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5 results on '"Harrison, O. B."'

1. Ribosomal multilocus sequence typing: universal characterization of bacteria from domain to strain

Author

Jolley, K. A., Bliss, C. M., Bennett, J. S., Bratcher, H. B., Brehony, C., Colles, F. M., Wimalarathna, Helen, Harrison, O. B., Sheppard, S. K., Cody, A. J., Maiden, M. C. J., Jolley, K. A., Bliss, C. M., Bