature the lowest atmospheric model layer. We investigate why the response of these variables differs by isolating the effects of only changing surface albedo and only changing surface roughness and by separating effects that are induced at the location of deforestation (local effects) from effects that are induced by advection and changes in circulation (nonlocal effects). Concerning surface temperature, we find that the local effects of deforestation lead to a global mean warming which is overcompensated by the nonlocal effects (up to 0.1K local warming versus -0.3K nonlocal cooling). The surface warming in the local effects is largely driven by the change in surface roughness while the cooling in the nonlocal effects is largely driven by the change in surface albedo. The nonlocal effects are largely consistent across surface temperature, 2m-air temperature, and the temperature of the lowest atmospheric layer. However, the local effects strongly differ across the three considered variables. The local effects are strong for surface temperature, but substantially weaker in the 2m-air temperature and largely absent in the lowest atmospheric layer. We conclude that studies focusing on the deforestation effects on surface temperature should not be compared to studies focusing on the effects on air temperature. While the local effects on surface temperature are useful for model evaluation, they might be less relevant for local adaptation and mitigation than previously thought because they might largely be absent in the atmosphere.

Costs of Neisseria meningitidis Group A Disease and Economic Impact of Vaccination in Burkina Faso

PubMed Central

Colombini, Anaïs; Trotter, Caroline; Madrid, Yvette; Karachaliou, Andromachi; Preziosi, Marie-Pierre

2015-01-01

Background. Five years since the successful introduction of MenAfriVac in a mass vaccination campaign targeting 1- to 29-year-olds in Burkina Faso, consideration must be given to the optimal strategies for sustaining population protection. This study aims to estimate the economic impact of a range of vaccination strategies in Burkina Faso. Methods. We performed a cost-of-illness study, comparing different vaccination scenarios in terms of costs to both households and health systems over a 26-year time horizon. These scenarios are (1) reactive vaccination campaign (baseline comparator); (2) preventive vaccination campaign; (3) routine immunization at 9 months; and (4) a combination of routine and an initial catchup campaign of children under 5. Costs were estimated from a literature review, which included unpublished programmatic documents and peer-reviewed publications. The future disease burden for each vaccination strategy was predicted using a dynamic transmission model of group A Neisseria meningitidis. Results. From 2010 to 2014, the total costs associated with the preventive campaign targeting 1- to 29-year-olds with MenAfriVac were similar to the estimated costs of the reactive vaccination strategy (approximately 10 million US dollars [USD]). Between 2015 and 2035, routine immunization with or without a catch-up campaign of 1- to 4-year-olds is cost saving compared with the reactive strategy, both with and without discounting costs and cases. Most of the savings are accrued from lower costs of case management and household costs resulting from a lower burden of disease. After the initial investment in the preventive strategy, 1 USD invested in the routine strategy saves an additional 1.3 USD compared to the reactive strategy. Conclusions. Prevention strategies using MenAfriVac will be significantly cost saving in Burkina Faso, both for the health system and for households, compared with the reactive strategy. This will protect households from catastrophic expenditures and increase the development capacity of the population. PMID:26553677

Meningococcal carriage prevalence in university students, 1824 years of age in Santiago, Chile.

PubMed

Rodriguez, P; Alvarez, I; Torres, M T; Diaz, J; Bertoglia, M P; Carcamo, M; Seoane, M; Araya, P; Russo, M; Santolaya, M E

2014-09-29

Neisseria meningitidis invasive disease is a major public health problem. Pharyngeal carriage is considered a prerequisite for invasive infection. Prevalence reaches 10% in general population and up to 30% in the 20-24 years age group. The aim of this study was to asses pharyngeal carriage prevalence in healthy subjects aged 18-24 years, and as secondary endpoints evaluate known risk factors, to identify serogroups and sequence in the isolated strains. Cross-sectional study in 500 healthy subjects; students from Universidad de Chile aged 18-24 years, Santiago, Chile, October 2012. Each subject underwent a risk factor survey prior to throat culture sampling. Samples were processed in one central Microbiology Laboratory of Hospital Luis Calvo Mackenna and serogrouping and sequencing was performed at Instituto de Salud Pública de Chile. We obtained throat samples from 500 healthy subjects, 20 (4%) positive for N. meningitidis. Of positive strains 20% were serogroup B, 15% W and the rest non groupable. The median age was 20 years, 50% were men. Of the risk factors evaluated, 24% were current smokers, 16% shared a room, 72% had kissed someone during the last month, 64% had gone to pub and 76% had consumed alcohol in the same period of time. Literatures meningococcal carriage prevalence reaches up to 30% in people aged 18-24 years. Prevalence in our study was 4%. Different interpretations could be given; one could be the absence of overcrowding in our students because of the lack of dorms in our scholar system and also the characteristics of our enrolled group. Our results suggest the necessity to extend the study to other age groups and to other cities, to better understand the Chilean reality, as well as others regions of America, considering that these results cannot be extrapolated to another countries. Copyright © 2014 Elsevier Ltd. All rights reserved.

Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States.

PubMed

Marshall, Gary S; Marchant, Colin D; Blatter, Mark; Friedland, Leonard R; Aris, Emmanuel; Miller, Jacqueline M

2011-02-01

An investigational combined Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY-TT) has been developed to protect infants from invasive disease caused by Hib and these meningococcal serogroups without adding injections to the immunization schedule. Incorporation of this novel vaccine into the US vaccination schedule will require demonstration of a lack of immunologic interference with other routine pediatric vaccines. This study assessed the immune response to 7-valent pneumococcal conjugate vaccine (PCV7) and combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine (DTaP-HepB-IPV) when separately co-administered with HibMenCY-TT as compared to a US-licensed H. influenzae type b tetanus toxoid conjugate vaccine (Hib-TT) at 2, 4, 6 (N=606) and 12-15 months of age (N=366). HibMenCY-TT was non-inferior to Hib-TT in terms of antibody responses to all Streptococcus pneumoniae serotypes contained in PCV7 and the diphtheria, tetanus, pertussis, hepatitis B and poliovirus antigens contained in DTaP-HepB-IPV one month after the third vaccine dose, and the anti-tetanus geometric mean antibody concentration (GMC) was significantly higher in the HibMenCY-TT group than in the Hib-TT group. In an exploratory analysis, no significant differences in the proportion of subjects with anti-pneumococcal antibody concentrations ≥0.2 µg/ml or anti-pneumococcal GMC were seen between the two groups after the fourth vaccine dose. A schedule of HibMenCY-TT given concomitantly with PCV7 and DTaP-HepB-IPV would be expected to protect infants against all of the targeted diseases.

Three-year antibody persistence and safety after a single dose of combined haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in Hib-primed toddlers.

PubMed

Booy, Robert; Richmond, Peter; Nolan, Terry; McVernon, Jodie; Marshall, Helen; Nissen, Michael; Reynolds, Graham; Ziegler, John B; Stoney, Tanya; Heron, Leon; Lambert, Stephen; Mesaros, Narcisa; Peddiraju, Kavitha; Miller, Jacqueline M

2013-02-01

Persistence of seroprotective bactericidal antibody titers is important for long-term protection against meningococcal serogroup C disease in young children. Antibody persistence values were determined in children up to 3 years after vaccination with a single dose of the combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine (Hib-MenC-TT; www.ClinicalTrials.gov: NCT00326118). The children had been randomized at ages 12-18 months to receive either 1 dose of Hib-MenC-TT (Hib-MenC group) or separately administered Hib-TT conjugate vaccine and MenC-CRM197 (MCC) vaccine (Hib plus MCC group). All children had been primed in infancy with a Hib vaccine. Antibodies against MenC were measured by a serum bactericidal assay using rabbit complement (rSBA-MenC) and antibodies against Hib polyribosylribitol phosphate were assessed by enzyme-linked immunosorbent assay. The rSBA-MenC titers ≥1:8 were demonstrated 3 years after vaccination in 64.2% and 53.2% of participants in the Hib-MenC group and in the Hib plus MCC group, respectively. Antipolyribosylribitol phosphate concentrations ≥0.15 µg/mL persisted in >98% of participants in both groups. The rSBA-MenC geometric mean titers and antipolyribosylribitol phosphate geometric mean concentrations remained higher 3 years after vaccination than before vaccination. No serious adverse events assessed by the investigator as being related to vaccination were reported. In this antibody persistence study of Hib-primed but MenC-naïve toddlers who received a single dose of Hib-MenC-TT, protective antibody levels against Hib and MenC were maintained in the majority of children 3 years after vaccination.

Neisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model.

PubMed

Borkowski, Julia; Li, Li; Steinmann, Ulrike; Quednau, Natascha; Stump-Guthier, Carolin; Weiss, Christel; Findeisen, Peter; Gretz, Norbert; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

2014-09-13

The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens. Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria. We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection. Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6 signaling and the transcriptional regulator IκBζ.

Incidence of bacteremia in infants and children with fever and petechiae.

PubMed

Mandl, K D; Stack, A M; Fleisher, G R

1997-09-01

We determined the incidence of serious invasive bacteremia caused by Neisseria meningitidis and other organisms in febrile infants and children with a petechial rash. Further, we studied the diagnostic value of laboratory and clinical finding in these patients. We conducted this prospective cohort study in the emergency department of an urban pediatric teaching hospital, during an 18-month period, and enrolled consecutive patients with temperature of 38 degrees C or higher and petechiae. Our measures included (1) laboratory tests (leukocyte count, coagulation profile, blood culture, and cerebrospinal fluid bacterial culture); (2) a questionnaire requesting clinical data including general appearance, number and location of petechiae, and presence or absence of purpura; and (3) a follow-up telephone survey documenting health status. A total of 411 patients were enrolled, with 57.7% between 3 and 36 months of age. Eight patients (1.9%) had bacteremia or clinical sepsis. Six had serious invasive bacteremia: N. meningitidis (two patients), group A streptococcus (one), or sepsis with negative culture results (three). Two had occult bacteremia caused by Streptococcus pneumoniae and no evidence of sepsis. No patient had a positive cerebrospinal fluid culture result. None of the 357 well-appearing patients (95% confidence interval: 0.0%, 1.0%) had serious invasive bacteremia. Fifty-three patients appeared ill, including all six with serious invasive bacteremia. Ill appearance of the child had a sensitivity of 1.00 (95% confidence interval: 0.60, 1.00), and a leukocyte count of 15,000 or greater, or of less than 5000, had a sensitivity of 1.0 (95% confidence interval: 0.53, 1.00) for detecting serious invasive bacteremia. All children with meningococcemia had purpura. Invasive bacteremia occurred less frequently in our study than in previous series and was identified by clinical criteria. Our data support the treatment of selected well-appearing children with fever and petechiae as outpatients.

Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years

PubMed Central

Comanducci, Maurizio; Amicizia, Daniela; Ansaldi, Filippo; Canepa, Paola; Orsi, Andrea; Icardi, Giancarlo; Rizzitelli, Emanuela; De Angelis, Gabriella; Bambini, Stefania; Moschioni, Monica; Comandi, Sara; Simmini, Isabella; Boccadifuoco, Giueseppe; Brunelli, Brunella; Giuliani, Marzia Monica; Pizza, Mariagrazia

2014-01-01

Neisseria meningitidis is an obligate human commensal that commonly colonizes the oropharyngeal mucosa. Carriage is age dependent and very common in young adults. The relationships between carriage and invasive disease are not completely understood. In this work, we performed a longitudinal carrier study in adolescents and young adults (173 subjects). Overall, 32 subjects (18.5%) had results that were positive for meningococcal carriage in at least one visit (average monthly carriage rate, 12.1%). Only five subjects tested positive at all four visits. All meningococcal isolates were characterized by molecular and serological techniques. Multilocus sequence typing, PorA typing, and sequencing of the 4CMenB vaccine antigens were used to assess strain diversity. The majority of positive subjects were colonized by capsule null (34.4%) and capsular group B strains (28.1%), accounting for 23.5% and 29.4% of the total number of isolates, respectively. The fHbp and nhba genes were present in all isolates, while the nadA gene was present in 5% of the isolates. The genetic variability of the 4CMenB vaccine antigens in this collection was relatively high compared with that of other disease-causing strain panels. Indications about the persistence of the carriage state were limited to the time span of the study. All strains isolated from the same subject were identical or cumulated minor changes over time. The expression levels and antigenicities of the 4CMenB vaccine antigens in each strain were analyzed by the meningococcal antigen typing system (MATS), which revealed that expression can change over time in the same individual. Future analysis of antigen variability and expression in carrier strains after the introduction of the MenB vaccine will allow for a definition of its impact on nasopharyngeal/oropharyngeal carriage. PMID:24648565

Geotemporal Analysis of Neisseria meningitidis Clones in the United States: 2000–2005

PubMed Central

Wiringa, Ann E.; Shutt, Kathleen A.; Marsh, Jane W.; Cohn, Amanda C.; Messonnier, Nancy E.; Zansky, Shelley M.; Petit, Susan; Farley, Monica M.; Gershman, Ken; Lynfield, Ruth; Reingold, Arthur; Schaffner, William; Thompson, Jamie; Brown, Shawn T.; Lee, Bruce Y.; Harrison, Lee H.

2013-01-01

Background The detection of meningococcal outbreaks relies on serogrouping and epidemiologic definitions. Advances in molecular epidemiology have improved the ability to distinguish unique Neisseria meningitidis strains, enabling the classification of isolates into clones. Around 98% of meningococcal cases in the United States are believed to be sporadic. Methods Meningococcal isolates from 9 Active Bacterial Core surveillance sites throughout the United States from 2000 through 2005 were classified according to serogroup, multilocus sequence typing, and outer membrane protein (porA, porB, and fetA) genotyping. Clones were defined as isolates that were indistinguishable according to this characterization. Case data were aggregated to the census tract level and all non-singleton clones were assessed for non-random spatial and temporal clustering using retrospective space-time analyses with a discrete Poisson probability model. Results Among 1,062 geocoded cases with available isolates, 438 unique clones were identified, 78 of which had ≥2 isolates. 702 cases were attributable to non-singleton clones, accounting for 66.0% of all geocoded cases. 32 statistically significant clusters comprised of 107 cases (10.1% of all geocoded cases) were identified. Clusters had the following attributes: included 2 to 11 cases; 1 day to 33 months duration; radius of 0 to 61.7 km; and attack rate of 0.7 to 57.8 cases per 100,000 population. Serogroups represented among the clusters were: B (n = 12 clusters, 45 cases), C (n = 11 clusters, 27 cases), and Y (n = 9 clusters, 35 cases); 20 clusters (62.5%) were caused by serogroups represented in meningococcal vaccines that are commercially available in the United States. Conclusions Around 10% of meningococcal disease cases in the U.S. could be assigned to a geotemporal cluster. Molecular characterization of isolates, combined with geotemporal analysis, is a useful tool for understanding the spread of virulent meningococcal clones and patterns of transmission in populations. PMID:24349182

Four-year antibody persistence and response to a booster dose of a pentavalent MenABCWY vaccine administered to healthy adolescents and young adults

PubMed Central

Sáez-Llorens, Xavier; Beltran-Rodriguez, Johnny; Novoa Pizarro, Jose M.; Mensi, Ilhem; Keshavan, Pavitra; Toneatto, Daniela

2018-01-01

ABSTRACT This open-label, multicenter extension study (NCT02451514) assessed persistence of Neisseria meningitidis serogroups ABCWY antibodies 4 years after primary vaccination. Adolescents and young adults who previously received 2 doses of MenABCWY+OMV (Group III), 1 dose of MenACWY-CRM (Group VI), or newly-recruited vaccine-naïve participants (Group VII) were administered 1 (Group III) or 2 doses (Groups VI and VII) of MenABCWY+OMV, 1 month apart. Immunogenicity was assessed by human serum bactericidal assay (hSBA). Safety and reactogenicity were also evaluated. Percentages of participants with hSBA titers ≥8 (serogroups ACWY), ≥5 (serogroup B) and hSBA geometric mean titers (GMTs) were evaluated in all 129 enrolled participants (Group III: 33; Group VI: 46; Group VII: 50). Anti-ACWY antibody concentrations waned over 4 years post-vaccination, but remained above pre-vaccination concentrations. Similarly, levels of antibodies against serogroup B test strains also waned over 4 years post-vaccination, but remained above pre-vaccination concentrations for some strains. MenABCWY+OMV booster induced a robust anamnestic anti-ACWY response in Group III and VI and a good response against serogroup B test strains (≥82%) in Group III. In serogroup B-naïve participants (Groups VI and VII), anti-B responses to 2 doses of MenABCWY+OMV were less homogenous and lower than in Group III. MenABCWY+OMV was reactogenic, but well-tolerated. No safety concerns were identified. These findings indicate that although antibodies against N. meningitidis serogroups ABCWY waned over 4 years post-vaccination, exposure to a MenABCWY+OMV booster dose elicits an anamnestic response in adolescents previously exposed to the same or another multivalent meningococcal vaccine. PMID:29601256

Use of cerebrospinal fluid and serum samples impregnated on FTATM Elute filter paper for the diagnosis of infections caused by Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae.

PubMed

Fukasawa, Lucila Okuyama; Gonçalves, Maria Gisele; Higa, Fábio Takenori; Castilho, Euclides Ayres; Ibarz-Pavón, Ana Belén; Sacchi, Claudio Tavares

2017-01-01

The lack of information regarding the burden of acute bacterial meningitis in Latin America leads to a reduction in the estimated incidence rates of the disease, and impairs public health decisions on the use and follow-up of preventive interventions, particularly, the evaluation of existing vaccination policies. The use of the real-time PCR in diagnostic routine procedures has resulted in a substantial increase in confirmed bacterial meningitis cases. However, in resource-poor countries, these assays are only available in reference laboratories. Sample transportation to these laboratories is a critical constraint, as it requires specialized, high cost courier services. To overcome this barrier we evaluated the use of FTATM Elute filter paper cards for the conservation and processing of samples under normal environmental conditions, as they would be when transported from remote and under-equipped healthcare facilities to the reference centers. A total of 401 samples received in 2015 as part of Sao Paulo's national surveillance for routine diagnosis were selected for this study. The sensitivity and specificity of real-time PCR were evaluated using fresh serum and cerebrospinal fluid (CSF) samples processed using our laboratory's standard DNA extraction, and processing the same samples after being dried and stored on FTATM card, and DNA extracted following the manufacturer's instructions. The sensitivities for detection of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from CSF dried and stored on FTATM cards were 98%, 92%, and 100%, respectively, and with serum samples were 73%, 88%, and 100%, respectively. When compared to our laboratory's standard methodology, results showed high concordance, with Kappa index ranges of 0.9877-1.00 for CSF, and 0.8004-1.00 for serum samples. The use of FTATM cards for CSF and serum conservation and transport represents a rapid, reliable, and cost-effective alternative that will allow obtaining valuable epidemiological information that would otherwise be lost.

An outbreak of serogroup C (ST-11) meningococcal disease in Tijuana, Mexico.

PubMed

Chacon-Cruz, Enrique; Espinosa-De Los Monteros, Luz Elena; Navarro-Alvarez, Samuel; Aranda-Lozano, Jose Luis; Volker-Soberanes, Maria Luisa; Rivas-Landeros, Rosa Maria; Alvelais-Arzamendi, Ariadna Annete; Vazquez, Julio Alberto

2014-05-01

Invasive meningococcal disease (IMD) has been reported to be endemic in children from Tijuana, Mexico and the risk of an outbreak was always a threat. To describe all clinical, epidemiological and microbiological features of a meningococcal outbreak that occurred in Tijuana, Mexico. All cases with IMD were admitted at different emergency departments within the city and diagnosed by culture and agglutination tests. Further restriction fragment length polymorphism pulse field gel electrophoresis (RFLP-PFGE) and multi locus sequence typing (MLST) were performed. All clinical and epidemiological characteristics and interventions were evaluated, as well as risk factors associated with mortality. From 30 January 2013 to 30 March 2013 there were 19 cases of IMD all caused by Neisseria meningitidis serogroup C. The median age was 16 years (2-47), with higher frequency among individuals at least 13 years old (73.7%). At admission, meningitis was the main clinical presentation (94.7%), followed by purpura (78.9%), septic shock (42.1%) and disseminated intravascular coagulation (DIC, 36.8%). Overall mortality was seven (36.8%). Variables associated with higher mortality were, at admission, presence of septic shock, DIC and thrombocytopenia less than 70,000. All 19 cases had no identifiable site or cluster as the source of the outbreak. RFLP-PFGE showed a discriminatory power for only one profile on all N. meningitidis strains analyzed and a clone ST-11 was identified in all strains. Public health interventions were continuous case reporting of all suspected cases of IMD, an increase in active surveillance in all hospitals, training of medical and laboratory personnel, massive and rapid chemoprophylaxis to all close contacts as indicated, and promotion of good health habits. An outbreak with high mortality of IMD occurred in Tijuana, Mexico. This event and evidence of endemicity should encourage health authorities to evaluate meningococcal vaccination in the region.

A local leaky-box model for the local stellar surface density-gas surface density-gas phase metallicity relation

NASA Astrophysics Data System (ADS)

Zhu, Guangtun Ben; Barrera-Ballesteros, Jorge K.; Heckman, Timothy M.; Zakamska, Nadia L.; Sánchez, Sebastian F.; Yan, Renbin; Brinkmann, Jonathan

2017-07-01

We revisit the relation between the stellar surface density, the gas surface density and the gas-phase metallicity of typical disc galaxies in the local Universe with the SDSS-IV/MaNGA survey, using the star formation rate surface density as an indicator for the gas surface density. We show that these three local parameters form a tight relationship, confirming previous works (e.g. by the PINGS and CALIFA surveys), but with a larger sample. We present a new local leaky-box model, assuming star-formation history and chemical evolution is localized except for outflowing materials. We derive closed-form solutions for the evolution of stellar surface density, gas surface density and gas-phase metallicity, and show that these parameters form a tight relation independent of initial gas density and time. We show that, with canonical values of model parameters, this predicted relation match the observed one well. In addition, we briefly describe a pathway to improving the current semi-analytic models of galaxy formation by incorporating the local leaky-box model in the cosmological context, which can potentially explain simultaneously multiple properties of Milky Way-type disc galaxies, such as the size growth and the global stellar mass-gas metallicity relation.

Hospital admission rates for meningitis and septicaemia caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in children in England over five decades: a population-based observational study.

PubMed

Martin, Natalie G; Sadarangani, Manish; Pollard, Andrew J; Goldacre, Michael J

2014-05-01

Infection with Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae causes substantial mortality and long-term morbidity in children. We know of no study to assess the long-term trends in hospital admission rates for meningitis and septicaemia caused by these pathogens in children in England. We aimed to do such a study using routinely reported data in England. In this population-based observational study, we used datasets that include routinely collected administrative statistics for hospital care: the Hospital In-Patient Enquiry (data for England from 1968 to 1985), the Hospital Episode Statistics dataset (data for England from 1989 onwards), and the Oxford record linkage study (data for Oxfordshire and surrounding areas from 1963 to 2011). We analysed annual age-specific and age-standardised admission rates in children younger than 15 years with H influenzae, meningococcal and pneumococcal meningitis, and septicaemia. We saw a reduction in hospital admission rates for childhood invasive bacterial disease after the introduction of conjugate vaccines against H influenzae, N meningitidis, and S pneumoniae in England. Annual incidence of H influenzae meningitis per 100,000 children decreased from 6·72 admissions (95% CI 6·18-7·26) in 1992 to 0·39 admissions (0·26-0·52) in 1994, after the introduction of routine H influenzae type b vaccination. We saw a small rise in admissions in the early 2000s, peaking at 1·24 admissions per 100,000 children (0·99-1·48) in 2003, which decreased to 0·28 per 100,000 children (0·17-0·39) by 2008 after the introduction of catch-up (2003) and routine (2006) booster programmes for young children. Meningococcal disease increased during the 1990s, reaching a peak in 1999, with 34·54 admissions (33·30-35·78) per 100,000 children. Hospital admissions decreased after the meningococcal serogroup C vaccine was introduced in 1999 and was 12·40 admissions (11·68-13·12) per 100,000 in 2011. Admissions for invasive pneumococcal disease increased from the 1990s reaching a peak in 2006 at 4·45 admissions for meningitis (95% CI 4·0-4·9) per 100,000 children and 2·81 admissions for septicaemia (2·45-3·17) per 100,000 children. A reduction in admissions occurred after the introduction of the pneumococcal conjugate vaccine in 2006: hospital admission rates in 2011 were 2·03 per 100,000 children for meningitis and 1·12 per 100,000 children for septicaemia. Vaccine-preventable invasive bacterial disease in children has decreased substantially in England in the past five decades, most notably with the advent of effective conjugate vaccines since the 1990s. Ongoing disease surveillance and continued development and implementation of vaccines against additional pneumococcal serotypes and serogroup B meningococcal disease are important. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

Robust feature detection and local classification for surfaces based on moment analysis.

PubMed

Clarenz, Ulrich; Rumpf, Martin; Telea, Alexandru

2004-01-01

The stable local classification of discrete surfaces with respect to features such as edges and corners or concave and convex regions, respectively, is as quite difficult as well as indispensable for many surface processing applications. Usually, the feature detection is done via a local curvature analysis. If concerned with large triangular and irregular grids, e.g., generated via a marching cube algorithm, the detectors are tedious to treat and a robust classification is hard to achieve. Here, a local classification method on surfaces is presented which avoids the evaluation of discretized curvature quantities. Moreover, it provides an indicator for smoothness of a given discrete surface and comes together with a built-in multiscale. The proposed classification tool is based on local zero and first moments on the discrete surface. The corresponding integral quantities are stable to compute and they give less noisy results compared to discrete curvature quantities. The stencil width for the integration of the moments turns out to be the scale parameter. Prospective surface processing applications are the segmentation on surfaces, surface comparison, and matching and surface modeling. Here, a method for feature preserving fairing of surfaces is discussed to underline the applicability of the presented approach.

Lactoferrin binding protein B – a bi-functional bacterial receptor protein

PubMed Central

Ostan, Nicholas K. H.; Yu, Rong-Hua; Ng, Dixon; Lai, Christine Chieh-Lin; Sarpe, Vladimir; Schriemer, David C.

2017-01-01

Lactoferrin binding protein B (LbpB) is a bi-lobed outer membrane-bound lipoprotein that comprises part of the lactoferrin (Lf) receptor complex in Neisseria meningitidis and other Gram-negative pathogens. Recent studies have demonstrated that LbpB plays a role in protecting the bacteria from cationic antimicrobial peptides due to large regions rich in anionic residues in the C-terminal lobe. Relative to its homolog, transferrin-binding protein B (TbpB), there currently is little evidence for its role in iron acquisition and relatively little structural and biophysical information on its interaction with Lf. In this study, a combination of crosslinking and deuterium exchange coupled to mass spectrometry, information-driven computational docking, bio-layer interferometry, and site-directed mutagenesis was used to probe LbpB:hLf complexes. The formation of a 1:1 complex of iron-loaded Lf and LbpB involves an interaction between the Lf C-lobe and LbpB N-lobe, comparable to TbpB, consistent with a potential role in iron acquisition. The Lf N-lobe is also capable of binding to negatively charged regions of the LbpB C-lobe and possibly other sites such that a variety of higher order complexes are formed. Our results are consistent with LbpB serving dual roles focused primarily on iron acquisition when exposed to limited levels of iron-loaded Lf on the mucosal surface and effectively binding apo Lf when exposed to high levels at sites of inflammation. PMID:28257520

Visualization of bacterial polysaccharides by scanning transmission electron microscopy.

PubMed

Wolanski, B S; McAleer, W J; Hilleman, M R

1983-04-01

Highly purified capsular polysaccharides of Neisseria meningitidis groups A, B, and C have been visualized by high resolution Scanning Transmission Electron Microscopy (STEM). Spheroidal macromolecules approximately 200 A in diameter are characteristic of the Meningococcus A and C polysaccharides whereas filaments that are 400-600 A in length are found in Meningococcus B polysaccharide preparations. Filaments are occasionally found associated with the spheroidal Meningococcus A and C polysaccharides and it is proposed that these structures are composed of a long (1-4 microns) filament or filaments that are arranged in spheroidal molecules or micelles of high molecular weight. The Meningococcus B polysaccharide, by contrast, is a short flexuous filament or strand of relatively low molecular weight. A relationship between morphology and antigenicity is proposed.

Molecular epidemiology of serogroup a meningitis in Moscow, 1969 to 1997.

PubMed Central

Achtman, M.; van der Ende, A.; Zhu, P.; Koroleva, I. S.; Kusecek, B.; Morelli, G.; Schuurman, I. G.; Brieske, N.; Zurth, K.; Kostyukova, N. N.; Platonov, A. E.

2001-01-01

Molecular analysis of 103 serogroup A Neisseria meningitidis strains isolated in Moscow from 1969 to 1997 showed that four independent clonal groupings were responsible for successive waves of meningococcal disease. An epidemic from 1969 to the mid-1970s was caused by genocloud 2 of subgroup III, possibly imported from China. Subsequent endemic disease through the early 1990s was caused by subgroup X and then by subgroup VI, which has also caused endemic disease elsewhere in eastern Europe. A 1996 epidemic was part of the pandemic spread from Asia of genocloud 8 of subgroup III. Recent genocloud 8 epidemic disease in Moscow may represent an early warning for spread of these bacteria to other countries in Europe. PMID:11384519

EEG source localization: Sensor density and head surface coverage.

PubMed

Song, Jasmine; Davey, Colin; Poulsen, Catherine; Luu, Phan; Turovets, Sergei; Anderson, Erik; Li, Kai; Tucker, Don

2015-12-30

The accuracy of EEG source localization depends on a sufficient sampling of the surface potential field, an accurate conducting volume estimation (head model), and a suitable and well-understood inverse technique. The goal of the present study is to examine the effect of sampling density and coverage on the ability to accurately localize sources, using common linear inverse weight techniques, at different depths. Several inverse methods are examined, using the popular head conductivity. Simulation studies were employed to examine the effect of spatial sampling of the potential field at the head surface, in terms of sensor density and coverage of the inferior and superior head regions. In addition, the effects of sensor density and coverage are investigated in the source localization of epileptiform EEG. Greater sensor density improves source localization accuracy. Moreover, across all sampling density and inverse methods, adding samples on the inferior surface improves the accuracy of source estimates at all depths. More accurate source localization of EEG data can be achieved with high spatial sampling of the head surface electrodes. The most accurate source localization is obtained when the voltage surface is densely sampled over both the superior and inferior surfaces. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Brain segmentation and the generation of cortical surfaces

NASA Technical Reports Server (NTRS)

Joshi, M.; Cui, J.; Doolittle, K.; Joshi, S.; Van Essen, D.; Wang, L.; Miller, M. I.

1999-01-01

This paper describes methods for white matter segmentation in brain images and the generation of cortical surfaces from the segmentations. We have developed a system that allows a user to start with a brain volume, obtained by modalities such as MRI or cryosection, and constructs a complete digital representation of the cortical surface. The methodology consists of three basic components: local parametric modeling and Bayesian segmentation; surface generation and local quadratic coordinate fitting; and surface editing. Segmentations are computed by parametrically fitting known density functions to the histogram of the image using the expectation maximization algorithm [DLR77]. The parametric fits are obtained locally rather than globally over the whole volume to overcome local variations in gray levels. To represent the boundary of the gray and white matter we use triangulated meshes generated using isosurface generation algorithms [GH95]. A complete system of local parametric quadratic charts [JWM+95] is superimposed on the triangulated graph to facilitate smoothing and geodesic curve tracking. Algorithms for surface editing include extraction of the largest closed surface. Results for several macaque brains are presented comparing automated and hand surface generation. Copyright 1999 Academic Press.

Comparisons of predicted steady-state levels in rooms with extended- and local-reaction bounding surfaces

NASA Astrophysics Data System (ADS)

Hodgson, Murray; Wareing, Andrew

2008-01-01

A combined beam-tracing and transfer-matrix model for predicting steady-state sound-pressure levels in rooms with multilayer bounding surfaces was used to compare the effect of extended- and local-reaction surfaces, and the accuracy of the local-reaction approximation. Three rooms—an office, a corridor and a workshop—with one or more multilayer test surfaces were considered. The test surfaces were a single-glass panel, a double-drywall panel, a carpeted floor, a suspended-acoustical ceiling, a double-steel panel, and glass fibre on a hard backing. Each test surface was modeled as of extended or of local reaction. Sound-pressure levels were predicted and compared to determine the significance of the surface-reaction assumption. The main conclusions were that the difference between modeling a room surface as of extended or of local reaction is not significant when the surface is a single plate or a single layer of material (solid or porous) with a hard backing. The difference is significant when the surface consists of multilayers of solid or porous material and includes a layer of fluid with a large thickness relative to the other layers. The results are partially explained by considering the surface-reflection coefficients at the first-reflection angles.

Local pH at the surface of hen egg white lysozyme

NASA Astrophysics Data System (ADS)

Otosu, Takuhiro; Kobayashi, Kaito; Yamaguchi, Shoichi

2018-02-01

The microenvironment at the surface of hen-egg-white lysozyme (HEWL) was examined by analyzing the change in pKa of fluorescein isothiocyanate (FITC) upon binding to the N-terminus of HEWL. The result showed that the local pH at the HEWL surface is higher than the bulk pH. Furthermore, the data showed that the difference between the local and bulk pH becomes larger with decreasing pH, suggesting HEWL repels more protons at lower pH. Because the local pH affects the protonation states of functional amino-acids at the protein surface, the results provide the fundamental insight into the microenvironment at the protein surface.

Economic evaluation of meningococcal serogroup B childhood vaccination in Ontario, Canada.

PubMed

Tu, Hong Anh T; Deeks, Shelley L; Morris, Shaun K; Strifler, Lisa; Crowcroft, Natasha; Jamieson, Frances B; Kwong, Jeffrey C; Coyte, Peter C; Krahn, Murray; Sander, Beate

2014-09-22

Invasive Neisseria meningitidis serogroup B (MenB) disease is a low incidence but severe infection (mean annual incidence 0.19/100,000/year, case fatality 11%, major long-term sequelae 10%) in Ontario, Canada. This study assesses the cost-effectiveness of a novel MenB vaccine from the Ontario healthcare payer perspective. A Markov cohort model of invasive MenB disease based on high quality local data and data from the literature was developed. A 4-dose vaccination schedule, 97% coverage, 90% effectiveness, 66% strain coverage, 10-year duration of protection, and vaccine cost of C$75/dose were assumed. A hypothetical Ontario birth cohort (n=150,000) was simulated to estimate expected lifetime health outcomes, quality-adjusted life years (QALYs), and costs, discounted at 5%. A MenB infant vaccination program is expected to prevent 4.6 invasive MenB disease cases over the lifetime of an Ontario birth cohort, equivalent to 10 QALYs gained. The estimated program cost of C$46.6 million per cohort (including C$318,383 for treatment of vaccine-associated adverse events) were not offset by healthcare cost savings of C$150,522 from preventing MenB cases, resulting in an incremental cost of C$4.76 million per QALY gained. Sensitivity analyses showed the findings to be robust. An infant MenB vaccination program significantly exceeds commonly used cost-effectiveness thresholds and thus is unlikely to be considered economically attractive in Ontario and comparable jurisdictions. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

A computational genomics pipeline for prokaryotic sequencing projects

PubMed Central

Kislyuk, Andrey O.; Katz, Lee S.; Agrawal, Sonia; Hagen, Matthew S.; Conley, Andrew B.; Jayaraman, Pushkala; Nelakuditi, Viswateja; Humphrey, Jay C.; Sammons, Scott A.; Govil, Dhwani; Mair, Raydel D.; Tatti, Kathleen M.; Tondella, Maria L.; Harcourt, Brian H.; Mayer, Leonard W.; Jordan, I. King

2010-01-01

Motivation: New sequencing technologies have accelerated research on prokaryotic genomes and have made genome sequencing operations outside major genome sequencing centers routine. However, no off-the-shelf solution exists for the combined assembly, gene prediction, genome annotation and data presentation necessary to interpret sequencing data. The resulting requirement to invest significant resources into custom informatics support for genome sequencing projects remains a major impediment to the accessibility of high-throughput sequence data. Results: We present a self-contained, automated high-throughput open source genome sequencing and computational genomics pipeline suitable for prokaryotic sequencing projects. The pipeline has been used at the Georgia Institute of Technology and the Centers for Disease Control and Prevention for the analysis of Neisseria meningitidis and Bordetella bronchiseptica genomes. The pipeline is capable of enhanced or manually assisted reference-based assembly using multiple assemblers and modes; gene predictor combining; and functional annotation of genes and gene products. Because every component of the pipeline is executed on a local machine with no need to access resources over the Internet, the pipeline is suitable for projects of a sensitive nature. Annotation of virulence-related features makes the pipeline particularly useful for projects working with pathogenic prokaryotes. Availability and implementation: The pipeline is licensed under the open-source GNU General Public License and available at the Georgia Tech Neisseria Base (http://nbase.biology.gatech.edu/). The pipeline is implemented with a combination of Perl, Bourne Shell and MySQL and is compatible with Linux and other Unix systems. Contact: king.jordan@biology.gatech.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20519285

Surface Wave Propagation on a Laterally Heterogeneous Earth

NASA Astrophysics Data System (ADS)

Tromp, Jeroen

1992-01-01

Love and Rayleigh waves propagating on the surface of the Earth exhibit path, phase and amplitude anomalies as a result of the lateral heterogeneity of the mantle. In the JWKB approximation, these anomalies can be determined by tracing surface wave trajectories, and calculating phase and amplitude anomalies along them. A time- or frequency -domain JWKB analysis yields local eigenfunctions, local dispersion relations, and conservation laws for the surface wave energy. The local dispersion relations determine the surface wave trajectories, and the energy equations determine the surface wave amplitudes. On an anisotrophic Earth model the local dispersion relation and the local vertical eigenfunctions depend explicitly on the direction of the local wavevector. Apart from the usual dynamical phase, which is the integral of the local wavevector along a raypath, there is an additional variation is phase. This additional phase, which is an analogue of the Berry phase in adiabatic quantum mechanics, vanishes in a waveguide with a local vertical two-fold symmetry axis or a local horizontal mirror plane. JWKB theory breaks down in the vicinity of caustics, where neighboring rays merge and the surface wave amplitude diverges. Based upon a potential representation of the surface wave field, a uniformly valid Maslov theory can be obtained. Surface wave trajectories are determined by a system of four ordinary differential equations which define a three-dimensional manifold in four-dimensional phase space (theta,phi,k_theta,k _phi), where theta is colatitude, phi is longitude, and k_theta and k _phi are the covariant components of the wavevector. There are no caustics in phase space; it is only when the rays in phase space are projected onto configuration space (theta,phi), the mixed spaces (k_theta,phi ) and (theta,k_phi), or onto momentum space (k_theta,k _phi), that caustics occur. The essential strategy is to employ a mixed or momentum space representation of the wavefield in the vicinity of a configuration space caustic.

Refined boundary conditions on the free surface of an elastic half-space taking into account non-local effects.

PubMed

Chebakov, R; Kaplunov, J; Rogerson, G A

2016-02-01

The dynamic response of a homogeneous half-space, with a traction-free surface, is considered within the framework of non-local elasticity. The focus is on the dominant effect of the boundary layer on overall behaviour. A typical wavelength is assumed to considerably exceed the associated internal lengthscale. The leading-order long-wave approximation is shown to coincide formally with the 'local' problem for a half-space with a vertical inhomogeneity localized near the surface. Subsequent asymptotic analysis of the inhomogeneity results in an explicit correction to the classical boundary conditions on the surface. The order of the correction is greater than the order of the better-known correction to the governing differential equations. The refined boundary conditions enable us to evaluate the interior solution outside a narrow boundary layer localized near the surface. As an illustration, the effect of non-local elastic phenomena on the Rayleigh wave speed is investigated.

The Negatively Charged Regions of Lactoferrin Binding Protein B, an Adaptation against Anti-Microbial Peptides

PubMed Central

Morgenthau, Ari; Beddek, Amanda; Schryvers, Anthony B.

2014-01-01

Lactoferrin binding protein B (LbpB) is a bi-lobed membrane bound lipoprotein that is part of the lactoferrin receptor complex in a variety of Gram-negative pathogens. Despite high sequence diversity among LbpBs from various strains and species, a cluster of negatively charged amino acids is invariably present in the protein’s C-terminal lobe in all species except Moraxella bovis. The function of LbpB in iron acquisition has yet to be experimentally demonstrated, whereas in vitro studies have shown that LbpB confers protection against lactoferricin, a short cationic antimicrobial peptide released from the N- terminus of lactoferrin. In this study we demonstrate that the negatively charged regions can be removed from the Neisseria meningitidis LbpB without compromising stability, and this results in the inability of LbpB to protect against the bactericidal effects of lactoferricin. The release of LbpB from the cell surface by the autotransporter NalP reduces the protection against lactoferricin in the in vitro killing assay, attributed to removal of LbpB during washing steps, but is unlikely to have a similar impact in vivo. The protective effect of the negatively charged polysaccharide capsule in the killing assay was less than the protection conferred by LbpB, suggesting that LbpB plays a major role in protection against cationic antimicrobial peptides in vivo. The selective release of LbpB by NalP has been proposed to be a mechanism for evading the adaptive immune response, by reducing the antibody binding to the cell surface, but may also provide insights into the primary function of LbpB in vivo. Although TbpB and LbpB have been shown to be major targets of the human immune response, the selective release of LbpB suggests that unlike TbpB, LbpB may not be essential for iron acquisition, but important for protection against cationic antimicrobial peptides. PMID:24465982

Mechanisms by Which Humidity Alters Ductility

DTIC Science & Technology

1982-06-01

Example Results and Discussion.,........,,,,,,,, .... 10 2.2 Effects of Ambient Water Vapor and Internal Hydrogen op Surface Microplasticity and Crack...Localized Microplastic Deformation of the Surface of Al 2219-T851,,. ,.. ... ,,. ... ,,* ,, .. ..... .. .... 55 4.2 Effects of Ambient Humidity and Internal...Hydrogen on Surface Local Microplastic Behavior ..... 00. ,00..... ..06...... 56 4.3 Relationship of Localized Plasticity to Crack Initiation and

Scaling law analysis of paraffin thin films on different surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dotto, M. E. R.; Camargo, S. S. Jr.

2010-01-15

The dynamics of paraffin deposit formation on different surfaces was analyzed based on scaling laws. Carbon-based films were deposited onto silicon (Si) and stainless steel substrates from methane (CH{sub 4}) gas using radio frequency plasma enhanced chemical vapor deposition. The different substrates were characterized with respect to their surface energy by contact angle measurements, surface roughness, and morphology. Paraffin thin films were obtained by the casting technique and were subsequently characterized by an atomic force microscope in noncontact mode. The results indicate that the morphology of paraffin deposits is strongly influenced by substrates used. Scaling laws analysis for coated substratesmore » present two distinct dynamics: a local roughness exponent ({alpha}{sub local}) associated to short-range surface correlations and a global roughness exponent ({alpha}{sub global}) associated to long-range surface correlations. The local dynamics is described by the Wolf-Villain model, and a global dynamics is described by the Kardar-Parisi-Zhang model. A local correlation length (L{sub local}) defines the transition between the local and global dynamics with L{sub local} approximately 700 nm in accordance with the spacing of planes measured from atomic force micrographs. For uncoated substrates, the growth dynamics is related to Edwards-Wilkinson model.« less

Local stability of galactic discs in modified dynamics

NASA Astrophysics Data System (ADS)

Shenavar, Hossein; Ghafourian, Neda

2018-04-01

The local stability of stellar and fluid discs, under a new modified dynamical model, is surveyed by using WKB approximation. The exact form of the modified Toomre criterion is derived for both types of systems and it is shown that the new model is, in all situations, more locally stable than Newtonian model. In addition, it has been proved that the central surface density of the galaxies plays an important role in the local stability in the sense that low surface brightness (LSB) galaxies are more stable than high surface brightness (HSBs). Furthermore, the growth rate in the new model is found to be lower than the Newtonian one. We found that, according to this model, the local instability is related to the ratio of surface density of the disc to a critical surface density Σcrit. We provide observational evidence to support this result based on star formation rate in HSBs and LSBs.

Contact angle and local wetting at contact line.

PubMed

Li, Ri; Shan, Yanguang

2012-11-06

This theoretical study was motivated by recent experiments and theoretical work that had suggested the dependence of the static contact angle on the local wetting at the triple-phase contact line. We revisit this topic because the static contact angle as a local wetting parameter is still not widely understood and clearly known. To further clarify the relationship of the static contact angle with wetting, two approaches are applied to derive a general equation for the static contact angle of a droplet on a composite surface composed of heterogeneous components. A global approach based on the free surface energy of a thermodynamic system containing the droplet and solid surface shows the static contact angle as a function of local surface chemistry and local wetting state at the contact line. A local approach, in which only local forces acting on the contact line are considered, results in the same equation. The fact that the local approach agrees with the global approach further demonstrates the static contact angle as a local wetting parameter. Additionally, the study also suggests that the wetting described by the Wenzel and Cassie equations is also the local wetting of the contact line rather than the global wetting of the droplet.

Manipulating and Monitoring On-Surface Biological Reactions by Light-Triggered Local pH Alterations.

PubMed

Peretz-Soroka, Hagit; Pevzner, Alexander; Davidi, Guy; Naddaka, Vladimir; Kwiat, Moria; Huppert, Dan; Patolsky, Fernando

2015-07-08

Significant research efforts have been dedicated to the integration of biological species with electronic elements to yield smart bioelectronic devices. The integration of DNA, proteins, and whole living cells and tissues with electronic devices has been developed into numerous intriguing applications. In particular, the quantitative detection of biological species and monitoring of biological processes are both critical to numerous areas of medical and life sciences. Nevertheless, most current approaches merely focus on the "monitoring" of chemical processes taking place on the sensing surfaces, and little efforts have been invested in the conception of sensitive devices that can simultaneously "control" and "monitor" chemical and biological reactions by the application of on-surface reversible stimuli. Here, we demonstrate the light-controlled fine modulation of surface pH by the use of photoactive molecularly modified nanomaterials. Through the use of nanowire-based FET devices, we showed the capability of modulating the on-surface pH, by intensity-controlled light stimulus. This allowed us simultaneously and locally to control and monitor pH-sensitive biological reactions on the nanodevices surfaces, such as the local activation and inhibition of proteolytic enzymatic processes, as well as dissociation of antigen-antibody binding interactions. The demonstrated capability of locally modulating the on-surface effective pH, by a light stimuli, may be further applied in the local control of on-surface DNA hybridization/dehybridization processes, activation or inhibition of living cells processes, local switching of cellular function, local photoactivation of neuronal networks with single cell resolution and so forth.

Local conductance: A means to extract polarization and depolarizing fields near domain walls in ferroelectrics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Douglas, A. M.; Kumar, A.; Gregg, J. M.

Conducting atomic force microscopy images of bulk semiconducting BaTiO{sub 3} surfaces show clear stripe domain contrast. High local conductance correlates with strong out-of-plane polarization (mapped independently using piezoresponse force microscopy), and current-voltage characteristics are consistent with dipole-induced alterations in Schottky barriers at the metallic tip-ferroelectric interface. Indeed, analyzing current-voltage data in terms of established Schottky barrier models allows relative variations in the surface polarization, and hence the local domain structure, to be determined. Fitting also reveals the signature of surface-related depolarizing fields concentrated near domain walls. Domain information obtained from mapping local conductance appears to be more surface-sensitive than thatmore » from piezoresponse force microscopy. In the right materials systems, local current mapping could therefore represent a useful complementary technique for evaluating polarization and local electric fields with nanoscale resolution.« less

Electron solvation and localization at interfaces

NASA Astrophysics Data System (ADS)

Harris, Charles B.; Szymanski, Paul; Garrett-Roe, Sean; Miller, Andre D.; Gaffney, Kelly J.; Liu, Simon H.; Bezel, Ilya

2003-12-01

Two-photon photoemission of thiolate/Ag(111), nitrile/Ag(111), and alcohol/Ag(111) interfaces elucidates electron solvation and localization in two dimensions. For low coverages of thiolates on Ag(111), the occupied (HOMO) and unoccupied (LUMO) electronic states of the sulfer-silver bond are localized due to the lattice gas structure of the adsorbate. As the coverage saturates and the adsorbate-adsorbate nearest neighbor distance decreases, the HOMO and LUMO delocalize across many adsorbate molecules. Alcohol- and nitrile-covered Ag(111) surfaces solvate excess image potential state (IPS) electrons. In the case of alcohol-covered surfaces, this solvation is due to a shift in the local workfunction of the surface. For two-monolayer coverages of nitriles/Ag(111), localization accompanies solvation of the IPS. The size of the localized electron can be estimated by Fourier transformation of the wavefunction from momentum- to position-space. The IPS electron localizes to 15 +/- 4 angstroms full-width at half maximum in the plane of the surface, i.e., to a single lattice site.

Immunochemical characterization of the "native" type III polysaccharide of group B Streptococcus

PubMed Central

1976-01-01

The type III polysaccharide of -roup B Streptococcus has been isolated and purified by a method that employs washing of intact cells at neutral pH. That the polysaccharide prepared by this procedure is the "native" type III antigen is suggested by its molecular size in excess of 10(6) daltons, its degradation by acid and heat treatment to a fragment with immunologic characteristics of the classical HCl antigen, and its type-specific serologic activity. The type III polysaccharide in native form contains sialic acid, galactose, glucose, glucosamine, heptose, and mannose. It is acidic in nature, is resistant to neuramindiase degradation, contains no O-acetyl groups, and does not share antigenic determinants with capsular type K1 antigen of Escherichia coli or Group B polysaccharide antigen of Neiserria meningitidis. PMID:55450

Bexsero® chronicle.

PubMed

Vernikos, George; Medini, Duccio

2014-10-01

Neisseria meningitidis causes globally 1·2 million invasive disease cases and 135,000 deaths per year, mostly in infants and adolescents. A century of traditional vaccinology had failed the fight against the serogroup B meningococcus (MenB), mostly prevalent in developed countries. Eighteen years after the publication of the first complete genome sequence from a living organism, thanks to an innovative genome-based approach named 'reverse vaccinology', the first broadly effective MenB vaccine was licensed for use by the European Medical Agency and other authorities, and is being implemented worldwide. Here we review this long and passionate journey, from the disease epidemiology to novel antigen discovery, from vaccine clinical development to public health impact: two decades of scientific and technological innovation to defeat one of the most sudden and devastating invasive diseases.

Size determination of bacterial capsular oligosaccharides used to prepare conjugate vaccines.

PubMed

Ravenscroft, N; Averani, G; Bartoloni, A; Berti, S; Bigio, M; Carinci, V; Costantino, P; D'Ascenzi, S; Giannozzi, A; Norelli, F; Pennatini, C; Proietti, D; Ceccarini, C; Cescutti, P

1999-07-16

We recently described the use of ion exchange chromatography for analysis and the industrial scale preparation of pools of oligosaccharides of intermediate chain length from polysaccharides of Haemophilus influenzae type b (Hib) and Neisseria meningitidis groups A and C. These negatively charged "sized" oligosaccharides are activated and conjugated to the carrier protein (CRM197) to prepare the corresponding glycoconjugate vaccines. Characterization and accurate determination of the degree of polymerization (DP) of the pool of oligosaccharides is essential for the consistent production of these conjugate vaccines. This paper describes the colorimetric assays used for determination of the average DP of the Hib and meningococcal oligosaccharides, and the qualification of these assays achieved by size characterization of the respective oligosaccharides by use of physicochemical methods, including liquid chromatography, mass spectrometry (ionspray) and NMR spectroscopy.

Future challenges in the elimination of bacterial meningitis.

PubMed

Bottomley, Matthew J; Serruto, Davide; Sáfadi, Marco Aurélio Palazzi; Klugman, Keith P

2012-05-30

Despite the widespread implementation of several effective vaccines over the past few decades, bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Group B Streptococcus (GBS) still results in unacceptably high levels of human mortality and morbidity. A residual disease burden due to bacterial meningitis is also apparent due to a number of persistent or emerging pathogens, including Mycobacterium tuberculosis, Escherichia coli, Staphylococcus aureus, Salmonella spp. and Streptococcus suis. Here, we review the current status of bacterial meningitis caused by these pathogens, highlighting how past and present vaccination programs have attempted to counter these pathogens. We discuss how improved pathogen surveillance, implementation of current vaccines, and development of novel vaccines may be expected to further reduce bacterial meningitis and related diseases in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Clinical evaluations of flomoxef in respiratory tract infections].

PubMed

Mikasa, K; Sawaki, M; Ako, H; Narita, N

1987-10-01

Flomoxef (FMOX, 6315-S), a new antibacterial drug, was administered to 9 cases with respiratory tract infections for a duration of 8 approximately 16 days at a daily dose of 2 g. Diagnosis of these patients were bronchopneumonia 5 cases, chronic bronchitis 3 cases and acute bronchitis 1 case. From transtracheal aspiration several organisms were isolated; Haemophilus influenzae was isolated in 3 cases, Streptococcus pneumoniae in 3 cases, H. influenzae plus Branhamella catarrhalis in 1 case, Streptococcus dysgalactiae plus Neisseria meningitidis in 1 case and Corynebacterium pseudodiphtheriticum in 1 case. The clinical efficacy was good in all 9 cases, the efficacy rate was 100%. All the bacteria were eliminated. Side effects were not observed. From these results, it appears that FMOX is a valuable drug in the treatment of respiratory tract infections.

Meningococcal vaccines: Current state and future outlook.

PubMed

Leca, M; Bornet, C; Montana, M; Curti, C; Vanelle, P

2015-06-01

Neisseria meningitidis infections are a major public health problem worldwide. Although conventional approaches have not led to development of a serogroup B meningococcal vaccine, a new technique based on genome sequencing has created new perspectives. Recently, a universal serogroup B meningococcal vaccine, Bexsero(®), was licensed in Europe, Australia and United States, following several clinical studies demonstrating its immunogenicity and safety. Availability of this vaccine could contribute positively to human health, by significantly reducing the incidence of meningococcal infections. However, unfavorable cost-effectiveness analysis means that routine vaccination is not currently recommended. Another serogroup meningococcal vaccine, Trumemba(®), was also recently licensed in United States. Like any drug, Bexsero(®) and Trumemba(®) will require close observation to assess their impact on meningococcal epidemiology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

CURVATURE-DRIVEN MOLECULAR FLOW ON MEMBRANE SURFACE*

PubMed Central

MIKUCKI, MICHAEL; ZHOU, Y. C.

2017-01-01

This work presents a mathematical model for the localization of multiple species of diffusion molecules on membrane surfaces. Morphological change of bilayer membrane in vivo is generally modulated by proteins. Most of these modulations are associated with the localization of related proteins in the crowded lipid environments. We start with the energetic description of the distributions of molecules on curved membrane surface, and define the spontaneous curvature of bilayer membrane as a function of the molecule concentrations on membrane surfaces. A drift-diffusion equation governs the gradient flow of the surface molecule concentrations. We recast the energetic formulation and the related governing equations by using an Eulerian phase field description to define membrane morphology. Computational simulations with the proposed mathematical model and related numerical techniques predict (i) the molecular localization on static membrane surfaces at locations with preferred mean curvatures, and (ii) the generation of preferred mean curvature which in turn drives the molecular localization. PMID:29056778

Binding ligand prediction for proteins using partial matching of local surface patches.

PubMed

Sael, Lee; Kihara, Daisuke

2010-01-01

Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group.

Binding Ligand Prediction for Proteins Using Partial Matching of Local Surface Patches

PubMed Central

Sael, Lee; Kihara, Daisuke

2010-01-01

Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group. PMID:21614188

Nanopillar Optical Antenna Avalanche Detectors

DTIC Science & Technology

2014-08-30

tuning and hybridization of the optical absorption via Surface Plasmon Polariton Bloch Waves (SPP-BWs) and Localized Surface Plasmon Resonances (LSPRs...of the optical absorption via Surface Plasmon Polariton Bloch Waves (SPP-BWs) and Localized Surface Plasmon Resonances (LSPRs) will be discussed...Surface Plasmon Polariton Bloch wave (SPP-BW) 36, 40. Also, resonant-field enhancement occurs in bounded metallic/dielectric structures that support

Localized heating on silicon field effect transistors: device fabrication and temperature measurements in fluid.

PubMed

Elibol, Oguz H; Reddy, Bobby; Nair, Pradeep R; Dorvel, Brian; Butler, Felice; Ahsan, Zahab S; Bergstrom, Donald E; Alam, Muhammad A; Bashir, Rashid

2009-10-07

We demonstrate electrically addressable localized heating in fluid at the dielectric surface of silicon-on-insulator field-effect transistors via radio-frequency Joule heating of mobile ions in the Debye layer. Measurement of fluid temperatures in close vicinity to surfaces poses a challenge due to the localized nature of the temperature profile. To address this, we developed a localized thermometry technique based on the fluorescence decay rate of covalently attached fluorophores to extract the temperature within 2 nm of any oxide surface. We demonstrate precise spatial control of voltage dependent temperature profiles on the transistor surfaces. Our results introduce a new dimension to present sensing systems by enabling dual purpose silicon transistor-heaters that serve both as field effect sensors as well as temperature controllers that could perform localized bio-chemical reactions in Lab on Chip applications.

Energetics of a two-phase model of lithospheric damage, shear localization and plate-boundary formation

NASA Astrophysics Data System (ADS)

Bercovici, David; Ricard, Yanick

2003-03-01

The two-phase theory for compaction and damage proposed by Bercovici et al. (2001a, J. Geophys. Res.,106, 8887-8906) employs a nonequilibrium relation between interfacial surface energy, pressure and viscous deformation, thereby providing a model for damage (void generation and microcracking) and a continuum description of weakening, failure and shear localization. Here we examine further variations of the model which consider (1) how interfacial surface energy, when averaged over the mixture, appears to be partitioned between phases; (2) how variability in deformational-work partitioning greatly facilitates localization; and (3) how damage and localization are manifested in heat output and bulk energy exchange. Microphysical considerations of molecular bonding and activation energy suggest that the apparent partitioning of surface energy between phases goes as the viscosity of the phases. When such partitioning is used in the two-phase theory, it captures the melt-compaction theory of McKenzie (1984, J. Petrol.,25, 713-765) exactly, as well as the void-damage theory proposed in a companion paper (Ricard & Bercovici, submitted). Calculations of 1-D shear localization with this variation of the theory still show at least three possible regimes of damage and localization: at low stress is weak localization with diffuse slowly evolving shear bands; at higher stress strong localization with narrow rapidly growing bands exists; and at yet higher shear stress it is possible for the system to undergo broadly distributed damage and no localization. However, the intensity of localization is strongly controlled by the variability of the deformational-work partitioning with dilation rate, represented by the parameter γ. For γ>> 1, extreme localization is allowed, with sharp profiles in porosity (weak zones), nearly discontinuous separation velocities and effectively singular dilation rates. Finally, the bulk heat output is examined for the 1-D system to discern how much deformational work is effectively stored as surface energy. In the high-stress, distributed-damage cases, heat output is reduced as more interfacial surface energy is created. Yet, in either the weak or strong localizing cases, the system always releases surface energy, regardless of the presence of damage or not, and thus slightly more heat is in fact released than energy is input through external work. Moreover, increased levels of damage (represented by the maximum work-partitioning f*) make the localizing system release surface energy faster as damage enhances phase separation and focusing of the porosity field, thus yielding more rapid loss of net interfacial surface area. However, when cases with different levels of damage are compared at similar stages of development (say, the peak porosity of the localization) it is apparent that increased damage causes smaller relative heat release and retards loss of net interfacial surface energy. The energetics and energy partitioning of this damage and shear-localization model are applied to estimating the energy costs of forming plate boundaries and generating plates from mantle convection.

Capturing strain localization behind a geosynthetic-reinforced soil wall

NASA Astrophysics Data System (ADS)

Lai, Timothy Y.; Borja, Ronaldo I.; Duvernay, Blaise G.; Meehan, Richard L.

2003-04-01

This paper presents the results of finite element (FE) analyses of shear strain localization that occurred in cohesionless soils supported by a geosynthetic-reinforced retaining wall. The innovative aspects of the analyses include capturing of the localized deformation and the accompanying collapse mechanism using a recently developed embedded strong discontinuity model. The case study analysed, reported in previous publications, consists of a 3.5-m tall, full-scale reinforced wall model deforming in plane strain and loaded by surcharge at the surface to failure. Results of the analysis suggest strain localization developing from the toe of the wall and propagating upward to the ground surface, forming a curved failure surface. This is in agreement with a well-documented failure mechanism experienced by the physical wall model showing internal failure surfaces developing behind the wall as a result of the surface loading. Important features of the analyses include mesh sensitivity studies and a comparison of the localization properties predicted by different pre-localization constitutive models, including a family of three-invariant elastoplastic constitutive models appropriate for frictional/dilatant materials. Results of the analysis demonstrate the potential of the enhanced FE method for capturing a collapse mechanism characterized by the presence of a failure, or slip, surface through earthen materials.

How Properties of Solid Surfaces Modulate the Nucleation of Gas Hydrate

PubMed Central

Bai, Dongsheng; Chen, Guangjin; Zhang, Xianren; Sum, Amadeu K.; Wang, Wenchuan

2015-01-01

Molecular dynamics simulations were performed for CO2 dissolved in water near silica surfaces to investigate how the hydrophilicity and crystallinity of solid surfaces modulate the local structure of adjacent molecules and the nucleation of CO2 hydrates. Our simulations reveal that the hydrophilicity of solid surfaces can change the local structure of water molecules and gas distribution near liquid-solid interfaces, and thus alter the mechanism and dynamics of gas hydrate nucleation. Interestingly, we find that hydrate nucleation tends to occur more easily on relatively less hydrophilic surfaces. Different from surface hydrophilicity, surface crystallinity shows a weak effect on the local structure of adjacent water molecules and on gas hydrate nucleation. At the initial stage of gas hydrate growth, however, the structuring of molecules induced by crystalline surfaces are more ordered than that induced by amorphous solid surfaces. PMID:26227239

The local work function: Concept and implications

NASA Astrophysics Data System (ADS)

Wandelt, K.

1997-02-01

The term 'local work function' is now widely applied. The present work discusses the common physical basis of 'photoemission of adsorbed xenon (PAX)' and 'two-photon photonemissionspectroscopy of image potential states' as local work function probes. New examples with bimetallic and defective surfaces are presented which demonstrate the capability of PAX measurements for the characterization of heterogeneous surfaces on an atomic scale. Finally, implications of the existence of short-range variations of the surface potential at surface steps are addressed. In particular, dynamical work function change measurements are a sensitive probe for the step-density at surfaces and, as such, a powerful in-situ method to monitor film growth.

Five-year Antibody Persistence and Safety After a Single Dose of Combined Haemophilus influenzae Type B Neisseria meningitidis Serogroup C-Tetanus Toxoid Conjugate Vaccine in Haemophilus influenzae Type B-primed Toddlers.

PubMed

Booy, Robert; Nolan, Terry; Reynolds, Graham; Richmond, Peter; Nissen, Michael; Marshall, Helen; Stoney, Tanya; Van Der Wielen, Marie; Kolhe, Devayani; Miller, Jacqueline M

2015-12-01

Antibody persistence is evaluated in healthy Australian children 4 and 5 years postvaccination with a single dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) compared with separately administered Hib-TT and MenC-CRM197 vaccines (Hib + MCC). This is another follow-up of a phase III, open, randomized, controlled study (NCT00326118), in which 433 Hib-primed but MenC naïve toddlers aged 12-18 months were randomized 3:1 to receive Hib-MenC-TT or Hib + MCC vaccines. Protection against (1) MenC was measured by serum bactericidal antibody assay using rabbit complement (rSBA) and (2) Hib was measured by enzyme-linked immunosorbent assay of antibodies to polyribosylribitol phosphate (anti-PRP). Study children were assessed for any potentially vaccine-related serious adverse events at each persistence study visit. The according-to-protocol cohorts for persistence at years 4 and 5 included 282 and 263 children, respectively. The percentages of children with rSBA-MenC titers ≥1:8 at years 4 and 5 were 12.5% and 19.0%, respectively, in the Hib-MenC group; and 12.3% and 25.0% in the Hib + MCC group. All children in each group had anti-PRP concentrations ≥0.15 μg/mL at year 5. Exploratory analyses suggested no potential differences between groups in rSBA-MenC or anti-PRP antibody persistence. No vaccine-related serious adverse events were reported. Antibody persistence was similar for years 4 and 5 after Hib-MenC-TT or Hib + MCC vaccination, with the majority of children retaining anti-PRP antibody concentrations ≥0.15 μg/mL at both timepoints. The percentage of children retaining rSBA-MenC titers ≥1:8 was low (≤25%), suggesting that a MenC booster dose may be warranted before adolescence.

Burden of bacterial meningitis in India: Preliminary data from a hospital based sentinel surveillance network.

PubMed

Jayaraman, Yuvaraj; Veeraraghavan, Balaji; Chethrapilly Purushothaman, Girish Kumar; Sukumar, Bharathy; Kangusamy, Boopathi; Nair Kapoor, Ambujam; Gupta, Nivedita; Mehendale, Sanjay Madhav

2018-01-01

Worldwide, acute bacterial meningitis is a major cause of high morbidity and mortality among under five children, particularly in settings where vaccination for H. influenzae type b, S. pneumoniae and N. meningitidis is yet to be introduced in the national immunization programs. Estimation of disease burden of bacterial meningitis associated with these pathogens can guide the policy makers to consider inclusion of these newer vaccines in the immunization programs. A network of hospital based sentinel surveillance was established to generate baseline data on the burden of bacterial meningitis among children aged less than 5 years in India and to provide a platform for impact assessment following introduction of the Pentavalent and Pneumococcal Conjugate Vaccines (PCV). During surveillance carried out in select hospitals across India in 2012-2013, information regarding demographics, immunization history, clinical history, treatment details and laboratory investigations viz. CSF biochemistry, culture, latex agglutination and PCR was collected from children aged 1 to 59 months admitted with suspected bacterial meningitis. A total of 3104 suspected meningitis cases were enrolled from 19,670 children admitted with fever at the surveillance hospitals. Of these, 257 cases were confirmed as cases of meningitis. They were due to S. pneumoniae (82.9%), H. influenzae type b (14.4%) and N. meningitidis (2.7%). Highest prevalence (55.3%) was observed among children 1 to 11 months. Antimicrobial susceptibility testing revealed considerable resistance among S. pneumoniae isolates against commonly used antibiotics such as cotrimoxazole, erythromycin, penicillin, and cefotaxime. More commonly prevalent serotypes of S. pneumoniae in circulation included 6B, 14, 6A and 19F. More than 90% of serotypes identified were covered by Pneumococcal Conjugate Vaccine 13. We observed that S. pneumoniae was the commonest cause of bacterial meningitis in hospitalized children under five years of age in India. Continued surveillance is expected to provide valuable information and trends in future, to take an informed decision on introduction of pneumococcal vaccination in Universal Immunization Programme in India and will also eventually help in post-vaccination impact evaluation.

Burden of bacterial meningitis in India: Preliminary data from a hospital based sentinel surveillance network

PubMed Central

Jayaraman, Yuvaraj; Veeraraghavan, Balaji; Chethrapilly Purushothaman, Girish Kumar; Sukumar, Bharathy; Kangusamy, Boopathi; Nair Kapoor, Ambujam; Gupta, Nivedita

2018-01-01

Background Worldwide, acute bacterial meningitis is a major cause of high morbidity and mortality among under five children, particularly in settings where vaccination for H. influenzae type b, S. pneumoniae and N. meningitidis is yet to be introduced in the national immunization programs. Estimation of disease burden of bacterial meningitis associated with these pathogens can guide the policy makers to consider inclusion of these newer vaccines in the immunization programs. A network of hospital based sentinel surveillance was established to generate baseline data on the burden of bacterial meningitis among children aged less than 5 years in India and to provide a platform for impact assessment following introduction of the Pentavalent and Pneumococcal Conjugate Vaccines (PCV). Methods During surveillance carried out in select hospitals across India in 2012–2013, information regarding demographics, immunization history, clinical history, treatment details and laboratory investigations viz. CSF biochemistry, culture, latex agglutination and PCR was collected from children aged 1 to 59 months admitted with suspected bacterial meningitis. Results A total of 3104 suspected meningitis cases were enrolled from 19,670 children admitted with fever at the surveillance hospitals. Of these, 257 cases were confirmed as cases of meningitis. They were due to S. pneumoniae (82.9%), H. influenzae type b (14.4%) and N. meningitidis (2.7%). Highest prevalence (55.3%) was observed among children 1 to 11 months. Antimicrobial susceptibility testing revealed considerable resistance among S. pneumoniae isolates against commonly used antibiotics such as cotrimoxazole, erythromycin, penicillin, and cefotaxime. More commonly prevalent serotypes of S. pneumoniae in circulation included 6B, 14, 6A and 19F. More than 90% of serotypes identified were covered by Pneumococcal Conjugate Vaccine 13. Conclusions We observed that S. pneumoniae was the commonest cause of bacterial meningitis in hospitalized children under five years of age in India. Continued surveillance is expected to provide valuable information and trends in future, to take an informed decision on introduction of pneumococcal vaccination in Universal Immunization Programme in India and will also eventually help in post-vaccination impact evaluation. PMID:29768458

A quantitative ELISA for antigen-specific IgG subclasses using equivalence dilutions of anti-kappa and anti-subclass specific secondary reagents. Application to the study of the murine immune response against the capsular polysaccharide of Neisseria meningitidis serogroup B.

PubMed

Colino, J; Diez, M; Outschoorn, I

1996-04-19

We have developed an enzyme-linked immunosorbent assay (ELISA) to measure murine antigen-specific IgG antibodies of defined subclass using precalibrated equivalence dilutions of anti-kappa (in the standard) and each anti-IgG subclass-specific polyclonal secondary antibody (in the test sample). The calibration of secondary reagents could be carried out easily with a set of monoclonal antibodies (MoAbs) specific for all IgG subclasses. These MoAbs do not require purification or standardization. In addition the MoAbs can be of different antigenic specificity. Once the equivalence dilutions have been determined, they can be applied in a quantitative ELISA using the same antigen in the standard and sample, and using only one IgG subclass standard for the determination of all the IgG subclasses. The method is easy to standardize for many antigenic systems. It is particularly useful when the only standard available is one standardized MoAb of the appropriate specificity, and it could be adapted to use with standard polyclonal antibodies having a known content of total antigen-specific IgG bearing kappa chains but unknown IgG subclass composition. The use of this method to quantitate IgG specific for the capsular polysaccharide of Neisseria meningitidis serogroup B (CpsB) gave highly reproducible measures with an interbatch CV of 5-6% similar for all IgG subclasses and low detection limits ranging from 0.3 ng/well for IgG3 to 0.8 ng/well for IgG2a. The IgG subclass response observed after immunization with live meningococci was mainly IgG2a (74%) and IgG2b (18%). Hyperimmunization modified this IgG distribution to one of mainly IgG3 (62%) and IgG1 (28%) which was maintained in the response to a single immunization 4 weeks later, possibly indicating the generation of resting B cells during continuous stimulation.

Detection of relatively penicillin G-resistant Neisseria meningitidis by disk susceptibility testing.

PubMed Central

Campos, J; Mendelman, P M; Sako, M U; Chaffin, D O; Smith, A L; Sáez-Nieto, J A

1987-01-01

Beginning in 1985, relatively penicillin G-resistant (Penr) meningococci which did not produce beta-lactamase were isolated from the blood and cerebrospinal fluid of patients in Spain. We identified 16 Penr (mean MIC, 0.3 microgram/ml; range, 0.1 to 0.7 microgram/ml) and 12 penicillin-susceptible (Pens; mean MIC, less than or equal to 0.06 microgram/ml) strains of Neisseria meningitidis by the agar dilution technique using an inoculum of 10(4) CFU and questioned which disk susceptibility test would best differentiate these two populations. We compared the disk susceptibility of these strains using disks containing 2 (P2) and 10 (P10) U of penicillin G, 2 (Am2) and 10 (Am10) micrograms of ampicillin, and 1 microgram of oxacillin (OX1). We also investigated susceptibility with disks containing 30 micrograms of each of cephalothin (CF30), cefoxitin (FOX30), cefuroxime (CXM30), and cefotaxime (CTX30) and 75 micrograms of cefoperazone (CFP75) and determined by cluster analysis any correlation with the zone diameters obtained with P2 disks. Using the P2 and AM2 disks (in contrast to the P10 and AM10 disks), we correctly differentiated all the Penr from Pens isolates. In addition, the zone diameters with the P2 disk gave the best correlation with the penicillin G MIC determinations. All 16 Penr strains and 3 of 12 Pens strains showed zone diameters of 6 mm around OX1 disks, limiting the usefulness of OX1 disks. The zone diameters obtained with CF30, CXM30, and OX1 disks correlated with those obtained with the P2 disk, which suggests that these antibiotics have similar effects on these strains. In contrast, the data obtained with FOX30, CTX30, and CFP75 disks did not cluster with those obtained with the P2 disk, which suggests that there was a difference in the bacterial target or reflects their greater activity. We conclude that the P2 disk tests more readily identify Penr meningococci than do the standard P10 disk tests. PMID:3124729

Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines

PubMed Central

Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela

2016-01-01

We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT00891176.) PMID:27145999

Temporal Changes in BEXSERO® Antigen Sequence Type Associated with Genetic Lineages of Neisseria meningitidis over a 15-Year Period in Western Australia

PubMed Central

Mowlaboccus, Shakeel; Perkins, Timothy T.; Smith, Helen; Sloots, Theo; Tozer, Sarah; Prempeh, Lydia-Jessica; Tay, Chin Yen; Peters, Fanny; Speers, David; Keil, Anthony D.; Kahler, Charlene M.

2016-01-01

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD). The BEXSERO® vaccine which is used to prevent serogroup B disease is composed of four sub-capsular protein antigens supplemented with an outer membrane vesicle. Since the sub-capsular protein antigens are variably expressed and antigenically variable amongst meningococcal isolates, vaccine coverage can be estimated by the meningococcal antigen typing system (MATS) which measures the propensity of the strain to be killed by vaccinated sera. Whole genome sequencing (WGS) which identifies the alleles of the antigens that may be recognised by the antibody response could represent, in future, an alternative estimate of coverage. In this study, WGS of 278 meningococcal isolates responsible for 62% of IMD in Western Australia from 2000–2014 were analysed for association of genetic lineage (sequence type [ST], clonal complex [cc]) with BEXSERO® antigen sequence type (BAST) and MATS to predict the annual vaccine coverage. A hyper-endemic period of IMD between 2000–05 was caused by cc41/44 with the major sequence type of ST-146 which was not predicted by MATS or BAST to be covered by the vaccine. An increase in serogroup diversity was observed between 2010–14 with the emergence of cc11 serogroup W in the adolescent population and cc23 serogroup Y in the elderly. BASTs were statistically associated with clonal complex although individual antigens underwent antigenic drift from the major type. BAST and MATS predicted an annual range of 44–91% vaccine coverage. Periods of low vaccine coverage in years post-2005 were not a result of the resurgence of cc41/44:ST-146 but were characterised by increased diversity of clonal complexes expressing BASTs which were not predicted by MATS to be covered by the vaccine. The driving force behind the diversity of the clonal complex and BAST during these periods of low vaccine coverage is unknown, but could be due to immune selection and inter-strain competition with carriage of non-disease causing meningococci. PMID:27355628

Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines.

PubMed

Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie

2016-07-01

We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT00891176.). Copyright © 2016 Tejedor et al.

Neisseria meningitidis Opc invasin binds to the sulphated tyrosines of activated vitronectin to attach to and invade human brain endothelial cells.

PubMed

Sa E Cunha, Claudia; Griffiths, Natalie J; Virji, Mumtaz

2010-05-20

The host vasculature is believed to constitute the principal route of dissemination of Neisseria meningitidis (Nm) throughout the body, resulting in septicaemia and meningitis in susceptible humans. In vitro, the Nm outer membrane protein Opc can enhance cellular entry and exit, utilising serum factors to anchor to endothelial integrins; but the mechanisms of binding to serum factors are poorly characterised. This study demonstrates that Nm Opc expressed in acapsulate as well as capsulate bacteria can increase human brain endothelial cell line (HBMEC) adhesion and entry by first binding to serum vitronectin and, to a lesser extent, fibronectin. This study also demonstrates that Opc binds preferentially to the activated form of human vitronectin, but not to native vitronectin unless the latter is treated to relax its closed conformation. The direct binding of vitronectin occurs at its Connecting Region (CR) requiring sulphated tyrosines Y(56) and Y(59). Accordingly, Opc/vitronectin interaction could be inhibited with a conformation-dependent monoclonal antibody 8E6 that targets the sulphotyrosines, and with synthetic sulphated (but not phosphorylated or unmodified) peptides spanning the vitronectin residues 43-68. Most importantly, the 26-mer sulphated peptide bearing the cell-binding domain (45)RGD(47) was sufficient for efficient meningococcal invasion of HBMECs. To our knowledge, this is the first study describing the binding of a bacterial adhesin to sulphated tyrosines of the host receptor. Our data also show that a single region of Opc is likely to interact with the sulphated regions of both vitronectin and of heparin. As such, in the absence of heparin, Opc-expressing Nm interact directly at the CR but when precoated with heparin, they bind via heparin to the heparin-binding domain of the activated vitronectin, although with a lower affinity than at the CR. Such redundancy suggests the importance of Opc/vitronectin interaction in meningococcal pathogenesis and may enable the bacterium to harness the benefits of the physiological processes in which the host effector molecule participates.

Use of cerebrospinal fluid and serum samples impregnated on FTATM Elute filter paper for the diagnosis of infections caused by Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae

PubMed Central

Gonçalves, Maria Gisele; Higa, Fábio Takenori; Castilho, Euclides Ayres; Ibarz-Pavón, Ana Belén; Sacchi, Claudio Tavares

2017-01-01

Background The lack of information regarding the burden of acute bacterial meningitis in Latin America leads to a reduction in the estimated incidence rates of the disease, and impairs public health decisions on the use and follow-up of preventive interventions, particularly, the evaluation of existing vaccination policies. The use of the real-time PCR in diagnostic routine procedures has resulted in a substantial increase in confirmed bacterial meningitis cases. However, in resource-poor countries, these assays are only available in reference laboratories. Sample transportation to these laboratories is a critical constraint, as it requires specialized, high cost courier services. To overcome this barrier we evaluated the use of FTATM Elute filter paper cards for the conservation and processing of samples under normal environmental conditions, as they would be when transported from remote and under-equipped healthcare facilities to the reference centers. A total of 401 samples received in 2015 as part of Sao Paulo’s national surveillance for routine diagnosis were selected for this study. Methods The sensitivity and specificity of real-time PCR were evaluated using fresh serum and cerebrospinal fluid (CSF) samples processed using our laboratory’s standard DNA extraction, and processing the same samples after being dried and stored on FTATM card, and DNA extracted following the manufacturer’s instructions. Results The sensitivities for detection of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from CSF dried and stored on FTATM cards were 98%, 92%, and 100%, respectively, and with serum samples were 73%, 88%, and 100%, respectively. When compared to our laboratory’s standard methodology, results showed high concordance, with Kappa index ranges of 0.9877–1.00 for CSF, and 0.8004–1.00 for serum samples. Conclusion The use of FTATM cards for CSF and serum conservation and transport represents a rapid, reliable, and cost-effective alternative that will allow obtaining valuable epidemiological information that would otherwise be lost. PMID:28235065

Local structural ordering in surface-confined liquid crystals

NASA Astrophysics Data System (ADS)

Śliwa, I.; Jeżewski, W.; Zakharov, A. V.

2017-06-01

The effect of the interplay between attractive nonlocal surface interactions and attractive pair long-range intermolecular couplings on molecular structures of liquid crystals confined in thin cells with flat solid surfaces has been studied. Extending the McMillan mean field theory to include finite systems, it has been shown that confining surfaces can induce complex orientational and translational ordering of molecules. Typically, local smectic A, nematic, and isotropic phases have been shown to coexist in certain temperature ranges, provided that confining cells are sufficiently thick, albeit finite. Due to the nonlocality of surface interactions, the spatial arrangement of these local phases can display, in general, an unexpected complexity along the surface normal direction. In particular, molecules located in the vicinity of surfaces can still be organized in smectic layers, even though nematic and/or isotropic order can simultaneously appear in the interior of cells. The resulting surface freezing of smectic layers has been confirmed to occur even for rather weak surface interactions. The surface interactions cannot, however, prevent smectic layers from melting relatively close to system boundaries, even when molecules are still arranged in layers within the central region of the system. The internal interfaces, separating individual liquid-crystal phases, are demonstrated here to form fronts of local finite-size transitions that move across cells under temperature changes. Although the complex molecular ordering in surface confined liquid-crystal systems can essentially be controlled by temperature variations, specific thermal properties of these systems, especially the nature of the local transitions, are argued to be strongly conditioned to the degree of molecular packing.

Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles.

PubMed

Asati, Atul; Santra, Santimukul; Kaittanis, Charalambos; Perez, J Manuel

2010-09-28

Cerium oxide nanoparticles (nanoceria) have shown great potential as antioxidant and radioprotective agents for applications in cancer therapy. Recently, various polymer-coated nanoceria preparations have been developed to improve their aqueous solubility and allow for surface functionalization of these nanoparticles. However, the interaction of polymer-coated nanoceria with cells, their uptake mechanism, and subcellular localization are poorly understood. Herein, we engineered polymer-coated cerium oxide nanoparticles with different surface charges (positive, negative, and neutral) and studied their internalization and toxicity in normal and cancer cell lines. The results showed that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g., cytoplasm and lysosomes) depending on the nanoparticle's surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticles' cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cells. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells. Taken together, these results indicate that the differential surface-charge-dependent localization of nanoceria in normal and cancer cells plays a critical role in the nanoparticles' toxicity profile.

Localized Heating on Silicon Field Effect Transistors: Device Fabrication and Temperature Measurements in Fluid

PubMed Central

Elibol, Oguz H.; Reddy, Bobby; Nair, Pradeep R.; Dorvel, Brian; Butler, Felice; Ahsan, Zahab; Bergstrom, Donald E.; Alam, Muhammad A.; Bashir, Rashid

2010-01-01

We demonstrate electrically addressable localized heating in fluid at the dielectric surface of silicon-on-insulator field-effect transistors via radio-frequency Joule heating of mobile ions in the Debye layer. Measurement of fluid temperatures in close vicinity to surfaces poses a challenge due to the localized nature of the temperature profile. To address this, we developed a localized thermometry technique based on the fluorescence decay rate of covalently attached fluorophores to extract the temperature within 2 nm of any oxide surface. We demonstrate precise spatial control of voltage dependent temperature profiles on the transistor surfaces. Our results introduce a new dimension to present sensing systems by enabling dual purpose silicon transistor-heaters that serve both as field effect sensors as well as temperature controllers that could perform localized bio-chemical reactions in Lab on Chip applications. PMID:19967115

LSAH: a fast and efficient local surface feature for point cloud registration

NASA Astrophysics Data System (ADS)

Lu, Rongrong; Zhu, Feng; Wu, Qingxiao; Kong, Yanzi

2018-04-01

Point cloud registration is a fundamental task in high level three dimensional applications. Noise, uneven point density and varying point cloud resolutions are the three main challenges for point cloud registration. In this paper, we design a robust and compact local surface descriptor called Local Surface Angles Histogram (LSAH) and propose an effectively coarse to fine algorithm for point cloud registration. The LSAH descriptor is formed by concatenating five normalized sub-histograms into one histogram. The five sub-histograms are created by accumulating a different type of angle from a local surface patch respectively. The experimental results show that our LSAH is more robust to uneven point density and point cloud resolutions than four state-of-the-art local descriptors in terms of feature matching. Moreover, we tested our LSAH based coarse to fine algorithm for point cloud registration. The experimental results demonstrate that our algorithm is robust and efficient as well.

Surface association and the MreB cytoskeleton regulate pilus production, localization and function in Pseudomonas aeruginosa.

PubMed

Cowles, Kimberly N; Gitai, Zemer

2010-06-01

Spatial organization of bacterial proteins influences many cellular processes, including division, chromosome segregation and motility. Virulence-associated proteins also localize to specific destinations within bacterial cells. However, the functions and mechanisms of virulence factor localization remain largely unknown. In this work, we demonstrate that polar assembly of the Pseudomonas aeruginosa PAO1 type IV pilus is regulated by surface association in a manner that affects gene transcription, protein levels and protein localization. We also uncover one mechanism for this regulation that acts through the actin homologue MreB. Inactivation of MreB leads to mislocalization of the pilus retraction ATPase PilT, mislocalization of the pili themselves and a reduction in motility. Furthermore, the role of MreB in polar localization of PilT is modulated by surface association, corroborating our results that environmental factors influence the regulation of pilus production. Specifically, MreB mediates both the initiation and maintenance of PilT localization when cells are grown in suspension but only affects the initiation of localization when cells are grown on a surface. Together, these results suggest that the bacterial cytoskeleton provides a mechanism for the polar localization of P. aeruginosa pili and demonstrate that protein localization may represent an important aspect of virulence factor regulation in bacterial pathogens.

Image Guidance in External Beam Accelerated Partial Breast Irradiation: Comparison of Surrogates for the Lumpectomy Cavity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasan, Yasmin; Kim, Leonard; Martinez, Alvaro

Purpose: To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. Methods and Materials: Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: (1) to bony anatomy, (2) to the center of mass (COM) of surgical clips, and (3) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs ({delta}COM{sub Bone}, {delta}COM{sub Clips}, and {delta}COM{sub Surface}) were determined. Smaller {delta}COMs were interpreted as bettermore » localizations. Correlation coefficients were calculated for {delta}COM vs. several variables. Results: The {delta}COM{sub Bone} (mean, 7 {+-} 2 [SD] mm) increased with breast volume (r = 0.4; p = 0.02) and distance from the chest wall (r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization ({delta}COM{sub Clips} < {delta}COM{sub Bone}) in 25 of 27 cases. Breast surface matching improved cavity localization ({delta}COM{sub Surface} < {delta}COM{sub Bone}) in 19 of 27 cases. Mean improvements ({delta}COM{sub Bone} - {delta}COM{sub ClipsorSurface}) were 4 {+-} 3 and 2 {+-} 4 mm, respectively. In terms of percentage of improvement ([{delta}COM{sub Bone} - {delta}COM{sub ClipsorSurface}]/{delta}COM{sub Bone}), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. Conclusions: Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable.« less

Method and system for optical figuring by imagewise heating of a solvent

DOEpatents

Rushford, Michael C.

2005-08-30

A method and system of imagewise etching the surface of a substrate, such as thin glass, in a parallel process. The substrate surface is placed in contact with an etchant solution which increases in etch rate with temperature. A local thermal gradient is then generated in each of a plurality of selected local regions of a boundary layer of the etchant solution to imagewise etch the substrate surface in a parallel process. In one embodiment, the local thermal gradient is a local heating gradient produced at selected addresses chosen from an indexed array of addresses. The activation of each of the selected addresses is independently controlled by a computer processor so as to imagewise etch the substrate surface at region-specific etch rates. Moreover, etching progress is preferably concurrently monitored in real time over the entire surface area by an interferometer so as to deterministically control the computer processor to image-wise figure the substrate surface where needed.

Surface localization of the nuclear receptor CAR in influenza A virus-infected cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Tadanobu; Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, CREST, JST, and COE Program in the 21st Century, Shizuoka 422-8526; Moriyama, Yusuke

Constitutive active/androstane receptor CAR is a member of the nuclear receptors which regulate transcription of xenobiotic metabolism enzymes. CAR is usually localized in the cytosol and nucleus. Here, we found that CAR was localized at the cell surface of influenza A virus (IAV)-infected cells. Additionally, we demonstrated that expression of a viral envelope glycoprotein, either hemagglutinin (HA) or neuraminidase (NA), but not viral nucleoprotein (NP), was responsible for this localization. This report is the first demonstration of CAR at the surface of tissue culture cells, and suggests that CAR may exert the IAV infection mechanism.

Localization of burn mark under an abnormal topography on MOSFET chip surface using liquid crystal and emission microscopy tools.

PubMed

Lau, C K; Sim, K S; Tso, C P

2011-01-01

This article focuses on the localization of burn mark in MOSFET and the scanning electron microscope (SEM) inspection on the defect location. When a suspect abnormal topography is shown on the die surface, further methods to pin-point the defect location is necessary. Fault localization analysis becomes important because an abnormal spot on the chip surface may and may not have a defect underneath it. The chip surface topography can change due to the catastrophic damage occurred at layers under the chip surface, but it could also be due to inconsistency during metal deposition in the wafer fabrication process. Two localization techniques, liquid crystal thermography and emission microscopy, were performed to confirm that the abnormal topography spot is the actual defect location. The tiny burn mark was surfaced by performing a surface decoration at the defect location using hot hydrochloric acid. SEM imaging, which has the high magnification and three-dimensional capabilities, was used to capture the images of the burn mark. Copyright © 2011 Wiley Periodicals, Inc.

Do the surface Fermi arcs in Weyl semimetals survive disorder?

NASA Astrophysics Data System (ADS)

Wilson, Justin H.; Pixley, J. H.; Huse, David A.; Refael, Gil; Das Sarma, S.

2018-06-01

We theoretically study the topological robustness of the surface physics induced by Weyl Fermi-arc surface states in the presence of short-ranged quenched disorder and surface-bulk hybridization. This is investigated with numerically exact calculations on a lattice model exhibiting Weyl Fermi arcs. We find that the Fermi-arc surface states, in addition to having a finite lifetime from disorder broadening, hybridize with nonperturbative bulk rare states making them no longer bound to the surface (i.e., they lose their purely surface spectral character). Thus, we provide strong numerical evidence that the Weyl Fermi arcs are not topologically protected from disorder. Nonetheless, the surface chiral velocity is robust and survives in the presence of strong disorder, persisting all the way to the Anderson-localized phase by forming localized current loops that live within the localization length of the surface. Thus, the Weyl semimetal is not topologically robust to the presence of disorder, but the surface chiral velocity is.

Alpha-fetoprotein detection by using a localized surface plasmon coupled fluorescence fiber-optic biosensor

NASA Astrophysics Data System (ADS)

Chang, Ying-Feng; Chen, Ran-Chou; Li, Ying-Chang; Yu, Chih-Jen; Hsieh, Bao-Yu; Chou, Chien

2007-11-01

Alpha-fetoprotein (AFP) detection by using a localized surface plasmon coupled fluorescence (LSPCF) fiber-optic biosensor is setup and experimentally demonstrated. It is based on gold nanoparticle (GNP) and coupled with localized surface plasmon wave on the surface of GNP. In this experiment, the fluorophores are labeled on anti-AFP which are bound to protein A conjugated GNP. Thus, LSPCF is excited with high efficiency in the near field of localized surface plasmon wave. Therefore, not only the sensitivity of LSPCF biosensor is enhanced but also the specific selectivity of AFP is improved. Experimentally, the ability of real time measurement in the range of AFP concentration from 0.1ng/ml to 100ng/ml was detected. To compare with conventional methods such as enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA), the LSPCF fiber-optic biosensor performs higher or comparable detection sensitivity, respectively.

Aging and the perception of local surface orientation from optical patterns of shading and specular highlights.

PubMed

Norman, J Farley; Wiesemann, Elizabeth Y

2007-01-01

Younger and older observers' ability to perceive local surface orientation from optical patterns of shading and specular highlights was investigated in two experiments. On each trial, the observers viewed a randomly generated, smoothly curved 3-D object and manipulated an adjustable gauge figure until its orientation matched that of a specific local region on the object's surface (cf. Koenderink, van Doom, & Kappers, 1992). The performance of both age groups was facilitated by the presence of binocular disparity (Experiment 1) and object rotation in depth (Experiment 2). Observers in both age groups were able to judge the surface tilt component of orientation more precisely than the slant component. Significant, but modest, effects of age were found in Experiment 1, but not in Experiment 2. The ability to perceive local surface orientation appears to be relatively well preserved with increasing age, at least through the age of 80.

Plasphonics: local hybridization of plasmons and phonons.

PubMed

Marty, Renaud; Mlayah, Adnen; Arbouet, Arnaud; Girard, Christian; Tripathy, Sudhiranjan

2013-02-25

We show that the interaction between localized surface plasmons sustained by a metallic nano-antenna and delocalized phonons lying at the surface of an heteropolar semiconductor can generate a new class of hybrid electromagnetic modes. These plasphonic modes are investigated using an analytical model completed by accurate Green dyadic numerical simulations. When surface plasmon and surface phonon frequencies match, the optical resonances exhibit a large Rabi splitting typical of strongly interacting two-level systems. Based on numerical simulations of the electric near-field maps, we investigate the nature of the plaphonic excitations. In particular, we point out a strong local field enhancement boosted by the phononic surface. This effect is interpreted in terms of light harvesting by the plasmonic antenna from the phononic surface. We thus introduce the concept of active phononic surfaces that may be exploited for far-infared optoelectronic devices and sensors.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection.

PubMed

Sanges, S; Wallet, F; Blondiaux, N; Theis, D; Vérin, I; Vachée, A; Dessein, R; Faure, K; Viget, N; Senneville, E; Leroy, O; Maury, F; Just, N; Poissy, J; Mathieu, D; Prévotat, A; Chenivesse, C; Scherpereel, A; Smith, G; Lopez, B; Rosain, J; Frémeaux-Bacchi, V; Hachulla, E; Hatron, P-Y; Bahuaud, M; Batteux, F; Launay, D; Labalette, M; Lefèvre, G

2017-08-01

Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Diagnostic accuracy of two multiplex real-time polymerase chain reaction assays for the diagnosis of meningitis in children in a resource-limited setting.

PubMed

Khumalo, Jermaine; Nicol, Mark; Hardie, Diana; Muloiwa, Rudzani; Mteshana, Phindile; Bamford, Colleen

2017-01-01

Accurate etiological diagnosis of meningitis is important, but difficult in resource-limited settings due to prior administration of antibiotics and lack of viral diagnostics. We aimed to develop and validate 2 real-time multiplex PCR (RT-PCR) assays for the detection of common causes of community-acquired bacterial and viral meningitis in South African children. We developed 2 multiplex RT- PCRs for detection of S. pneumoniae, N. meningitidis, H. influenzae, enteroviruses, mumps virus and herpes simplex virus. We tested residual CSF samples from children presenting to a local paediatric hospital over a one-year period, whose CSF showed an abnormal cell count. Results were compared with routine diagnostic tests and the final discharge diagnosis. We calculated accuracy of the bacterial RT-PCR assay compared to CSF culture and using World Health Organisation definitions of laboratory-confirmed bacterial meningitis. From 292 samples, bacterial DNA was detected in 12 (4.1%) and viral nucleic acids in 94 (32%). Compared to CSF culture, the sensitivity and specificity of the bacterial RT-PCR was 100% and 97.2% with complete agreement in organism identification. None of the cases positive by viral RT-PCR had a bacterial cause confirmed on CSF culture. Only 9/90 (10%) of patients diagnosed clinically as bacterial meningitis or partially treated bacterial meningitis tested positive with the bacterial RT-PCR. In this population the use of 2 multiplex RT-PCRs targeting 6 common pathogens gave promising results. If introduced into routine diagnostic testing, these multiplex RT-PCR assays would supplement other diagnostic tests, and have the potential to limit unnecessary antibiotic therapy and hospitalisation.

Diagnostic accuracy of two multiplex real-time polymerase chain reaction assays for the diagnosis of meningitis in children in a resource-limited setting

PubMed Central

Khumalo, Jermaine; Nicol, Mark; Hardie, Diana; Muloiwa, Rudzani; Mteshana, Phindile

2017-01-01

Introduction Accurate etiological diagnosis of meningitis is important, but difficult in resource-limited settings due to prior administration of antibiotics and lack of viral diagnostics. We aimed to develop and validate 2 real-time multiplex PCR (RT-PCR) assays for the detection of common causes of community-acquired bacterial and viral meningitis in South African children. Methods We developed 2 multiplex RT- PCRs for detection of S. pneumoniae, N. meningitidis, H. influenzae, enteroviruses, mumps virus and herpes simplex virus. We tested residual CSF samples from children presenting to a local paediatric hospital over a one-year period, whose CSF showed an abnormal cell count. Results were compared with routine diagnostic tests and the final discharge diagnosis. We calculated accuracy of the bacterial RT-PCR assay compared to CSF culture and using World Health Organisation definitions of laboratory-confirmed bacterial meningitis. Results From 292 samples, bacterial DNA was detected in 12 (4.1%) and viral nucleic acids in 94 (32%). Compared to CSF culture, the sensitivity and specificity of the bacterial RT-PCR was 100% and 97.2% with complete agreement in organism identification. None of the cases positive by viral RT-PCR had a bacterial cause confirmed on CSF culture. Only 9/90 (10%) of patients diagnosed clinically as bacterial meningitis or partially treated bacterial meningitis tested positive with the bacterial RT-PCR. Discussion In this population the use of 2 multiplex RT-PCRs targeting 6 common pathogens gave promising results. If introduced into routine diagnostic testing, these multiplex RT-PCR assays would supplement other diagnostic tests, and have the potential to limit unnecessary antibiotic therapy and hospitalisation. PMID:28346504

From voxel to curvature

NASA Astrophysics Data System (ADS)

Monga, Olivier; Ayache, Nicholas; Sander, Peter T.

1991-09-01

Modern medical image techniques, such as magnetic resonance image (MRI) or x-ray computed tomography provide three dimensional images of internal structures of the body, usually by means of a stack of tomographic images. The first stage in the automatic analysis of such data is 3-D edge detection1,2 which provides points corresponding to the boundaries of the surfaces forming the 3-D structure. The next stage is to characterize the local geometry of these surfaces in order to extract points or lines on which registration and/or tracking procedures can rely.3,4,5,6 This paper presents a pipeline of processes which define a hierarchical description of the second order differential characteristics of the surfaces. The focus is on the theoretical coherence of these levels of representation. Using uncertainty, a link is established between the edge detection and the local surface approximation by addressing the uncertainties inherent to edge detection in 2-D or 3-D images; and how to incorporate these uncertainties into the computation of local geometric models. In particular, calculate the uncertainty of edge location, direction, and magnitude for the 3-D Deriche operator is calculated.1,2 Statistical results are then used as a solid theoretical foundation on which to base subsequent computations, such as the determination of local surface curvature using local geometric models for surface segmentation. From the local fitting, for each edge point the mean and Gaussian curvature, principal curvatures and directions, curvature singularities, lines of curvature singularities, and covariance matrices defining the uncertainties are calculated. Experimental results for real data using two 3-D scanner images of the same organ taken at different positions demonstrate the stability of the mean and Gaussian curvatures. Experimental results for real data showing the determination of local curvature extremes of surfaces extracted from MR images are presented.

Sound Source Localization Using Non-Conformal Surface Sound Field Transformation Based on Spherical Harmonic Wave Decomposition

PubMed Central

Zhang, Lanyue; Ding, Dandan; Yang, Desen; Wang, Jia; Shi, Jie

2017-01-01

Spherical microphone arrays have been paid increasing attention for their ability to locate a sound source with arbitrary incident angle in three-dimensional space. Low-frequency sound sources are usually located by using spherical near-field acoustic holography. The reconstruction surface and holography surface are conformal surfaces in the conventional sound field transformation based on generalized Fourier transform. When the sound source is on the cylindrical surface, it is difficult to locate by using spherical surface conformal transform. The non-conformal sound field transformation by making a transfer matrix based on spherical harmonic wave decomposition is proposed in this paper, which can achieve the transformation of a spherical surface into a cylindrical surface by using spherical array data. The theoretical expressions of the proposed method are deduced, and the performance of the method is simulated. Moreover, the experiment of sound source localization by using a spherical array with randomly and uniformly distributed elements is carried out. Results show that the non-conformal surface sound field transformation from a spherical surface to a cylindrical surface is realized by using the proposed method. The localization deviation is around 0.01 m, and the resolution is around 0.3 m. The application of the spherical array is extended, and the localization ability of the spherical array is improved. PMID:28489065

Detoxified Endotoxin Vaccine (J5dLPS/OMP) Protects Mice Against Lethal Respiratory Challenge with Francisella tularensis SchuS4

PubMed Central

Gregory, Stephen H.; Chen, Wilbur H.; Mott, Stephanie; Palardy, John E.; Parejo, Nicholas A.; Heninger, Sara; Anderson, Christine A.; Artenstein, Andrew W.; Opal, Steven M.; Cross, Alan S.

2010-01-01

Francisella tularensis is a category A select agent. J5dLPS/OMP is a novel vaccine construct consisting of detoxified, O-polysaccharide side chain-deficient, lipopolysaccharide non-covalently complexed with the outer membrane protein of N. meningitidis group B. Immunization elicits hightiter polyclonal antibodies specific for the highly-conserved epitopes expressed within the glycolipid core that constitutes gram-negative bacteria (e.g., F. tularensis). Mice immunized intranasally with J5dLPS/OMP exhibited protective immunity to intratracheal challenge with the live vaccine strain, as well as the highly-virulent SchuS4 strain, of F. tularensis. The efficacy of J5dLPS/OMP vaccine suggests its potential utility in immunizing the general population against several different gram-negative select agents concurrently. PMID:20170768

Consensus recommendation for meningococcal disease prevention for Hajj and Umra pilgrimage/travel medicine.

PubMed

Shibl, A; Tufenkeji, H; Khalil, M; Memish, Z

2013-04-01

The Islamic Hajj to Makkah (Mecca) has been associated with outbreaks of invasive meningococcal disease and the global spread of Neisseria meningitidis serogroup W-135. For Hajj pilgrims the quadrivalent vaccination against serogroups A, C, W-135 and Y is a mandatory requirement. Novel conjugate vaccines may provide benefits for the community by reduction of carriage. With the introduction of the new generation of quadrivalent meningococcal conjugate vaccines (Menveo, Menactra, and others pending license) and their recent implementation in Saudi Arabia, experts from 11 countries in the Middle East region met at a Meningococcal Leadership Forum (MLF), in Dubai in May 2010 to exchange opinions on meningococcal disease and prevention strategies. These experts discussed the importance of introducing conjugate vaccines for pilgrims and travellers, and elaborated a consensus recommendation to support healthcare professionals and decision-makers.

Protection of rhesus macaques against inhalational anthrax with a Bacillus anthracis capsule conjugate vaccine.

PubMed

Chabot, Donald J; Ribot, Wilson J; Joyce, Joseph; Cook, James; Hepler, Robert; Nahas, Debbie; Chua, Jennifer; Friedlander, Arthur M

2016-07-25

The efficacy of currently licensed anthrax vaccines is largely attributable to a single Bacillus anthracis immunogen, protective antigen. To broaden protection against possible strains resistant to protective antigen-based vaccines, we previously developed a vaccine in which the anthrax polyglutamic acid capsule was covalently conjugated to the outer membrane protein complex of Neisseria meningitidis serotype B and demonstrated that two doses of 2.5μg of this vaccine conferred partial protection of rhesus macaques against inhalational anthrax . Here, we demonstrate complete protection of rhesus macaques against inhalational anthrax with a higher 50μg dose of the same capsule conjugate vaccine. These results indicate that B. anthracis capsule is a highly effective vaccine component that should be considered for incorporation in future generation anthrax vaccines. Published by Elsevier Ltd.

Numerical analysis of the effect of surface roughness on mechanical fields in polycrystalline aggregates

NASA Astrophysics Data System (ADS)

Guilhem, Yoann; Basseville, Stéphanie; Curtit, François; Stéphan, Jean-Michel; Cailletaud, Georges

2018-06-01

This paper is dedicated to the study of the influence of surface roughness on local stress and strain fields in polycrystalline aggregates. Finite element computations are performed with a crystal plasticity model on a 316L stainless steel polycrystalline material element with different roughness states on its free surface. The subsequent analysis of the plastic strain localization patterns shows that surface roughness strongly affects the plastic strain localization induced by crystallography. Nevertheless, this effect mainly takes place at the surface and vanishes under the first layer of grains, which implies the existence of a critical perturbed depth. A statistical analysis based on the plastic strain distribution obtained for different roughness levels provides a simple rule to define the size of the affected zone depending on the rough surface parameters.

Local mass and energy transports in evaporation processes from a vapor-liquid interface in a slit pore based on molecular dynamics

NASA Astrophysics Data System (ADS)

Fujiwara, K.; Shibahara, M.

2018-02-01

Molecular evaporation processes from a vapor-liquid interface formed in a slit-like pore were examined based on the classical molecular dynamics method, in order to elucidate a molecular mechanism of local mass and energy transports in a slit. The calculation system consisted of monatomic molecules and atoms which interact through the 12-6 Lennard-Jones potential. At first, a liquid was situated in a slit with a vapor-liquid interface, and instantaneous amounts of the mass and energy fluxes defined locally in the slit were obtained in two dimensions to reveal local fluctuation properties of the fluid in equilibrium states. Then, imposing a temperature gradient in the calculation system, non-equilibrium evaporation processes in the slit were investigated in details based on the local mass and energy fluxes. In this study, we focused on the fluid which is in the vicinity of the solid surface and in contact with the vapor phase. In the non-equilibrium evaporation processes, the results revealed that the local energy transport mechanism in the vicinity of the solid surface is different from that of the vapor phase, especially in the case of the relatively strong fluid-solid interaction. The results also revealed that the local mass transport in the vicinity of the solid surface can be interpreted based on the mechanism of the local energy transport, and the mechanism provides valuable information about pictures of the evaporation phenomena especially in the vicinity of the hydrophilic surfaces. It suggests that evaluating and changing this mechanism of the local energy transport are necessary to control the local mass flux more precisely in the vicinity of the solid surface.

The perception of three-dimensionality across continuous surfaces

NASA Technical Reports Server (NTRS)

Stevens, Kent A.

1989-01-01

The apparent three-dimensionality of a viewed surface presumably corresponds to several internal preceptual quantities, such as surface curvature, local surface orientation, and depth. These quantities are mathematically related for points within the silhouette bounds of a smooth, continuous surface. For instance, surface curvature is related to the rate of change of local surface orientation, and surface orientation is related to the local gradient of distance. It is not clear to what extent these 3D quantities are determined directly from image information rather than indirectly from mathematically related forms, by differentiation or by integration within boundary constraints. An open empirical question, for example, is to what extent surface curvature is perceived directly, and to what extent it is quantitative rather than qualitative. In addition to surface orientation and curvature, one derives an impression of depth, i.e., variations in apparent egocentric distance. A static orthographic image is essentially devoid of depth information, and any quantitative depth impression must be inferred from surface orientation and other sources. Such conversion of orientation to depth does appear to occur, and even to prevail over stereoscopic depth information under some circumstances.

Local-Scale Simulations of Nucleate Boiling on Micrometer Featured Surfaces: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sitaraman, Hariswaran; Moreno, Gilberto; Narumanchi, Sreekant V

2017-08-03

A high-fidelity computational fluid dynamics (CFD)-based model for bubble nucleation of the refrigerant HFE7100 on micrometer-featured surfaces is presented in this work. The single-fluid incompressible Navier-Stokes equations, along with energy transport and natural convection effects are solved on a featured surface resolved grid. An a priori cavity detection method is employed to convert raw profilometer data of a surface into well-defined cavities. The cavity information and surface morphology are represented in the CFD model by geometric mesh deformations. Surface morphology is observed to initiate buoyancy-driven convection in the liquid phase, which in turn results in faster nucleation of cavities. Simulationsmore » pertaining to a generic rough surface show a trend where smaller size cavities nucleate with higher wall superheat. This local-scale model will serve as a self-consistent connection to larger device scale continuum models where local feature representation is not possible.« less

Local-Scale Simulations of Nucleate Boiling on Micrometer-Featured Surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sitaraman, Hariswaran; Moreno, Gilberto; Narumanchi, Sreekant V

2017-07-12

A high-fidelity computational fluid dynamics (CFD)-based model for bubble nucleation of the refrigerant HFE7100 on micrometer-featured surfaces is presented in this work. The single-fluid incompressible Navier-Stokes equations, along with energy transport and natural convection effects are solved on a featured surface resolved grid. An a priori cavity detection method is employed to convert raw profilometer data of a surface into well-defined cavities. The cavity information and surface morphology are represented in the CFD model by geometric mesh deformations. Surface morphology is observed to initiate buoyancy-driven convection in the liquid phase, which in turn results in faster nucleation of cavities. Simulationsmore » pertaining to a generic rough surface show a trend where smaller size cavities nucleate with higher wall superheat. This local-scale model will serve as a self-consistent connection to larger device scale continuum models where local feature representation is not possible.« less

Localization through surface folding in solid foams under compression.

PubMed

Reis, P M; Corson, F; Boudaoud, A; Roman, B

2009-07-24

We report a combined experimental and theoretical study of the compression of a solid foam coated with a thin elastic film. Past a critical compression threshold, a pattern of localized folds emerges with a characteristic size that is imposed by an instability of the thin surface film. We perform optical surface measurements of the statistical properties of these localization zones and find that they are characterized by robust exponential tails in the strain distributions. Following a hybrid continuum and statistical approach, we develop a theory that accurately describes the nucleation and length scale of these structures and predicts the characteristic strains associated with the localized regions.

Synthesis methods of gold nanoparticles for Localized Surface Plasmon Resonance (LSPR) sensor applications

NASA Astrophysics Data System (ADS)

Diyanah Samsuri, Nurul; Maisarah Mukhtar, Wan; Rashid, Affa Rozana Abdul; Dasuki, Karsono Ahmad; Awangku Yussuf, Awangku Abdul Rahman Hj.

2017-11-01

Gold nanoparticles (GNPs) have been known as an excellent characteristic for Local Surface Plasmon Resonance (LSPR) sensors due to their sensitive spectral response to the local environment of the nanoparticle surface and ease of monitoring the light signal due to their strong scattering or absorption. Prior the technologies, GNPs based LSPR has been commercialized and have become a central tool for characterizing and quantifying in various field. In this review, we presented a brief introduction on the history of surface plasmon, the theory behind the surface plasmon resonance (SPR) and the principles of LSPR. We also reported on the synthetization as well of the properties of the GNPs and the applications in current LSPR sensors.

Evaluate methodology to determine localized roughness.

DOT National Transportation Integrated Search

2016-03-01

The Texas Department of Transportation implements a smoothness specification based on inertial profile : measurements. This specification includes a localized roughness provision to locate defects on the final : surface based on measured surface prof...

An inquiry into the cirrus-cloud thermostat effect for tropical sea surface temperature

NASA Technical Reports Server (NTRS)

Lau, K.-M.; Sui, C.-H.; Chou, M.-D.; Tao, W.-K.

1994-01-01

In this paper, we investigate the relative importance of local vs remote control on cloud radiative forcing using a cumulus ensemble model. It is found that cloud and surface radiation forcings are much more sensitive to the mean vertical motion assoicated with large scale tropical circulation than to the local SST (sea surface temperature). When the local SST is increased with the mean vertical motion held constant, increased surface latent and sensible heat flux associated with enhanced moisture recycling is found to be the primary mechanism for cooling the ocean surface. Large changes in surface shortwave fluxes are related to changes in cloudiness induced by changes in the large scale circulation. These results are consistent with a number of earlier empirical studies, which raised concerns regarding the validity of the cirrus-thermostat hypothesis (Ramanathan and Collins, 1991). It is argued that for a better understanding of cloud feedback, both local and remote controls need to be considered and that a cumulus ensemble model is a powerful tool that should be explored for such purpose.

Local shape of pictorial relief

PubMed Central

Koenderink, Jan; van Doorn, Andrea; Wagemans, Johan

2014-01-01

How is pictorial relief represented in visual awareness? Certainly not as a “depth map,” but perhaps as a map of local surface attitudes (Koenderink & van Doorn, 1995). Here we consider the possibility that observers might instead, or concurrently, represent local surface shape, a geometrical invariant with respect to motions. Observers judge local surface shape, in a picture of a piece of sculpture, on a five-point categorical scale. Categories are cap–ridge–saddle–rut–cup–flat, where “flat” denotes the absence of shape. We find that observers readily perform such a task, with full resolution of a shape index scale (cap–ridge–saddle–rut–cup), and with excellent self-consistency over days. There exist remarkable inter-observer differences. Over a group of 10 naive observers we find that the dispersion of judgments peaks at the saddle category. There may be a relation of this finding to the history of the topic—Alberti's (1827) omission of the saddle category in his purportedly exhaustive catalog of local surface shapes. PMID:25469225

A laser-induced heat flux technique for convective heat transfer measurements in high speed flows

NASA Technical Reports Server (NTRS)

Porro, A. R.; Keith, T. G., Jr.; Hingst, W. R.

1991-01-01

A technique is developed to measure the local convective heat transfer coefficient on a model surface in a supersonic flow field. The technique uses a laser to apply a discrete local heat flux at the model test surface, and an infrared camera system determines the local temperature distribution due to the heating. From this temperature distribution and an analysis of the heating process, a local convective heat transfer coefficient is determined. The technique was used to measure the local surface convective heat transfer coefficient distribution on a flat plate at nominal Mach numbers of 2.5, 3.0, 3.5, and 4.0. The flat plate boundary layer initially was laminar and became transitional in the measurement region. The experimentally determined convective heat transfer coefficients were generally higher than the theoretical predictions for flat plate laminar boundary layers. However, the results indicate that this nonintrusive optical measurement technique has the potential to measure surface convective heat transfer coefficients in high speed flow fields.

A laser-induced heat flux technique for convective heat transfer measurements in high speed flows

NASA Technical Reports Server (NTRS)

Porro, A. R.; Keith, T. G., Jr.; Hingst, W. R.

1991-01-01

A technique is developed to measure the local convective heat transfer coefficient on a model surface in a supersonic flow field. The technique uses a laser to apply a discrete local heat flux at the model test surface, and an infrared camera system determines the local temperature distribution due to the heating. From this temperature distribution and an analysis of the heating process, a local convective heat transfer coefficient is determined. The technique was used to measure the local surface convective heat transfer coefficient distribution on a flat plate at nominal Mach numbers of 2.5, 3.0, 3.5, and 4.0. The flat plate boundary layer initially was laminar and became transitional in the measurement region. The experimentally determined convective heat transfer coefficients were generally higher than the theoretical predictions for flat plate laminar boundary layers. However, the results indicate that this nonintrusive optical measurement technique has the potential to measure surface convective heat transfer coefficients in high-speed flowfields.

The limits of local correlation theory: electronic delocalization and chemically smooth potential energy surfaces.

PubMed

Subotnik, Joseph E; Sodt, Alex; Head-Gordon, Martin

2008-01-21

Local coupled-cluster theory provides an algorithm for measuring electronic correlation quickly, using only the spatial locality of localized electronic orbitals. Previously, we showed [J. Subotnik et al., J. Chem. Phys. 125, 074116 (2006)] that one may construct a local coupled-cluster singles-doubles theory which (i) yields smooth potential energy surfaces and (ii) achieves near linear scaling. That theory selected which orbitals to correlate based only on the distances between the centers of different, localized orbitals, and the approximate potential energy surfaces were characterized as smooth using only visual identification. This paper now extends our previous algorithm in three important ways. First, locality is now based on both the distances between the centers of orbitals as well as the spatial extent of the orbitals. We find that, by accounting for the spatial extent of a delocalized orbital, one can account for electronic correlation in systems with some electronic delocalization using fast correlation methods designed around orbital locality. Second, we now enforce locality on not just the amplitudes (which measure the exact electron-electron correlation), but also on the two-electron integrals themselves (which measure the bare electron-electron interaction). Our conclusion is that we can bump integrals as well as amplitudes, thereby gaining a tremendous increase in speed and paradoxically increasing the accuracy of our LCCSD approach. Third and finally, we now make a rigorous definition of chemical smoothness as requiring that potential energy surfaces not support artificial maxima, minima, or inflection points. By looking at first and second derivatives from finite difference techniques, we demonstrate complete chemical smoothness of our potential energy surfaces (bumping both amplitudes and integrals). These results are significant both from a theoretical and from a computationally practical point of view.

Band gaps and localization of surface water waves over large-scale sand waves with random fluctuations

NASA Astrophysics Data System (ADS)

Zhang, Yu; Li, Yan; Shao, Hao; Zhong, Yaozhao; Zhang, Sai; Zhao, Zongxi

2012-06-01

Band structure and wave localization are investigated for sea surface water waves over large-scale sand wave topography. Sand wave height, sand wave width, water depth, and water width between adjacent sand waves have significant impact on band gaps. Random fluctuations of sand wave height, sand wave width, and water depth induce water wave localization. However, random water width produces a perfect transmission tunnel of water waves at a certain frequency so that localization does not occur no matter how large a disorder level is applied. Together with theoretical results, the field experimental observations in the Taiwan Bank suggest band gap and wave localization as the physical mechanism of sea surface water wave propagating over natural large-scale sand waves.

Gold Nanoparticles with Externally Controlled, Reversible Shifts of Local Surface Plasmon Resonance Bands

PubMed Central

Yavuz, Mustafa S.; Jensen, Gary C.; Penaloza, David P.; Seery, Thomas A. P.; Pendergraph, Samuel A.; Rusling, James F.; Sotzing, Gregory A.

2010-01-01

We have achieved reversible tunability of local surface plasmon resonance in conjugated polymer functionalized gold nanoparticles. This property was facilitated by the preparation of 3,4-ethylenedioxythiophene (EDOT) containing polynorbornene brushes on gold nanoparticles via surface-initiated ring-opening metathesis polymerization. Reversible tuning of the surface plasmon band was achieved by electrochemically switching the EDOT polymer between its reduced and oxidized states. PMID:19839619

Development of Erosive Burning Models for CFD Predictions of Solid Rocket Motor Internal Environments

NASA Technical Reports Server (NTRS)

Wang, Qun-Zhen

2003-01-01

Four erosive burning models, equations (11) to (14). are developed in this work by using a power law relationship to correlate (1) the erosive burning ratio and the local velocity gradient at propellant surfaces; (2) the erosive burning ratio and the velocity gradient divided by centerline velocity; (3) the erosive burning difference and the local velocity gradient at propellant surfaces; and (4) the erosive burning difference and the velocity gradient divided by centerline velocity. These models depend on the local velocity gradient at the propellant surface (or the velocity gradient divided by centerline velocity) only and, unlike other empirical models, are independent of the motor size. It was argued that, since the erosive burning is a local phenomenon occurring near the surface of the solid propellant, the erosive burning ratio should be independent of the bore diameter if it is correlated with some local flow parameters such as the velocity gradient at the propellant surface. This seems to be true considering the good results obtained by applying these models, which are developed from the small size 5 inch CP tandem motor testing, to CFD simulations of much bigger motors.

Spatial dispersion in atom-surface quantum friction

DOE PAGES

Reiche, D.; Dalvit, D. A. R.; Busch, K.; ...

2017-04-15

We investigate the influence of spatial dispersion on atom-surface quantum friction. We show that for atom-surface separations shorter than the carrier's mean free path within the material, the frictional force can be several orders of magnitude larger than that predicted by local optics. In addition, when taking into account spatial dispersion effects, we show that the commonly used local thermal equilibrium approximation underestimates by approximately 95% the drag force, obtained by employing the recently reported nonequilibrium fluctuation-dissipation relation for quantum friction. Unlike the treatment based on local optics, spatial dispersion in conjunction with corrections to local thermal equilibrium change notmore » only the magnitude but also the distance scaling of quantum friction.« less

Operator Localization of Virtual Objects

NASA Technical Reports Server (NTRS)

Ellis, Stephen R.; Menges, Brian M.; Null, Cynthia H. (Technical Monitor)

1998-01-01

Errors in the localization of nearby virtual objects presented via see-through, helmet mounted displays are examined as a function of viewing conditions and scene content. Monocular, biocular or stereoscopic presentation of the virtual objects, accommodation (required focus), subjects'age, and the position of physical surfaces are examined. Nearby physical surfaces are found to introduce localization errors that differ depending upon the other experimental factors. The apparent physical size and transparency of the virtual objects and physical surfaces respectively are also influenced by their relative position when superimposed. Design implications are discussed.

3D skin surface reconstruction from a single image by merging global curvature and local texture using the guided filtering for 3D haptic palpation.

PubMed

Lee, K; Kim, M; Kim, K

2018-05-11

Skin surface evaluation has been studied using various imaging techniques. However, all these studies had limited impact because they were performed using visual exam only. To improve on this scenario with haptic feedback, we propose 3D reconstruction of the skin surface using a single image. Unlike extant 3D skin surface reconstruction algorithms, we utilize the local texture and global curvature regions, combining the results for reconstruction. The first entails the reconstruction of global curvature, achieved by bilateral filtering that removes noise on the surface while maintaining the edge (ie, furrow) to obtain the overall curvature. The second entails the reconstruction of local texture, representing the fine wrinkles of the skin, using an advanced form of bilateral filtering. The final image is then composed by merging the two reconstructed images. We tested the curvature reconstruction part by comparing the resulting curvatures with measured values from real phantom objects while local texture reconstruction was verified by measuring skin surface roughness. Then, we showed the reconstructed result of our proposed algorithm via the reconstruction of various real skin surfaces. The experimental results demonstrate that our approach is a promising technology to reconstruct an accurate skin surface with a single skin image. We proposed 3D skin surface reconstruction using only a single camera. We highlighted the utility of global curvature, which has not been considered important in the past. Thus, we proposed a new method for 3D reconstruction that can be used for 3D haptic palpation, dividing the concepts of local and global regions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The concept of geodesic curvature applied to optical surfaces.

PubMed

Barbero, Sergio

2015-07-01

To propose geodesic curvature as a metric to characterise how an optical surface locally differs from axial symmetry. To derive equations to evaluate geodesic curvatures of arbitrary surfaces expressed in polar coordinates. The concept of geodesic curvature is explained in detail as compared to other curvature-based metrics. Starting with the formula representing a surface as function of polar coordinates, an equation for the geodesic curvature is obtained depending only on first and second radial and first order angular derivatives of the surface function. The potential of the geodesic curvature is illustrated using different surface tests. Geodesic curvature reveals local axial asymmetries more sharply than other types of curvatures such as normal curvatures. Geodesic curvature maps could be used to characterise local axial asymmetries for relevant optometry applications such as corneal topography anomalies (keratoconus) or ophthalmic lens metrology. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Investigation of the effect of sealed surfaces on local climate in urban areas

NASA Astrophysics Data System (ADS)

Weihs, Philipp; Hasel, Stefan; Mursch-Radlgruber, Erich; Gützer, Christian; Krispel, Stefan; Peyerl, Martin; Trimmel, Heidi

2015-04-01

Local climate is driven by the interaction between energy balance and energy transported by advected air. Short-wave and long-wave radiation are major components in this interaction. Some few studies (e.g. Santamouris et al.) showed that adjusting the grade of reflection of surfaces is an efficient way to influence temperature. The present study investigates the influence of high albedo concrete surfaces on local climate. The first step of the study consisted of experimental investigations: routine measurements of the short and longwave radiation balance, of the ground and of the air temperature and humidity at different heights above 6 different types of sealed surfaces were performed. During this measurement campaign the above mentioned components were measured over a duration of 4 months above two conventional asphalt surfaces, one conventional concrete and three newly developed concrete surfaces with increased reflectances. Measured albedo values amounted to 0.12±0.02 for the asphalt surfaces and to maximum values of 0.56 for high albedo concrete. The maximum difference in surface temperature between the asphalt surfaces and the high albedo concrete surfaces amounted to 15°C. In addition the emission constants of the different sealed surfaces were also determined and were compared to values from literature.. In a second step the urban energy balance model Envi_Met was used to simulate the surface temperature of the six surfaces. The simulated surface temperatures were compared to the measured surface temperatures and statements as to uncertainties of the model simulations were made In a third step, Envi_Met was used to simulate the local climate of an urban district in Vienna. The surface and air temperature and the SW, LW fluxes were calculated for different types of sealed surfaces. By performing calculations of thermal stress indices (UTCI, PMV), statements as to the influence of the type of sealed surface on thermal stress on humans was made.

Local Turbulence Suppression and Shear Flow Dynamics During qmin-Triggered Internal Transport Barriers on DIII-D

NASA Astrophysics Data System (ADS)

Shafer, M. W.; McKee, G. R.; Schlossberg, D. J.; Austin, M. E.; Burrell, K. H.

2008-11-01

Long-wavelength turbulence (kρi< 1) is locally suppressed simultaneously with a rapid but transient increase in local poloidal flow shear at the appearance of low-order rational qmin surfaces in negative central shear discharges. At these events, reductions in energy transport are observed and Internal Transport Barriers (ITBs) may form. Application of off-axis ECH slows the q-profile evolution and increases ρqmin, both of which enhance turbulence measurements using a new high-sensitivity large-area (8x,8) 2D BES array. The measured transient turbulence suppression is localized to the low-order rational surface (qmin= 2, 5/2, 3, etc.). Measured poloidal flow shear transiently exceeds the turbulence decorrelation rate, which is consistent with shear suppression. The localized suppression zone propagates radially outward, nearly coincident with the low-order surface.

Immunogenicity and thermal stability of a combined vaccine against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases.

PubMed

Saydam, Manolya; Burkin, Karena; Care, Rory; Rigsby, Peter; Bolgiano, Barbara; Mawas, Fatme

2010-08-31

The immunogenicity, structure and stability of a combined conjugate vaccine against Haemophilus influenzae type b and meningococcal serogroup C (Hib/MenC) were investigated. A rat model for immunogenicity showed that antibody responses to Hib and MenC in the combined vaccine were similar to or higher than those of individual conjugates given alone, or concomitantly at separate sites. At elevated temperatures, the combination vaccine was slightly more stable than a monovalent Hib-TT vaccine, with respect to molecular size, which could be attributed to differences in the formulations. Following 5 weeks incubation at 56 degrees C, there was some dissociation of high molecular weight conjugate without significant loss of saccharide integrity; however, this did not significantly affect the vaccine immunogenicity, demonstrating the stability of this lyophilized vaccine. (c) 2010 Elsevier Ltd. All rights reserved.

Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence

PubMed Central

Mahdavi, Jafar; Royer, Pierre-Joseph; Sjölinder, Hong S.; Azimi, Sheyda; Self, Tim; Stoof, Jeroen; Wheldon, Lee M.; Brännström, Kristoffer; Wilson, Raymond; Moreton, Joanna; Moir, James W. B.; Sihlbom, Carina; Borén, Thomas; Jonsson, Ann-Beth; Soultanas, Panos; Ala'Aldeen, Dlawer A. A.

2013-01-01

Interactions between commensal pathogens and hosts are critical for disease development but the underlying mechanisms for switching between the commensal and virulent states are unknown. We show that the human pathogen Neisseria meningitidis, the leading cause of pyogenic meningitis, can modulate gene expression via uptake of host pro-inflammatory cytokines leading to increased virulence. This uptake is mediated by type IV pili (Tfp) and reliant on the PilT ATPase activity. Two Tfp subunits, PilE and PilQ, are identified as the ligands for TNF-α and IL-8 in a glycan-dependent manner, and their deletion results in decreased virulence and increased survival in a mouse model. We propose a novel mechanism by which pathogens use the twitching motility mode of the Tfp machinery for sensing and importing host elicitors, aligning with the inflamed environment and switching to the virulent state. PMID:24107297

Rapid differentiation of rocky mountain spotted fever from chickenpox, measles, and enterovirus infections and bacterial meningitis by frequency-pulsed electron capture gas-liquid chromatographic analysis of sera.

PubMed Central

Brooks, J B; McDade, J E; Alley, C C

1981-01-01

Normal sera and sera from patients with Rocky Mountain spotted fever, chickenpox, enterovirus infections, measles, and Neisseria meningitidis infections were extracted with organic solvents under acidic and basic conditions and then derivatized with trichloroethanol or heptafluorobutyric anhydride-ethanol to form electron-capturing derivatives of organic acids, alcohols, and amines. The derivatives were analyzed by frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC). There were unique differences in the FPEC-GLC profiles of sera obtained from patients with these respective diseases. With Rocky Mountain spotted fever patients, typical profiles were detected as early as 1 day after onset of disease and before antibody could be detected in the serum. Rapid diagnosis of Rocky Mountain spotted fever by FPEC-GLC could permit early and effective therapy, thus preventing many deaths from this disease. PMID:7276147

A mathematical model for evaluating the impact of vaccination schedules: application to Neisseria meningitidis.

PubMed

Tuckwell, H C; Hanslik, T; Valleron, A J; Flahault, A

2003-06-01

A mathematical model is described which determines the impact of a schedule of vaccination on the time course of a certain class of diseases. The data are the demographic variables and parameters and age-dependent non-fatal and fatal case rates. Given the age- and time-dependent rates of vaccination including coverage and corresponding efficacies, various schedules may be distinguished by either the absolute numbers of cases and deaths avoided or the numbers of cases and deaths avoided per dose of vaccine. The model was applied to meningo-coccal serogroup C disease in France. The outcomes of six different vaccination schedules were examined. In absolute terms, a schedule in which all individuals aged between 2 and 20 years were vaccinated performed best, but this schedule and that in which only 1-year olds were vaccinated performed equally and best in terms of cases prevented, but not lives saved, per dose.

Detection of bacterial growth by gas absorption.

PubMed

Waters, J R

1992-05-01

When 24 different aerobic organisms were grown in a shaken culture, all were found to first absorb gas from the headspace. In a rudimentary medium, such as tryptic soy broth, 16 of the 24 organisms did not produce gas following the initial gas absorption. We have developed a simple, noninvasive method for detecting both gas absorption and production in multiple culture vials. The time to positivity was compared with that obtained by the BACTEC 460 blood culture system. For nearly all of these organisms, there was no difference. For some of those organisms that did not produce gas, e.g. Staphylococcus epidermidis, Moraxella osloensis, and Neisseria meningitidis, detection by gas absorption was a few hours faster. Gas absorption appears to be a promising technique for a new automated blood culture system because of its simplicity and because medium without special additives can be used to detect organisms that do not produce gas.

Determinants of case fatality rates of meningococcal disease during outbreaks in Makkah, Saudi Arabia, 1987-97.

PubMed Central

El Bushra, H. E.; Hassan, N. M.; Al-Hamdan, N. A.; Al-Jeffri, M. H.; Turkistani, A. M.; Al-Jumaily, A.; Ali, M. A.; Rahama, A. M.

2000-01-01

We studied case-fatality rates (CFRs) among cases of meningococcal disease (MCD) admitted to Makkah (Saudi Arabia) hospitals during the period 1988-97. Of 483 cases, 431 (89.2%) were due to strains of serogroup A, 31 (6.4%) to serogroup W135, 16 (3.3%) to serogroup C, and 5 (10%) to serogroup B. Eighty-one patients died (case fatality rate (CFR)) 16.8%, 95% CI 13.5%, 20.4%). The CFR in infections due to serogroup A strains was 14.8%, and for other serogroups it was 32.7% (95% CI 20.3%, 47.1%). The CFR of MCD due to N. meningitidis serogroup A increased steadily with age (P<0.05). Seeking first medical help at a foreign Hajj medical mission and being treated in a non-specialized hospital were associated with a higher case fatality rate. PMID:11218206

[Conjugated vaccines].

PubMed

Fritzell, Bernard

2005-01-01

Encapsulated bacterial pathogens (e.g. Haemophilus influenzae type b [Hib], Neisseria meningitidis, or Streptococcus pneumoniae) target infants and young children who have lost any protective anti-capsular antibodies supplied maternally and whose immune systems are ineffective against T-independent antigens such as the polysaccharides of the capsule. The polysaccharide-protein conjugate vaccines overcome this limitation by converting the polysaccharide to a T-dependent antigen, which allows a vaccinated infant to mount a protective immune response. Where conjugated vaccines have been introduced into paediatric vaccination schedules, the incidence of invasive diseases caused by Hib, the group C meningococcus, or the pneumococcus has plummeted by at least 80%, a major public health success. Furthermore, surveillance has demonstrated that the conjugate vaccines provide 'herd protection' through their beneficial impact on nasopharyngeal colonisation among vaccinated children. Promising future approaches include enhancement of the number of capsular serogroups targeted by the meningococcal or pneumococcal conjugate vaccines.

[Meningococcal vaccines. Global epidemiological situation and strategies for prevention by vaccination].

PubMed

Rivero Calle, Irene; Rodriguez-Tenreiro Sánchez, Carmen; Martinón-Torres, Federico

2015-04-01

N. meningitidis is a major cause of meningitis and septicemia and a major public health problem in many countries. The disease, that can be fulminant, has a high mortality and may cause serious sequelae, even in cases of apparently optimal medical treatment. Chemoprophylaxis may prevent secondary cases among those in close contact with the ill, but, since secondary cases represent only 1%-2% of all meningococcal disease, chemoprophylaxis has a small impact when fighting most of endemic and epidemic forms. Given that al least 5% -15% of children and young adults are carriers, the fight against meningococcal disease based on chemotherapeutic elimination of nasopharyngeal colonization is virtually impossible. Therefore, immunization is the only rational way to combat this disease. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

[Meningococcus profilaxis (author's transl)].

PubMed

Pérez Trallero, E; Pérez-Yarza, E; Ruíz Benito, C; Muñóz Baroja, I

1979-11-25

In a General Hospital in San Sebastian, 96 cases of Neisseria meningitidis infections were detected in a two years period. By the use of the disk diffusion method, we found that all causative meningococcal strains but 4 were resistant to sulfonamide (with a 300 microgram sulfadiazine disk, all isolates with a zone diameter of less than 20 mm were considered to be resistant of sulfadiazine, whereas those with zone diameters of greater than 30 mm were considered susceptible). No rifampin nor minocycline-resistant meningococci were isolated. All strains had a disk zone diameter (30 micrograms rifampin and 30 micrograms tetracycline) of greater than 20 mm. The serogroups of meningococcal strains were as follows: group A, 1; group B, 67; group C, 5 and 23 were no typed. Children less than four years of age were most frequently attacked (67,7%). The attack rate was only slightly higher in males than in females (52 and 44).

Risk factors for community-acquired bacterial meningitis.

PubMed

Lundbo, Lene Fogt; Benfield, Thomas

2017-06-01

Bacterial meningitis is a significant burden of disease and mortality in all age groups worldwide despite the development of effective conjugated vaccines. The pathogenesis of bacterial meningitis is based on complex and incompletely understood host-pathogen interactions. Some of these are pathogen-specific, while some are shared between different bacteria. We searched the database PubMed to identify host risk factors for bacterial meningitis caused by the pathogens Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b, because they are three most common causative bacteria beyond the neonatal period. We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults. As conjugated vaccines are available for these infections, it is of utmost importance to identify high risk patients to be able to prevent invasive disease.

An Investigation of Land-Atmosphere Coupling from Local to Regional Scales

NASA Astrophysics Data System (ADS)

Brunsell, N. A.; Van Vleck, E.; Rahn, D. A.

2017-12-01

The exchanges of mass and energy between the surface and atmosphere have been shown to depend upon both local and regional climatic influences. However, the degree of control exerted by the land surface on the coupling metrics is not well understood. In particular, we lack an understanding of the relationship between the local microclimate of a site and the regional forces responsible for land-atmosphere coupling. To address this, we investigate a series of metrics calculated from eddy covariance data and ceilometer data, land surface modeling and remotely sensed observations in the central United States to diagnose these interactions and predict the change from one coupling regime (e.g. wet/dry coupling) to another state. The stability of the coupling is quantified using a Lyapunov exponent based methodology. Through the use of a wavelet information theoretic approach, we isolate the roles local energy partitioning, as well as the temperature and moisture gradients on controlling and changing the coupling regime. Taking a multi-scale observational approach, we first examine the relationship at the tower scale. Using land surface models, we quantify to what extent current models are capable of properly diagnosing the dynamics of the coupling regime. In particular, we focus on the role of the surface moisture and vegetation to initiate and maintain precipitation feedbacks. We extend this analysis to the regional scale by utilizing reanalysis and remotely sensed observations. Thus, we are able to quantify the changes in observed coupling patterns with linkages to local interactions to address the question of the local control that the surface exerts over the maintenance of land-atmosphere coupling.

Evolutionary-inspired probabilistic search for enhancing sampling of local minima in the protein energy surface

PubMed Central

2012-01-01

Background Despite computational challenges, elucidating conformations that a protein system assumes under physiologic conditions for the purpose of biological activity is a central problem in computational structural biology. While these conformations are associated with low energies in the energy surface that underlies the protein conformational space, few existing conformational search algorithms focus on explicitly sampling low-energy local minima in the protein energy surface. Methods This work proposes a novel probabilistic search framework, PLOW, that explicitly samples low-energy local minima in the protein energy surface. The framework combines algorithmic ingredients from evolutionary computation and computational structural biology to effectively explore the subspace of local minima. A greedy local search maps a conformation sampled in conformational space to a nearby local minimum. A perturbation move jumps out of a local minimum to obtain a new starting conformation for the greedy local search. The process repeats in an iterative fashion, resulting in a trajectory-based exploration of the subspace of local minima. Results and conclusions The analysis of PLOW's performance shows that, by navigating only the subspace of local minima, PLOW is able to sample conformations near a protein's native structure, either more effectively or as well as state-of-the-art methods that focus on reproducing the native structure for a protein system. Analysis of the actual subspace of local minima shows that PLOW samples this subspace more effectively that a naive sampling approach. Additional theoretical analysis reveals that the perturbation function employed by PLOW is key to its ability to sample a diverse set of low-energy conformations. This analysis also suggests directions for further research and novel applications for the proposed framework. PMID:22759582

The Thioredoxin Domain of Neisseria Gonorrhoeae PilB can use Electrons from DsbD to Reduce Downstream Methionine Sulfoxide Reductases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brot,N.; Collet, J.; Johnson, L.

2006-01-01

The PilB protein from Neisseria gonorrhoeae is located in the periplasm and made up of three domains. The N-terminal, thioredoxin-like domain (NT domain) is fused to tandem methionine sulfoxide reductase A and B domains (MsrA/B). We show that the {alpha} domain of Escherichia coli DsbD is able to reduce the oxidized NT domain, which suggests that DsbD in Neisseria can transfer electrons from the cytoplasmic thioredoxin to the periplasm for the reduction of the MsrA/B domains. An analysis of the available complete genomes provides further evidence for this proposition in other bacteria where DsbD/CcdA, Trx, MsrA, and MsrB gene homologsmore » are all located in a gene cluster with a common transcriptional direction. An examination of wild-type PilB and a panel of Cys to Ser mutants of the full-length protein and the individually expressed domains have also shown that the NT domain more efficiently reduces the MsrA/B domains when in the polyprotein context. Within this framework there does not appear to be a preference for the NT domain to reduce the proximal MsrA domain over MsrB domain. Finally, we report the 1.6 {angstrom} crystal structure of the NT domain. This structure confirms the presence of a surface loop that makes it different from other membrane-tethered, Trx-like molecules including TlpA, CcmG and ResA. Subtle differences are observed in this loop when compared to the N. meningitidis NT domain structure. The data taken together supports the formation of specific NT domain interactions with the MsrA/B domains and its in vivo recycling partner, DsbD.« less

Synthesis of orthogonally protected bacterial, rare-sugar and D-glycosamine building blocks.

PubMed

Emmadi, Madhu; Kulkarni, Suvarn S

2013-10-01

Bacterial glycoconjugates comprise atypical deoxy amino sugars that are not present on the human cell surface, making them good targets for drug discovery and carbohydrate-based vaccine development. Unfortunately, they cannot be isolated with sufficient purity in acceptable amounts, and therefore chemical synthesis is a crucial step toward the development of these products. Here we describe a detailed protocol for the synthesis of orthogonally protected bacterial deoxy amino hexopyranoside (2,4-diacetamido-2,4,6-trideoxyhexose (DATDH), D-bacillosamine, D-fucosamine, and 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose (AAT)), D-glucosamine and D-galactosamine building blocks starting from β-D-thiophenylmannoside. Readily available β-D-thiophenylmannoside was first converted into the corresponding 2,4-diols via deoxygenation or silylation at C6, followed by O3 acylation. The 2,4-diols were converted into 2,4-bis-trifluoromethanesulfonates, which underwent highly regioselective, one-pot, double-serial and double-parallel displacements by azide, phthalimide, acetate and nitrite ions as nucleophiles. Thus, D-rhamnosyl- and D-mannosyl 2,4-diols can be efficiently transformed into various rare sugars and D-galactosamine, respectively, as orthogonally protected thioglycoside building blocks on a gram scale in 1-2 d, in 54-85% overall yields, after a single chromatographic purification. This would otherwise take 1-2 weeks. D-Glucosamine building blocks can be prepared from β-D-thiophenylmannoside in four steps via C2 displacement of triflates by azide in 2 d and in 66-70% overall yields. These procedures have been applied to the synthesis of L-serine-linked trisaccharide of Neisseria meningitidis and a rare disaccharide fragment of the zwitterionic polysaccharide (ZPS) A1 (ZPS A1) of Bacteroides fragilis.

Anisotropic Dispersion and Partial Localization of Acoustic Surface Plasmons on an Atomically Stepped Surface: Au(788)

NASA Astrophysics Data System (ADS)

Smerieri, M.; Vattuone, L.; Savio, L.; Langer, T.; Tegenkamp, C.; Pfnür, H.; Silkin, V. M.; Rocca, M.

2014-10-01

Understanding acoustic surface plasmons (ASPs) in the presence of nanosized gratings is necessary for the development of future devices that couple light with ASPs. We show here by experiment and theory that two ASPs exist on Au(788), a vicinal surface with an ordered array of monoatomic steps. The ASPs propagate across the steps as long as their wavelength exceeds the terrace width, thereafter becoming localized. Our investigation identifies, for the first time, ASPs coupled with intersubband transitions involving multiple surface-state subbands.

Immunocytochemical localization of muscarinic, adrenergic and AT1 receptors.

PubMed

Schulze, W; Fu, M L

1996-01-01

By indirect immunofluorescence and post-embedding EM gold technique, the localization of alpha 1-adrenergic, M2-muscarinic and angiotensin II receptor-I (AT1) were determinated. With antipeptide antibodies directed against the second extracellular loops of all three receptors, these receptors were found to be localized at the sarcolemma of adult rat cardiomyocytes and at the surface membranes of cultivated neonatal heart cells. Additionally, M2 receptors were localized along T-tubule membranes of both rat and human adult cardiomyocytes. alpha 1-Adrenergic receptors were found intracellular near the surface of atrial granules (ANF-granules). By using M2 and alpha 1-adrenergic receptor antibodies the strongest fluorescence was found in the right atrium of the rat. Besides the localization in cardiomyocytes, AT1 receptors were also localized in outer plasma membranes and the endoplasmic reticulum of fibroblasts, and the surface of smooth muscle cells of the major arteries and veins. Likewise, the muscarinic M2 receptors were found along the outer membranes of endothelial cells from capillaries and endocardium.

Spatially Probed Plasmonic Photothermic Nanoheater Enhanced Hybrid Polymeric-Metallic PVDF-Ag Nanogenerator.

PubMed

Liow, Chi Hao; Lu, Xin; Tan, Chuan Fu; Chan, Kwok Hoe; Zeng, Kaiyang; Li, Shuzhou; Ho, Ghim Wei

2018-02-01

Surface plasmon-based photonics offers exciting opportunities to enable fine control of the site, span, and extent of mechanical harvesting. However, the interaction between plasmonic photothermic and piezoresponse still remains underexplored. Here, spatially localized and controllable piezoresponse of a hybrid self-polarized polymeric-metallic system that correlates to plasmonic light-to-heat modulation of the local strain is demonstrated. The piezoresponse is associated to the localized plasmons that serve as efficient nanoheaters leading to self-regulated strain via thermal expansion of the electroactive polymer. Moreover, the finite-difference time-domain simulation and linear thermal model also deduce the local strain to the surface plasmon heat absorption. The distinct plasmonic photothermic-piezoelectric phenomenon mediates not only localized external stimulus light response but also enhances dynamic piezoelectric energy harvesting. The present work highlights a promising surface plasmon coordinated piezoelectric response which underpins energy localization and transfer for diversified design of unique photothermic-piezotronic technology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural Features of the Pseudomonas fluorescens Biofilm Adhesin LapA Required for LapG-Dependent Cleavage, Biofilm Formation, and Cell Surface Localization

PubMed Central

Boyd, Chelsea D.; Smith, T. Jarrod; El-Kirat-Chatel, Sofiane; Newell, Peter D.; Dufrêne, Yves F.

2014-01-01

The localization of the LapA protein to the cell surface is a key step required by Pseudomonas fluorescens Pf0-1 to irreversibly attach to a surface and form a biofilm. LapA is a member of a diverse family of predicted bacterial adhesins, and although lacking a high degree of sequence similarity, family members do share common predicted domains. Here, using mutational analysis, we determine the significance of each domain feature of LapA in relation to its export and localization to the cell surface and function in biofilm formation. Our previous work showed that the N terminus of LapA is required for cleavage by the periplasmic cysteine protease LapG and release of the adhesin from the cell surface under conditions unfavorable for biofilm formation. We define an additional critical region of the N terminus of LapA required for LapG proteolysis. Furthermore, our results suggest that the domains within the C terminus of LapA are not absolutely required for biofilm formation, export, or localization to the cell surface, with the exception of the type I secretion signal, which is required for LapA export and cell surface localization. In contrast, deletion of the central repetitive region of LapA, consisting of 37 repeats of 100 amino acids, results in an inability to form a biofilm. We also used single-molecule atomic force microscopy to further characterize the role of these domains in biofilm formation on hydrophobic and hydrophilic surfaces. These studies represent the first detailed analysis of the domains of the LapA family of biofilm adhesin proteins. PMID:24837291

Local dynamics of glass-forming polystyrene thin films from atomistic simulation

NASA Astrophysics Data System (ADS)

Zhou, Yuxing; Milner, Scott

Despite a wide technological application ranging from protective coatings to organic solar cells, there still no consensus on the mechanism for the glass transition in polymer thin films a manifestation of the infamous glass problem under confinement. Many experimental and computational studies have observed a large deviation of nanoscale dynamical properties in thin films from the corresponding properties in bulk. In this work, we perform extensive united-atom simulations on atactic polystyrene free-standing thin films near the glass transition temperature and focus on the effect of free surface on the local dynamics. We study the segmental dynamics as a function of distance from the surface for different temperatures, from which relaxation time and thereby local Tg is obtained for each layer. We find the dynamics near free surface is not only enhanced but becomes less strongly temperature dependent as Tg is approached compared to the bulk. We find an increasing length scale associated with mobility propagation from the free surface as temperature decreases, but no correlation between local structure and enhanced relaxation rates near the surface, consistent with studies on bead-spring chains.

Surface infrastructure : cost, financing and schedules for large-dollar transportation projects

DOT National Transportation Integrated Search

1998-02-01

In fiscal year 1998, the federal government will distribute nearly $26 billion to states and localities for the construction and repair of the nation's surface transportation systems. To meet the nations' transportation needs, states and localities a...

A preliminary assessment of land-surface subsidence in the El Paso area, Texas

USGS Publications Warehouse

Land, L.F.; Armstrong, C.A.

1985-01-01

In addition to regional subsidence, local subsidence is indicated by observable surface fractures but has not been verified by precise leveling. These local areas coincide with areas that historically were swamps along the Rio Grande.

Non-radiative processes dominate land surface signals in the climate system

NASA Astrophysics Data System (ADS)

Bright, R. M.; Davin, E.; O'Halloran, T. L.; Pongratz, J.; Zhao, K.; Cescatti, A.

2016-12-01

Perturbations to the surface energy budget linked to land cover/land management changes (LCMC) are rarely included in land-climate assessments although they have long been recognized as important drivers of local climate change. At local scales, climate forcings from LCMC depend strongly on changes to surface energy redistribution by various non-radiative mechanisms, dampening or even outweighing the local radiative effect of an albedo change. The extent to which these mechanisms are locally relevant for different types of LCMC across the world remains largely unquantified. Here, we combine extensive records of remote sensing and in-situ observations to quantify local forcings for nine common real-world LCMC perturbations, identifying their underlying physical mechanisms and analyzing their spatial patterns at the global scale. We find that throughout the densely populated regions, non-radiative forcings dominate the local surface temperature response in 8 of 9 LCMC scenarios. Further, the observed local response to re-/afforestation is an annual cooling in all regions south of the upper conterminous United States, Western Europe, and Indo-China. Given that the global response to re-/afforestation in these regions is likely a cooling, projects here can be seen as attractive mitigation measures. Our results - gridded to a 1° x 1° resolution - can be directly used to evaluate climate models or compute indicators providing a more comprehensive picture of the trade-offs between local and global climate forcings linked to land sector projects and policies.

Impact of nitinol stent surface processing on in-vivo nickel release and biological response.

PubMed

Nagaraja, Srinidhi; Sullivan, Stacey J L; Stafford, Philip R; Lucas, Anne D; Malkin, Elon

2018-05-01

Although nitinol is widely used in percutaneous cardiovascular interventions, a causal relationship between nickel released from implanted cardiovascular devices and adverse systemic or local biological responses has not been established. The objective of this study was to investigate the relationship between nitinol surface processing, in-vivo nickel release, and biocompatibility. Nitinol stents manufactured using select surface treatments were implanted into the iliac arteries of minipigs for 6 months. Clinical chemistry profile, complete blood count, serum and urine nickel analyses were performed periodically during the implantation period. After explant, stented arteries were either digested and analyzed for local nickel concentration or fixed and sectioned for histopathological analysis of stenosis and inflammation within the artery. The results indicated that markers for liver and kidney function were not different than baseline values throughout 180 days of implantation regardless of surface finish. In addition, white blood cell, red blood cell, and platelet counts were similar to baseline values for all surface finishes. Systemic nickel concentrations in serum and urine were not significantly different between processing groups and comparable to baseline values during 180 days of implantation. However, stents with non-optimized surface finishing had significantly greater nickel levels in the surrounding artery compared to polished stents. These stents had increased stenosis with potential for local inflammation compared to polished stents. These findings demonstrate that proper polishing of nitinol surfaces can reduce in-vivo nickel release locally, which may aid in minimizing adverse inflammatory reactions and restenosis. Nitinol is a commonly used material in cardiovascular medical devices. However, relationships between nitinol surface finishing, in-vivo metal ion release, and adverse biological responses have yet to be established. We addressed this knowledge gap by implanting single and overlapped nitinol stents with different surface finishes to assess systemic impact on minipigs (i.e. serum and urine nickel levels, liver and kidney function, immune and blood count) over the 6 month implantation period. In addition, nickel levels and histopathology in stented arteries were analyzed on explant to determine relationships between surface processing and local adverse tissue reactions. The findings presented here highlight the importance of surface processing on in-vivo nickel release and subsequent impact on local biological response for nitinol implants. Published by Elsevier Ltd.

Surface Temperature Prediction of a Bridge for Tactical Decision Aide Modelling

DTIC Science & Technology

1988-01-01

Roadway And Piling Surface Temperature Predictions (No Radiosity Incident on Lower Surface) Compared to Temperature Estimates...Heat gained from water = Heat lost by long wave radiosity radiation. Algebraically, with the conduction term expressed in the same manner as for...5 10 15 20 LOCAL TIME (hrs.) Figure 8. Effect of No Radiosity Incident on Lower Surface. 37 U 8a M OT U% 60-- 0- o.. 20- 0- 1 T I I 5 10 15 20 LOCAL

Tuning Nanocrystal Surface Depletion by Controlling Dopant Distribution as a Route Toward Enhanced Film Conductivity

NASA Astrophysics Data System (ADS)

Staller, Corey M.; Robinson, Zachary L.; Agrawal, Ankit; Gibbs, Stephen L.; Greenberg, Benjamin L.; Lounis, Sebastien D.; Kortshagen, Uwe R.; Milliron, Delia J.

2018-05-01

Electron conduction through bare metal oxide nanocrystal (NC) films is hindered by surface depletion regions resulting from the presence of surface states. We control the radial dopant distribution in tin-doped indium oxide (ITO) NCs as a means to manipulate the NC depletion width. We find in films of ITO NCs of equal overall dopant concentration that those with dopant-enriched surfaces show decreased depletion width and increased conductivity. Variable temperature conductivity data shows electron localization length increases and associated depletion width decreases monotonically with increased density of dopants near the NC surface. We calculate band profiles for NCs of differing radial dopant distributions and, in agreement with variable temperature conductivity fits, find NCs with dopant-enriched surfaces have narrower depletion widths and longer localization lengths than those with dopant-enriched cores. Following amelioration of NC surface depletion by atomic layer deposition of alumina, all films of equal overall dopant concentration have similar conductivity. Variable temperature conductivity measurements on alumina-capped films indicate all films behave as granular metals. Herein, we conclude that dopant-enriched surfaces decrease the near-surface depletion region, which directly increases the electron localization length and conductivity of NC films.

Tuning Nanocrystal Surface Depletion by Controlling Dopant Distribution as a Route Toward Enhanced Film Conductivity.

PubMed

Staller, Corey M; Robinson, Zachary L; Agrawal, Ankit; Gibbs, Stephen L; Greenberg, Benjamin L; Lounis, Sebastien D; Kortshagen, Uwe R; Milliron, Delia J

2018-05-09

Electron conduction through bare metal oxide nanocrystal (NC) films is hindered by surface depletion regions resulting from the presence of surface states. We control the radial dopant distribution in tin-doped indium oxide (ITO) NCs as a means to manipulate the NC depletion width. We find in films of ITO NCs of equal overall dopant concentration that those with dopant-enriched surfaces show decreased depletion width and increased conductivity. Variable temperature conductivity data show electron localization length increases and associated depletion width decreases monotonically with increased density of dopants near the NC surface. We calculate band profiles for NCs of differing radial dopant distributions and in agreement with variable temperature conductivity fits find NCs with dopant-enriched surfaces have narrower depletion widths and longer localization lengths than those with dopant-enriched cores. Following amelioration of NC surface depletion by atomic layer deposition of alumina, all films of equal overall dopant concentration have similar conductivity. Variable temperature conductivity measurements on alumina-capped films indicate all films behave as granular metals. Herein, we conclude that dopant-enriched surfaces decrease the near-surface depletion region, which directly increases the electron localization length and conductivity of NC films.

Efficient and Adaptive Methods for Computing Accurate Potential Surfaces for Quantum Nuclear Effects: Applications to Hydrogen-Transfer Reactions.

PubMed

DeGregorio, Nicole; Iyengar, Srinivasan S

2018-01-09

We present two sampling measures to gauge critical regions of potential energy surfaces. These sampling measures employ (a) the instantaneous quantum wavepacket density, an approximation to the (b) potential surface, its (c) gradients, and (d) a Shannon information theory based expression that estimates the local entropy associated with the quantum wavepacket. These four criteria together enable a directed sampling of potential surfaces that appears to correctly describe the local oscillation frequencies, or the local Nyquist frequency, of a potential surface. The sampling functions are then utilized to derive a tessellation scheme that discretizes the multidimensional space to enable efficient sampling of potential surfaces. The sampled potential surface is then combined with four different interpolation procedures, namely, (a) local Hermite curve interpolation, (b) low-pass filtered Lagrange interpolation, (c) the monomial symmetrization approximation (MSA) developed by Bowman and co-workers, and (d) a modified Shepard algorithm. The sampling procedure and the fitting schemes are used to compute (a) potential surfaces in highly anharmonic hydrogen-bonded systems and (b) study hydrogen-transfer reactions in biogenic volatile organic compounds (isoprene) where the transferring hydrogen atom is found to demonstrate critical quantum nuclear effects. In the case of isoprene, the algorithm discussed here is used to derive multidimensional potential surfaces along a hydrogen-transfer reaction path to gauge the effect of quantum-nuclear degrees of freedom on the hydrogen-transfer process. Based on the decreased computational effort, facilitated by the optimal sampling of the potential surfaces through the use of sampling functions discussed here, and the accuracy of the associated potential surfaces, we believe the method will find great utility in the study of quantum nuclear dynamics problems, of which application to hydrogen-transfer reactions and hydrogen-bonded systems is demonstrated here.

Characterization of Escherichia coli K1 colominic acid-specific murine antibodies that are cross-protective against Neisseria meningitidis groups B, C, and Y.

PubMed

Park, In Ho; Lin, Jisheng; Choi, Ji Eun; Shin, Jeon-Soo

2014-06-01

The capsular polysaccharide (PS) of Neisseria meningitidis serogroup B (NMGB) is α(2-8)-linked N-acetylneuraminic acid (Neu5Ac), which is almost identical to the O-acetylated colominic acid (CA) of Escherichia coli K1 Although E. coli K1 has long been known to elicit cross-protective antibodies against NMGB, limited information on these highly cross-reactive antibodies is available. In the present study, six new monoclonal antibodies (mAbs) specific to both E. coli K1 CA and NMGB PS were produced by immunizing Balb/c mice with E. coli K1, and their serological and molecular properties were characterized, together with 12 previously reported hybridoma mAbs. Among the bactericidal mAbs against NMGB, both HmenB5 and HmenB18, which are genetically identical though of different mouse origins, were able to kill serogroup C and Y meningococci. Based on SPR sensograms, the binding affinity of HmenB18 for PS was suggested to be associated with at least two different binding forces: the polyanionicity of Neu5Ac and an interaction with the O-acetyl groups of Neu5Ac. Molecular analysis showed that similar to most mAbs presenting a few restricted V region germline genes, the V region genes of HmenB18 were 979% and 986% identical to the closest IGHV1-1401 and IGLV15-10301 germline gene alleles, respectively, and V-D-J editing in this mAb generated an unusually long VH-CDR3 sequence (17 amino acid residues), containing one basic arginine, two hydrophobic isoleucine residues and a 'YAMDY' motif. Models of the mAb combining sites demonstrate that most of the mAbs exhibited a wide, shallow groove with a high overall positive charge, as seen in mAb735, which is specific for a polyanionic helical epitope. In contrast, the combining site of HmenB18 was shown to be wide but to present a relatively weak positive charge, consistent with the extensive recognition by HmenB18 of the various structural epitopes formed with the Neu5Ac residue and its O-acetylation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sex-specific local life-history adaptation in surface- and cave-dwelling Atlantic mollies (Poecilia mexicana).

PubMed

Riesch, Rüdiger; Reznick, David N; Plath, Martin; Schlupp, Ingo

2016-03-10

Cavefishes have long been used as model organisms showcasing adaptive diversification, but does adaptation to caves also facilitate the evolution of reproductive isolation from surface ancestors? We raised offspring of wild-caught surface- and cave-dwelling ecotypes of the neotropical fish Poecilia mexicana to sexual maturity in a 12-month common garden experiment. Fish were raised under one of two food regimes (high vs. low), and this was crossed with differences in lighting conditions (permanent darkness vs. 12:12 h light:dark cycle) in a 2 × 2 factorial design, allowing us to elucidate potential patterns of local adaptation in life histories. Our results reveal a pattern of sex-specific local life-history adaptation: Surface molly females had the highest fitness in the treatment best resembling their habitat of origin (high food and a light:dark cycle), and suffered from almost complete reproductive failure in darkness, while cave molly females were not similarly affected in any treatment. Males of both ecotypes, on the other hand, showed only weak evidence for local adaptation. Nonetheless, local life-history adaptation in females likely contributes to ecological diversification in this system and other cave animals, further supporting the role of local adaptation due to strong divergent selection as a major force in ecological speciation.

Sex-specific local life-history adaptation in surface- and cave-dwelling Atlantic mollies (Poecilia mexicana)

PubMed Central

Riesch, Rüdiger; Reznick, David N.; Plath, Martin; Schlupp, Ingo

2016-01-01

Cavefishes have long been used as model organisms showcasing adaptive diversification, but does adaptation to caves also facilitate the evolution of reproductive isolation from surface ancestors? We raised offspring of wild-caught surface- and cave-dwelling ecotypes of the neotropical fish Poecilia mexicana to sexual maturity in a 12-month common garden experiment. Fish were raised under one of two food regimes (high vs. low), and this was crossed with differences in lighting conditions (permanent darkness vs. 12:12 h light:dark cycle) in a 2 × 2 factorial design, allowing us to elucidate potential patterns of local adaptation in life histories. Our results reveal a pattern of sex-specific local life-history adaptation: Surface molly females had the highest fitness in the treatment best resembling their habitat of origin (high food and a light:dark cycle), and suffered from almost complete reproductive failure in darkness, while cave molly females were not similarly affected in any treatment. Males of both ecotypes, on the other hand, showed only weak evidence for local adaptation. Nonetheless, local life-history adaptation in females likely contributes to ecological diversification in this system and other cave animals, further supporting the role of local adaptation due to strong divergent selection as a major force in ecological speciation. PMID:26960566

Mapping of local argon impingement on a virtual surface: an insight for gas injection during FEBID

NASA Astrophysics Data System (ADS)

Wanzenboeck, H. D.; Hochleitner, G.; Mika, J.; Shawrav, M. M.; Gavagnin, M.; Bertagnolli, E.

2014-12-01

During the last decades, focused electron beam induced deposition (FEBID) has become a successful approach for direct-write fabrication of nanodevices. Such a deposition technique relies on the precursor supply to the sample surface which is typically accomplished by a gas injection system using a tube-shaped injector nozzle. This precursor injection strategy implies a position-dependent concentration gradient on the surface, which affects the geometry and chemistry of the final nanodeposit. Although simulations already proposed the local distribution of nozzle-borne gas molecules impinging on the surface, this isolated step in the FEBID process has never been experimentally measured yet. This work experimentally investigates the local distribution of impinging gas molecules on the sample plane, isolating the direct impingement component from surface diffusion or precursor depletion by deposition. The experimental setup used in this work maps and quantifies the local impinging rate of argon gas over the sample plane. This setup simulates the identical conditions for a precursor molecule during FEBID. Argon gas was locally collected with a sniffer tube, which is directly connected to a residual gas analyzer for quantification. The measured distribution of impinging gas molecules showed a strong position dependence. Indeed, a 300-µm shift of the deposition area to a position further away from the impingement center spot resulted in a 50 % decrease in the precursor impinging rate on the surface area. With the same parameters, the precursor distribution was also simulated by a Monte Carlo software by Friedli and Utke and showed a good correlation between the empirical and the simulated precursor distribution. The results hereby presented underline the importance of controlling the local precursor flux conditions in order to obtain reproducible and comparable deposition results in FEBID.

Three-dimensional localized coherent structures of surface turbulence: Model validation with experiments and further computations.

PubMed

Demekhin, E A; Kalaidin, E N; Kalliadasis, S; Vlaskin, S Yu

2010-09-01

We validate experimentally the Kapitsa-Shkadov model utilized in the theoretical studies by Demekhin [Phys. Fluids 19, 114103 (2007)10.1063/1.2793148; Phys. Fluids 19, 114104 (2007)]10.1063/1.2793149 of surface turbulence on a thin liquid film flowing down a vertical planar wall. For water at 15° , surface turbulence typically occurs at an inlet Reynolds number of ≃40 . Of particular interest is to assess experimentally the predictions of the model for three-dimensional nonlinear localized coherent structures, which represent elementary processes of surface turbulence. For this purpose we devise simple experiments to investigate the instabilities and transitions leading to such structures. Our experimental results are in good agreement with the theoretical predictions of the model. We also perform time-dependent computations for the formation of coherent structures and their interaction with localized structures of smaller amplitude on the surface of the film.

Heat and mass transfer rates during flow of dissociated hydrogen gas over graphite surface

NASA Technical Reports Server (NTRS)

Nema, V. K.; Sharma, O. P.

1986-01-01

To improve upon the performance of chemical rockets, the nuclear reactor has been applied to a rocket propulsion system using hydrogen gas as working fluid and a graphite-composite forming a part of the structure. Under the boundary layer approximation, theoretical predictions of skin friction coefficient, surface heat transfer rate and surface regression rate have been made for laminar/turbulent dissociated hydrogen gas flowing over a flat graphite surface. The external stream is assumed to be frozen. The analysis is restricted to Mach numbers low enough to deal with the situation of only surface-reaction between hydrogen and graphite. Empirical correlations of displacement thickness, local skin friction coefficient, local Nusselt number and local non-dimensional heat transfer rate have been obtained. The magnitude of the surface regression rate is found low enough to ensure the use of graphite as a linear or a component of the system over an extended period without loss of performance.

Investigation of the first-order phase transition kinetics using the method of pulsed photothermal surface deformation: radial measurements

NASA Astrophysics Data System (ADS)

Vintzentz, S. V.; Sandomirsky, V. B.

1992-09-01

An extension of the photothermal surface deformation (PTSD) method to study the macroscopic kinetics of the first-order phase transition (PTr) is given. The movement of the phase interface (PI) over a surface with a PTr locally induced in the subsurface volume by a focused laser pulse is investigated for the first time using radial measurements of the PTSD kinetics. For the known metal-to-semiconductor PTr in VO 2 (a good model system) a procedure is suggested for measuring the maximum size rsm of the "hot" (metal) phase on the surface (a parameter most difficult to determine) as well as for estimating the velocity of the PI movement over the surface, vs, and in the bulk, vb. Besides, it is shown that the PTSD method may be used to determine the "local" threshold energy E0 needed for the laser-induced PTr and the "local" latent heat L of the PTr. This demonstrates the feasibility of scanning surface E0- and L-microscopy.

Dynamic placement of plasmonic hotspots for super-resolution surface-enhanced Raman scattering.

PubMed

Ertsgaard, Christopher T; McKoskey, Rachel M; Rich, Isabel S; Lindquist, Nathan C

2014-10-28

In this paper, we demonstrate dynamic placement of locally enhanced plasmonic fields using holographic laser illumination of a silver nanohole array. To visualize these focused "hotspots", the silver surface was coated with various biological samples for surface-enhanced Raman spectroscopy (SERS) imaging. Due to the large field enhancements, blinking behavior of the SERS hotspots was observed and processed using a stochastic optical reconstruction microscopy algorithm enabling super-resolution localization of the hotspots to within 10 nm. These hotspots were then shifted across the surface in subwavelength (<100 nm for a wavelength of 660 nm) steps using holographic illumination from a spatial light modulator. This created a dynamic imaging and sensing surface, whereas static illumination would only have produced stationary hotspots. Using this technique, we also show that such subwavelength shifting and localization of plasmonic hotspots has potential for imaging applications. Interestingly, illuminating the surface with randomly shifting SERS hotspots was sufficient to completely fill in a wide field of view for super-resolution chemical imaging.

Local Solid Shape

PubMed Central

Koenderink, Jan; van Doorn, Andrea

2015-01-01

Local solid shape applies to the surface curvature of small surface patches—essentially regions of approximately constant curvatures—of volumetric objects that are smooth volumetric regions in Euclidean 3-space. This should be distinguished from local shape in pictorial space. The difference is categorical. Although local solid shape has naturally been explored in haptics, results in vision are not forthcoming. We describe a simple experiment in which observers judge shape quality and magnitude of cinematographic presentations. Without prior training, observers readily use continuous shape index and Casorati curvature scales with reasonable resolution. PMID:27648217

Integration of Heterogenous Digital Surface Models

NASA Astrophysics Data System (ADS)

Boesch, R.; Ginzler, C.

2011-08-01

The application of extended digital surface models often reveals, that despite an acceptable global accuracy for a given dataset, the local accuracy of the model can vary in a wide range. For high resolution applications which cover the spatial extent of a whole country, this can be a major drawback. Within the Swiss National Forest Inventory (NFI), two digital surface models are available, one derived from LiDAR point data and the other from aerial images. Automatic photogrammetric image matching with ADS80 aerial infrared images with 25cm and 50cm resolution is used to generate a surface model (ADS-DSM) with 1m resolution covering whole switzerland (approx. 41000 km2). The spatially corresponding LiDAR dataset has a global point density of 0.5 points per m2 and is mainly used in applications as interpolated grid with 2m resolution (LiDAR-DSM). Although both surface models seem to offer a comparable accuracy from a global view, local analysis shows significant differences. Both datasets have been acquired over several years. Concerning LiDAR-DSM, different flight patterns and inconsistent quality control result in a significantly varying point density. The image acquisition of the ADS-DSM is also stretched over several years and the model generation is hampered by clouds, varying illumination and shadow effects. Nevertheless many classification and feature extraction applications requiring high resolution data depend on the local accuracy of the used surface model, therefore precise knowledge of the local data quality is essential. The commercial photogrammetric software NGATE (part of SOCET SET) generates the image based surface model (ADS-DSM) and delivers also a map with figures of merit (FOM) of the matching process for each calculated height pixel. The FOM-map contains matching codes like high slope, excessive shift or low correlation. For the generation of the LiDAR-DSM only first- and last-pulse data was available. Therefore only the point distribution can be used to derive a local accuracy measure. For the calculation of a robust point distribution measure, a constrained triangulation of local points (within an area of 100m2) has been implemented using the Open Source project CGAL. The area of each triangle is a measure for the spatial distribution of raw points in this local area. Combining the FOM-map with the local evaluation of LiDAR points allows an appropriate local accuracy evaluation of both surface models. The currently implemented strategy ("partial replacement") uses the hypothesis, that the ADS-DSM is superior due to its better global accuracy of 1m. If the local analysis of the FOM-map within the 100m2 area shows significant matching errors, the corresponding area of the triangulated LiDAR points is analyzed. If the point density and distribution is sufficient, the LiDAR-DSM will be used in favor of the ADS-DSM at this location. If the local triangulation reflects low point density or the variance of triangle areas exceeds a threshold, the investigated location will be marked as NODATA area. In a future implementation ("anisotropic fusion") an anisotropic inverse distance weighting (IDW) will be used, which merges both surface models in the point data space by using FOM-map and local triangulation to derive a quality weight for each of the interpolation points. The "partial replacement" implementation and the "fusion" prototype for the anisotropic IDW make use of the Open Source projects CGAL (Computational Geometry Algorithms Library), GDAL (Geospatial Data Abstraction Library) and OpenCV (Open Source Computer Vision).

Understanding of surface pit formation mechanism of GaN grown in MOCVD based on local thermodynamic equilibrium assumption

NASA Astrophysics Data System (ADS)

Zhi-Yuan, Gao; Xiao-Wei, Xue; Jiang-Jiang, Li; Xun, Wang; Yan-Hui, Xing; Bi-Feng, Cui; De-Shu, Zou

2016-06-01

Frank’s theory describes that a screw dislocation will produce a pit on the surface, and has been evidenced in many material systems including GaN. However, the size of the pit calculated from the theory deviates significantly from experimental result. Through a careful observation of the variations of surface pits and local surface morphology with growing temperature and V/III ratio for c-plane GaN, we believe that Frank’s model is valid only in a small local surface area where thermodynamic equilibrium state can be assumed to stay the same. If the kinetic process is too vigorous or too slow to reach a balance, the local equilibrium range will be too small for the center and edge of the screw dislocation spiral to be kept in the same equilibrium state. When the curvature at the center of the dislocation core reaches the critical value 1/r 0, at the edge of the spiral, the accelerating rate of the curvature may not fall to zero, so the pit cannot reach a stationary shape and will keep enlarging under the control of minimization of surface energy to result in a large-sized surface pit. Project supported by the National Natural Science Foundation of China (Grant Nos. 11204009 and 61204011) and the Beijing Municipal Natural Science Foundation, China (Grant No. 4142005).

Surface dynamics and mechanics in liquid crystal polymer coatings

NASA Astrophysics Data System (ADS)

Liu, Danqing; Broer, Dirk J.

2015-03-01

Based on liquid crystal networks we developed `smart' coatings with responsive surface topographies. Either by prepatterning or by the formation of self-organized structures they can be switched on and off in a pre-designed manner. Here we provide an overview of our methods to generate coatings that form surface structures upon the actuation by light. The coating oscillates between a flat surface and a surface with pre-designed 3D micro-patterns by modulating a light source. With recent developments in solid state lighting, light is an attractive trigger medium as it can be integrated in a device for local control or can be used remotely for flood or localized exposure. The basic principle of formation of surface topographies is based on the change of molecular organization in ordered liquid crystal polymer networks. The change in order leads to anisotropic dimensional changes with contraction along the director and expansion to the two perpendicular directions and an increase in volume by the formation of free volume. These two effects work in concert to provide local expansion and contraction in the coating steered by the local direction of molecular orientation. The surface deformation, expressed as the height difference between the activated regions and the non-activated regions divided by the initial film thickness, is of the order of 20%. Switching occurs immediately when the light is switched `on' and `off' and takes several tens of seconds.

Relationships between substrate, surface characteristics, and vegetation in an initial ecosystem

NASA Astrophysics Data System (ADS)

Biber, P.; Seifert, S.; Zaplata, M. K.; Schaaf, W.; Pretzsch, H.; Fischer, A.

2013-12-01

We investigated surface and vegetation dynamics in the artificial initial ecosystem "Chicken Creek" (Lusatia, Germany) in the years 2006-2011 across a wide spectrum of empirical data. We scrutinized three overarching hypotheses concerning (1) the relations between initial geomorphological and substrate characteristics with surface structure and terrain properties, (2) the effects of the latter on the occurrence of grouped plant species, and (3) vegetation density effects on terrain surface change. Our data comprise and conflate annual vegetation monitoring results, biennial terrestrial laser scans (starting in 2008), annual groundwater levels, and initially measured soil characteristics. The empirical evidence mostly confirms the hypotheses, revealing statistically significant relations for several goal variables: (1) the surface structure properties, local rill density, local relief energy and terrain surface height change; (2) the cover of different plant groups (annual, herbaceous, grass-like, woody, Fabaceae), and local vegetation height; and (3) terrain surface height change showed significant time-dependent relations with a variable that proxies local plant biomass. Additionally, period specific effects (like a calendar-year optimum effect for the occurrence of Fabaceae) were proven. Further and beyond the hypotheses, our findings on the spatiotemporal dynamics during the system's early development grasp processes which generally mark the transition from a geo-hydro-system towards a bio-geo-hydro system (weakening geomorphology effects on substrate surface dynamics, while vegetation effects intensify with time), where pure geomorphology or substrate feedbacks are changing into vegetation-substrate feedback processes.

Development of a laser-induced heat flux technique for measurement of convective heat transfer coefficients in a supersonic flowfield

NASA Technical Reports Server (NTRS)

Porro, A. Robert; Keith, Theo G., Jr.; Hingst, Warren R.; Chriss, Randall M.; Seablom, Kirk D.

1991-01-01

A technique is developed to measure the local convective heat transfer coefficient on a model surface in a supersonic flow field. The technique uses a laser to apply a discrete local heat flux at the model test surface, and an infrared camera system determines the local temperature distribution due to heating. From this temperature distribution and an analysis of the heating process, a local convective heat transfer coefficient is determined. The technique was used to measure the load surface convective heat transfer coefficient distribution on a flat plate at nominal Mach numbers of 2.5, 3.0, 3.5, and 4.0. The flat plate boundary layer initially was laminar and became transitional in the measurement region. The experimental results agreed reasonably well with theoretical predictions of convective heat transfer of flat plate laminar boundary layers. The results indicate that this non-intrusive optical measurement technique has the potential to obtain high quality surface convective heat transfer measurements in high speed flowfields.

Do galaxy global relationships emerge from local ones? The SDSS IV MaNGA surface mass density-metallicity relation

NASA Astrophysics Data System (ADS)

Barrera-Ballesteros, Jorge K.; Heckman, Timothy M.; Zhu, Guangtun B.; Zakamska, Nadia L.; Sánchez, Sebastian F.; Law, David; Wake, David; Green, Jenny E.; Bizyaev, Dmitry; Oravetz, Daniel; Simmons, Audrey; Malanushenko, Elena; Pan, Kaike; Roman Lopes, Alexandre; Lane, Richard R.

2016-12-01

We present the stellar surface mass density versus gas metallicity (Σ*-Z) relation for more than 500 000 spatially resolved star-forming resolution elements (spaxels) from a sample of 653 disc galaxies included in the SDSS IV MaNGA survey. We find a tight relation between these local properties, with higher metallicities as the surface density increases. This relation extends over three orders of magnitude in the surface mass density and a factor of 4 in metallicity. We show that this local relationship can simultaneously reproduce two well-known properties of disc galaxies: their global mass-metallicity relationship and their radial metallicity gradients. We also find that the Σ*-Z relation is largely independent of the galaxy's total stellar mass and specific star formation rate (sSFR), except at low stellar mass and high sSFR. These results suggest that in the present-day universe local properties play a key role in determining the gas-phase metallicity in typical disc galaxies.

Amplified all-optical polarization phase modulator assisted by a local surface plasmon in Au-hybrid CdSe quantum dots.

PubMed

Kyhm, Kwangseuk; Je, Koo-Chul; Taylor, Robert A

2012-08-27

We propose an amplified all-optical polarization phase modulator assisted by a local surface plasmon in Au-hybrid CdSe quantum dots. When the local surface plasmon of a spherical Au quantum dot is in resonance with the exciton energy level of a CdSe quantum dot, a significant enhancement of the linear and nonlinear refractive index is found in both the real and imaginary terms via the interaction with the dipole field of the local surface plasmon. Given a gating pulse intensity, an elliptical polarization induced by the phase retardation is described in terms of elliptical and rotational angles. In the case that a larger excitation than the bleaching intensity is applied, the signal light can be amplified due to the presence of gain in the CdSe quantum dot. This enables a longer propagation of the signal light relative to the metal loss, resulting in more feasible polarization modulation.

Exploring new topography-based subgrid spatial structures for improving land surface modeling

DOE PAGES

Tesfa, Teklu K.; Leung, Lai-Yung Ruby

2017-02-22

Topography plays an important role in land surface processes through its influence on atmospheric forcing, soil and vegetation properties, and river network topology and drainage area. Land surface models with a spatial structure that captures spatial heterogeneity, which is directly affected by topography, may improve the representation of land surface processes. Previous studies found that land surface modeling, using subbasins instead of structured grids as computational units, improves the scalability of simulated runoff and streamflow processes. In this study, new land surface spatial structures are explored by further dividing subbasins into subgrid structures based on topographic properties, including surface elevation,more » slope and aspect. Two methods (local and global) of watershed discretization are applied to derive two types of subgrid structures (geo-located and non-geo-located) over the topographically diverse Columbia River basin in the northwestern United States. In the global method, a fixed elevation classification scheme is used to discretize subbasins. The local method utilizes concepts of hypsometric analysis to discretize each subbasin, using different elevation ranges that also naturally account for slope variations. The relative merits of the two methods and subgrid structures are investigated for their ability to capture topographic heterogeneity and the implications of this on representations of atmospheric forcing and land cover spatial patterns. Results showed that the local method reduces the standard deviation (SD) of subgrid surface elevation in the study domain by 17 to 19 % compared to the global method, highlighting the relative advantages of the local method for capturing subgrid topographic variations. The comparison between the two types of subgrid structures showed that the non-geo-located subgrid structures are more consistent across different area threshold values than the geo-located subgrid structures. Altogether the local method and non-geo-located subgrid structures effectively and robustly capture topographic, climatic and vegetation variability, which is important for land surface modeling.« less

Exploring new topography-based subgrid spatial structures for improving land surface modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tesfa, Teklu K.; Leung, Lai-Yung Ruby

Topography plays an important role in land surface processes through its influence on atmospheric forcing, soil and vegetation properties, and river network topology and drainage area. Land surface models with a spatial structure that captures spatial heterogeneity, which is directly affected by topography, may improve the representation of land surface processes. Previous studies found that land surface modeling, using subbasins instead of structured grids as computational units, improves the scalability of simulated runoff and streamflow processes. In this study, new land surface spatial structures are explored by further dividing subbasins into subgrid structures based on topographic properties, including surface elevation,more » slope and aspect. Two methods (local and global) of watershed discretization are applied to derive two types of subgrid structures (geo-located and non-geo-located) over the topographically diverse Columbia River basin in the northwestern United States. In the global method, a fixed elevation classification scheme is used to discretize subbasins. The local method utilizes concepts of hypsometric analysis to discretize each subbasin, using different elevation ranges that also naturally account for slope variations. The relative merits of the two methods and subgrid structures are investigated for their ability to capture topographic heterogeneity and the implications of this on representations of atmospheric forcing and land cover spatial patterns. Results showed that the local method reduces the standard deviation (SD) of subgrid surface elevation in the study domain by 17 to 19 % compared to the global method, highlighting the relative advantages of the local method for capturing subgrid topographic variations. The comparison between the two types of subgrid structures showed that the non-geo-located subgrid structures are more consistent across different area threshold values than the geo-located subgrid structures. Altogether the local method and non-geo-located subgrid structures effectively and robustly capture topographic, climatic and vegetation variability, which is important for land surface modeling.« less

4D Infant Cortical Surface Atlas Construction using Spherical Patch-based Sparse Representation.

PubMed

Wu, Zhengwang; Li, Gang; Meng, Yu; Wang, Li; Lin, Weili; Shen, Dinggang

2017-09-01

The 4D infant cortical surface atlas with densely sampled time points is highly needed for neuroimaging analysis of early brain development. In this paper, we build the 4D infant cortical surface atlas firstly covering 6 postnatal years with 11 time points (i.e., 1, 3, 6, 9, 12, 18, 24, 36, 48, 60, and 72 months), based on 339 longitudinal MRI scans from 50 healthy infants. To build the 4D cortical surface atlas, first , we adopt a two-stage groupwise surface registration strategy to ensure both longitudinal consistency and unbiasedness. Second , instead of simply averaging over the co-registered surfaces, a spherical patch-based sparse representation is developed to overcome possible surface registration errors across different subjects. The central idea is that, for each local spherical patch in the atlas space, we build a dictionary, which includes the samples of current local patches and their spatially-neighboring patches of all co-registered surfaces, and then the current local patch in the atlas is sparsely represented using the built dictionary. Compared to the atlas built with the conventional methods, the 4D infant cortical surface atlas constructed by our method preserves more details of cortical folding patterns, thus leading to boosted accuracy in registration of new infant cortical surfaces.

Optical properties of plasmonic nanostructures: Theory & experiments

NASA Astrophysics Data System (ADS)

Bala Krishna, Juluri

Metal nanoparticles and thin films enable localization of electromagnetic energy in the form of localized surface plasmon resonances (LSPR) and propagating surface plasmons respectively. This research field, also known as plasmonics, involves understanding and fabricating innovative nanostructures designed to manage and utilize localized light in the nanoscale. Advances in plasmonics will facilitate innovation in sensing, biomedical engineering, energy harvesting and nanophotonic devices. In this thesis, three aspects of plasmonics are studied: 1) active plasmonic systems using charge-induced plasmon shifts (CIPS) and plasmon-molecule resonant coupling; 2) scalable solutions to fabricate large electric field plasmonic nanostructures; and 3) controlling the propagation of designer surface plasmons (DSPs) using parabolic graded media. The full potential of plasmonics can be realized with active plasmonic devices which provide tunable plasmon resonances. The work reported here develops both an understanding for and realization of various mechanisms to achieve tunable plasmonic systems. First, we show that certain nanoparticle geometries and material compositions enable large CIPS. Second, we propose and investigate systems which exhibit coupling between molecular and plasmonic resonances where energy splitting is observed due to interactions between plasmons and molecules. Large electric field nanostructures have many promising applications in the areas of surface enhanced Raman spectroscopy, higher harmonic light generation, and enhanced uorescence. High throughput techniques that utilize simple nanofabrication are essential their advancement. We contribute to this effort by using a salting-out quenching technique and colloidal lithography to fabricate nanodisc dimers and cusp nanostructures that allow localization of large electric fields, and are comparable to structures fabricated by conventional lithography/milling techniques. Designer surface plasmons (DSPs) are surface waves that are localized to the interface between a structured perfect electric conductor (PEC) surface and dielectric medium. Terahertz (THz) DSPs excited on microscale structured PEC are localized in the out-of-plane direction, with negligible in-plane localization. We addressed this problem by subjecting DSPs to a parabolic graded-index structure. Lateral confinement such as focusing, collimation, and waveguiding of DSPs is demonstrated. Such control will pave the way towards THz energy concentration, diffusion, guiding, and beam aperture modifcation.

Effects of Local and Systemic Zoledronic Acid Application on Titanium Implant Osseointegration: An Experimental Study Conducted on Two Surface Types.

PubMed

Dundar, Serkan; Yaman, Ferhan; Gecor, Orhan; Cakmak, Omer; Kirtay, Mustafa; Yildirim, Tuba Talo; Karaman, Tahir; Benlidayi, Mehmet Emre

2017-06-01

The aim of this study was to evaluate the effects of local and systemic zoledronic acid (ZA) applications on titaniumoksit ceramic blasted (TiO-CB)- and sandblasted large acid-grit (SLA)-surfaced titanium implant osseointegration. Twelve New Zealand White rabbits were used in the study, divided into 6 groups: the TiO-CB (TiO-CB-CNT) (n = 2) and SLA (SLA-CNT) (n = 2) control groups in which TiO-CB- and SLA-surfaced titanium implants were surgically inserted into rabbit tibias but no treatment was applied; the TiO-CB (TiO-CB-LZA) (n = 2) and SLA (SLA-LZA) (n = 2) local ZA groups in which 1 mL of normal saline solution containing 2 mg of ZA was injected into sockets and after this the implants were integrated; and the TiO-CB (TiO-CB-SZA) (n = 2) and SLA (SLA-SZA) (n = 2) systemic ZA groups in which a single infusion of 0.1 mg/kg of ZA was administered during surgical implant insertion. Following a period of osseointegration, bone implant contact (BIC) was recorded as a proportion of the total implant surface length in direct contact with the bone. Results of this study indicate that BIC was greater in the systemic ZA application groups than in the local ZA application groups, and BIC was greater in the local ZA groups than in the controls. Statistically significant differences in BIC were not detected between the TiO-CB- and SLA-surfaced implants in all the groups. Furthermore, this study did not reveal significant differences between the 2 types of surfaces due to similar average roughness values. Overall, systemic ZA application was found to be more effective in increasing BIC than local ZA application based on the results obtained by testing 2 implant surfaces.

Surface-enhanced localized surface plasmon resonance biosensing of avian influenza DNA hybridization using subwavelength metallic nanoarrays

NASA Astrophysics Data System (ADS)

Kim, Shin Ae; Byun, Kyung Min; Kim, Kyujung; Jang, Sung Min; Ma, Kyungjae; Oh, Youngjin; Kim, Donghyun; Kim, Sung Guk; Shuler, Michael L.; Kim, Sung June

2010-09-01

We demonstrated enhanced localized surface plasmon resonance (SPR) biosensing based on subwavelength gold nanoarrays built on a thin gold film. Arrays of nanogratings (1D) and nanoholes (2D) with a period of 200 nm were fabricated by electron-beam lithography and used for the detection of avian influenza DNA hybridization. Experimental results showed that both nanoarrays provided significant sensitivity improvement and, especially, 1D nanogratings exhibited higher SPR signal amplification compared with 2D nanohole arrays. The sensitivity enhancement is associated with changes in surface-limited reaction area and strong interactions between bound molecules and localized plasmon fields. Our approach is expected to improve both the sensitivity and sensing resolution and can be applicable to label-free detection of DNA without amplification by polymerase chain reaction.

Controlling the Local Electronic Properties of Si(553)-Au through Hydrogen Doping

NASA Astrophysics Data System (ADS)

Hogan, C.; Speiser, E.; Chandola, S.; Suchkova, S.; Aulbach, J.; Schäfer, J.; Meyer, S.; Claessen, R.; Esser, N.

2018-04-01

We propose a quantitative and reversible method for tuning the charge localization of Au-stabilized stepped Si surfaces by site-specific hydrogenation. This is demonstrated for Si(553)-Au as a model system by combining density functional theory simulations and reflectance anisotropy spectroscopy experiments. We find that controlled H passivation is a two-step process: step-edge adsorption drives excess charge into the conducting metal chain "reservoir" and renders it insulating, while surplus H recovers metallic behavior. Our approach illustrates a route towards microscopic manipulation of the local surface charge distribution and establishes a reversible switch of site-specific chemical reactivity and magnetic properties on vicinal surfaces.

Numerical Estimation of the Curvature of Biological Surfaces

NASA Technical Reports Server (NTRS)

Todd, P. H.

1985-01-01

Many biological systems may profitably be studied as surface phenomena. A model consisting of isotropic growth of a curved surface from a flat sheet is assumed. With such a model, the Gaussian curvature of the final surface determines whether growth rate of the surface is subharmonic or superharmonic. These properties correspond to notions of convexity and concavity, and thus to local excess growth and local deficiency of growth. In biological models where the major factors controlling surface growth are intrinsic to the surface, researchers thus gained from geometrical study information on the differential growth undergone by the surface. These ideas were applied to an analysis of the folding of the cerebral cortex, a geometrically rather complex surface growth. A numerical surface curvature technique based on an approximation to the Dupin indicatrix of the surface was developed. A metric for comparing curvature estimates is introduced, and considerable numerical testing indicated the reliability of this technique.

Turbine heat transfer

NASA Technical Reports Server (NTRS)

Rohde, J. E.

1982-01-01

Objectives and approaches to research in turbine heat transfer are discussed. Generally, improvements in the method of determining the hot gas flow through the turbine passage is one area of concern, as is the cooling air flow inside the airfoil, and the methods of predicting the heat transfer rates on the hot gas side and on the coolant side of the airfoil. More specific areas of research are: (1) local hot gas recovery temperatures along the airfoil surfaces; (2) local airfoil wall temperature; (3) local hot gas side heat transfer coefficients on the airfoil surfaces; (4) local coolant side heat transfer coefficients inside the airfoils; (5) local hot gas flow velocities and secondary flows at real engine conditions; and (6) local delta strain range of the airfoil walls.

Using the 12-lead ECG to localize the origin of ventricular and atrial tachycardias: part 1. Focal atrial tachycardia.

PubMed

Teh, Andrew W; Kistler, Peter M; Kalman, Jonathan M

2009-06-01

Focal atrial tachycardia is an unusual form of supraventricular tachycardia arising from defined anatomic locations and sites within the atria. Although recent advances in mapping technology have facilitated successful ablation, the surface ECG remains an important aid in localizing the focus. This review discusses the use of P-wave morphology on surface ECG to localize the site of focal atrial tachycardia.

Numerical Study of Nonlinear Structures of Locally Excited Marangoni Convection in the Long-Wave Approximation

NASA Astrophysics Data System (ADS)

Wertgeim, Igor I.

2018-02-01

We investigate stationary and non-stationary solutions of nonlinear equations of the long-wave approximation for the Marangoni convection caused by a localized source of heat or a surface active impurity (surfactant) in a thin horizontal layer of a viscous incompressible fluid with a free surface. The distribution of heat or concentration flux is determined by the uniform vertical gradient of temperature or impurity concentration, distorted by the imposition of a slightly inhomogeneous heating or of surfactant, localized in the horizontal plane. The lower boundary of the layer is considered thermally insulated or impermeable, whereas the upper boundary is free and deformable. The equations obtained in the long-wave approximation are formulated in terms of the amplitudes of the temperature distribution or impurity concentration, deformation of the surface, and vorticity. For a simplification of the problem, a sequence of nonlinear equations is obtained, which in the simplest form leads to a nonlinear Schrödinger equation with a localized potential. The basic state of the system, its dependence on the parameters and stability are investigated. For stationary solutions localized in the region of the surface tension inhomogeneity, domains of parameters corresponding to different spatial patterns are delineated.

Adjoint-tomography for a Local Surface Structure: Methodology and a Blind Test

NASA Astrophysics Data System (ADS)

Kubina, Filip; Michlik, Filip; Moczo, Peter; Kristek, Jozef; Stripajova, Svetlana

2017-04-01

We have developed a multiscale full-waveform adjoint-tomography method for local surface sedimentary structures with complicated interference wavefields. The local surface sedimentary basins and valleys are often responsible for anomalous earthquake ground motions and corresponding damage in earthquakes. In many cases only relatively small number of records of a few local earthquakes is available for a site of interest. Consequently, prediction of earthquake ground motion at the site has to include numerical modeling for a realistic model of the local structure. Though limited, the information about the local structure encoded in the records is important and irreplaceable. It is therefore reasonable to have a method capable of using the limited information in records for improving a model of the local structure. A local surface structure and its interference wavefield require a specific multiscale approach. In order to verify our inversion method, we performed a blind test. We obtained synthetic seismograms at 8 receivers for 2 local sources, complete description of the sources, positions of the receivers and material parameters of the bedrock. We considered the simplest possible starting model - a homogeneous halfspace made of the bedrock. Using our inversion method we obtained an inverted model. Given the starting model, synthetic seismograms simulated for the inverted model are surprisingly close to the synthetic seismograms simulated for the true structure in the target frequency range up to 4.5 Hz. We quantify the level of agreement between the true and inverted seismograms using the L2 and time-frequency misfits, and, more importantly for earthquake-engineering applications, also using the goodness-of-fit criteria based on the earthquake-engineering characteristics of earthquake ground motion. We also verified the inverted model for other source-receiver configurations not used in the inversion.

A Multi-Year Aerosol Characterization for the Greater Tehran Area Using Satellite, Surface, and Modeling Data

PubMed Central

Crosbie, Ewan; Sorooshian, Armin; Monfared, Negar Abolhassani; Shingler, Taylor; Esmaili, Omid

2014-01-01

This study reports a multi-year (2000–2009) aerosol characterization for metropolitan Tehran and surrounding areas using multiple datasets (Moderate Resolution Imaging Spectroradiometer (MODIS), Multi-angle Imaging Spectroradiometer (MISR), Total Ozone Mapping Spectrometer (TOMS), Goddard Ozone Chemistry Aerosol Radiation and Transport (GOCART), and surface and upper air data from local stations). Monthly trends in aerosol characteristics are examined in the context of the local meteorology, regional and local emission sources, and air mass back-trajectory data. Dust strongly affects the region during the late spring and summer months (May–August) when aerosol optical depth (AOD) is at its peak and precipitation accumulation is at a minimum. In addition, the peak AOD that occurs in July is further enhanced by a substantial number of seasonal wildfires in upwind regions. Conversely, AOD is at a minimum during winter; however, reduced mixing heights and a stagnant lower atmosphere trap local aerosol emissions near the surface and lead to significant reductions in visibility within Tehran. The unique meteorology and topographic setting makes wintertime visibility and surface aerosol concentrations particularly sensitive to local anthropogenic sources and is evident in the noteworthy improvement in visibility observed on weekends. Scavenging of aerosol due to precipitation is evident during the winter when aconsistent increase in surface visibility and concurrent decrease in AOD is observed in the days after rain compared with the days immediately before rain. PMID:25083295

Adsorption properties for urokinase on local diatomite surface

NASA Astrophysics Data System (ADS)

Yang, Yuxiang; Zhang, Jianbo; Yang, Weimin; Wu, Jieda; Chen, Rongsan

2003-02-01

In this paper, adsorption isotherm of urokinase on two typical local diatomites were determined at 25 °C and their surface electrical potentials (ζ), isoelectrical point values (IEP) were determined. The properties of diatomites, the relationship among diatomite structure, pore-size distribution, surface ζ and adsorption isotherm were discussed. The adsorption equation of urokinase was calculated from the adsorption isotherm. The adsorption mode of urokinase on diatomite surface was judged by the configuration function α. The relationship between the amount of adsorbed urokinase and IEP value was also discussed.

Preprocessing of region of interest localization based on local surface curvature analysis for three-dimensional reconstruction with multiresolution

NASA Astrophysics Data System (ADS)

Li, Wanjing; Schütze, Rainer; Böhler, Martin; Boochs, Frank; Marzani, Franck S.; Voisin, Yvon

2009-06-01

We present an approach to integrate a preprocessing step of the region of interest (ROI) localization into 3-D scanners (laser or stereoscopic). The definite objective is to make the 3-D scanner intelligent enough to localize rapidly in the scene, during the preprocessing phase, the regions with high surface curvature, so that precise scanning will be done only in these regions instead of in the whole scene. In this way, the scanning time can be largely reduced, and the results contain only pertinent data. To test its feasibility and efficiency, we simulated the preprocessing process under an active stereoscopic system composed of two cameras and a video projector. The ROI localization is done in an iterative way. First, the video projector projects a regular point pattern in the scene, and then the pattern is modified iteratively according to the local surface curvature of each reconstructed 3-D point. Finally, the last pattern is used to determine the ROI. Our experiments showed that with this approach, the system is capable to localize all types of objects, including small objects with small depth.

Extratropical Respones to Amazon Deforestation

NASA Astrophysics Data System (ADS)

Badger, A.; Dirmeyer, P.

2014-12-01

Land-use change (LUC) is known to impact local climate conditions through modifications of land-atmosphere interactions. Large-scale LUC, such as Amazon deforestation, could have a significant effect on the local and regional climates. The question remains as to what the global impact of large-scale LUC could be, as previous modeling studies have shown non-local responses due to Amazon deforestation. A common shortcoming in many previous modeling studies is the use of prescribed ocean conditions, which can act as a boundary condition to dampen the global response with respect to changes in the mean and variability. Using fully coupled modeling simulations with the Community Earth System Model version 1.2.0, the Amazon rainforest has been replaced with a distribution of representative tropical crops. Through the modifications of local land-atmosphere interactions, a significant change in the region, both at the surface and throughout the atmosphere, can be quantified. Accompanying these local changes are significant changes to the atmospheric circulation across all scales, thus modifying regional climates in other locales. Notable impacts include significant changes in precipitation, surface fluxes, basin-wide sea surface temperatures and ENSO behavior.

A Method of Relating General Circulation Model Simulated Climate to the Observed Local Climate. Part I: Seasonal Statistics.

NASA Astrophysics Data System (ADS)

Karl, Thomas R.; Wang, Wei-Chyung; Schlesinger, Michael E.; Knight, Richard W.; Portman, David

1990-10-01

Important surface observations such as the daily maximum and minimum temperature, daily precipitation, and cloud ceilings often have localized characteristics that are difficult to reproduce with the current resolution and the physical parameterizations in state-of-the-art General Circulation climate Models (GCMs). Many of the difficulties can be partially attributed to mismatches in scale, local topography. regional geography and boundary conditions between models and surface-based observations. Here, we present a method, called climatological projection by model statistics (CPMS), to relate GCM grid-point flee-atmosphere statistics, the predictors, to these important local surface observations. The method can be viewed as a generalization of the model output statistics (MOS) and perfect prog (PP) procedures used in numerical weather prediction (NWP) models. It consists of the application of three statistical methods: 1) principle component analysis (FICA), 2) canonical correlation, and 3) inflated regression analysis. The PCA reduces the redundancy of the predictors The canonical correlation is used to develop simultaneous relationships between linear combinations of the predictors, the canonical variables, and the surface-based observations. Finally, inflated regression is used to relate the important canonical variables to each of the surface-based observed variables.We demonstrate that even an early version of the Oregon State University two-level atmospheric GCM (with prescribed sea surface temperature) produces free-atmosphere statistics than can, when standardized using the model's internal means and variances (the MOS-like version of CPMS), closely approximate the observed local climate. When the model data are standardized by the observed free-atmosphere means and variances (the PP version of CPMS), however, the model does not reproduce the observed surface climate as well. Our results indicate that in the MOS-like version of CPMS the differences between the output of a ten-year GCM control run and the surface-based observations are often smaller than the differences between the observations of two ten-year periods. Such positive results suggest that GCMs may already contain important climatological information that can be used to infer the local climate.

Limitations of a localized surface plasmon resonance sensor on Salmonella detection

USDA-ARS?s Scientific Manuscript database

We have designed a localized surface plasmon resonance (LSPR) biosensor to perform the whole cell detection of Salmonella using gold nanoparticls fabricated by oblique angle deposition technique. The LSPR sensor showed a plasmon peak shift due to the Salmonella antigen and anti-Salmonella antibody r...

Thermal Analysis of Unusual Local-scale Features on the Surface of Vesta

NASA Technical Reports Server (NTRS)

Tosi, F.; Capria, M. T.; DeSanctis, M. C.; Capaccioni, F.; Palomba, E.; Zambon, F.; Ammannito, E.; Blewett, D. T.; Combe, J.-Ph.; Denevi, B. W.;

Neisseria gonorrhoeae PIII has a role on NG1873 outer membrane localization and is involved in bacterial adhesion to human cervical and urethral epithelial cells.

PubMed

Leuzzi, Rosanna; Nesta, Barbara; Monaci, Elisabetta; Cartocci, Elena; Serino, Laura; Soriani, Marco; Rappuoli, Rino; Pizza, Mariagrazia

2013-11-09

Protein PIII is one of the major outer membrane proteins of Neisseria gonorrhoeae, 95% identical to RmpM (reduction modifiable protein M) or class 4 protein of Neisseria meningitidis. RmpM is known to be a membrane protein associated by non-covalent bonds to the peptidoglycan layer and interacting with PorA/PorB porin complexes resulting in the stabilization of the bacterial membrane. The C-terminal domain of PIII (and RmpM) is highly homologous to members of the OmpA family, known to have a role in adhesion/invasion in many bacterial species. The contribution of PIII in the membrane architecture and its role in the interaction with epithelial cells has never been investigated. We generated a ΔpIII knock-out mutant strain and evaluated the effects of the loss of PIII expression on bacterial morphology and on outer membrane composition. Deletion of the pIII gene does not cause any alteration in bacterial morphology or sensitivity to detergents. Moreover, the expression profile of the main membrane proteins remains the same for the wild-type and knock-out strains, with the exception of the NG1873 which is not exported to the outer membrane and accumulates in the inner membrane in the ΔpIII knock-out mutant strain.We also show that purified PIII protein is able to bind human cervical and urethral cells and that the ΔpIII knock-out mutant strain has a lower ability to adhere to human cervical and urethral cells. Here we demonstrated that the PIII protein does not play a key structural role in the membrane organization of gonococcus and does not induce major effects on the expression of the main outer membrane proteins. However, in the PIII knock-out strain, the NG1873 protein is not localized in the outer membrane as it is in the wild-type strain suggesting a possible interaction of PIII with NG1873. The evidence that PIII binds to human epithelial cells derived from the female and male genital tract highlights a possible role of PIII in the virulence of gonococcus and suggests that the structural homology to OmpA is conserved also at functional level.

Excess electrons in ice: a density functional theory study.

PubMed

Bhattacharya, Somesh Kr; Inam, Fakharul; Scandolo, Sandro

2014-02-21

We present a density functional theory study of the localization of excess electrons in the bulk and on the surface of crystalline and amorphous water ice. We analyze the initial stages of electron solvation in crystalline and amorphous ice. In the case of crystalline ice we find that excess electrons favor surface states over bulk states, even when the latter are localized at defect sites. In contrast, in amorphous ice excess electrons find it equally favorable to localize in bulk and in surface states which we attribute to the preexisting precursor states in the disordered structure. In all cases excess electrons are found to occupy the vacuum regions of the molecular network. The electron localization in the bulk of amorphous ice is assisted by its distorted hydrogen bonding network as opposed to the crystalline phase. Although qualitative, our results provide a simple interpretation of the large differences observed in the dynamics and localization of excess electrons in crystalline and amorphous ice films on metals.

Screening charge localization at LiNbO{sub 3} surface with Schottky junction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagata, Takahiro, E-mail: NAGATA.Takahiro@nims.go.jp; Chikyow, Toyohiro; Kitamura, Kenji

2016-04-25

Screening charge localization was demonstrated by using a Schottky contact with LiNbO{sub 3} (LN). A Cr/LN stack structure with a 2 μm diameter hole array penetrating the Cr layer localized the screening charge of LN in the hole, although the Al/LN stack structure exhibited no surface charge localization behavior. X-ray photoelectron spectroscopy revealed that Cr formed a Schottky contact with LN, which prevents the screening charge from escaping from the hole arrays. The screening charge localization was enhanced by inserting SiO{sub 2} between the metal and LN, which moved the position of the Fermi level to mid gap.

Polychromatic microdiffraction characterization of defect gradients in severely deformed materials.

PubMed

Barabash, Rozaliya I; Ice, Gene E; Liu, Wenjun; Barabash, Oleg M

2009-01-01

This paper analyzes local lattice rotations introduced in severely deformed polycrystalline titanium by friction stir welding. Nondestructive three-dimensional (3D) spatially resolved polychromatic X-ray microdiffraction, is used to resolve the local crystal structure of the restructured surface from neighboring local structures in the sample material. The measurements reveal strong gradients of strain and geometrically necessary dislocations near the surface and illustrate the potential of polychromatic microdiffraction for the study of deformation in complex materials systems.

Strain localization parameters of AlCu4MgSi processed by high-energy electron beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lunev, A. G., E-mail: agl@ispms.ru; Nadezhkin, M. V., E-mail: mvn@ispms.ru; National Research Tomsk Polytechnic University, Tomsk, 634050

2015-10-27

The influence of the electron beam surface treatment of AlCu4MgSi on the strain localization parameters and on the critical strain value of the Portevin–Le Chatelier effect has been considered. The strain localization parameters were measured using speckle imaging of the specimens subjected to the constant strain rate uniaxial tension at a room temperature. Impact of the surface treatment on the Portevin–Le Chatelier effect has been investigated.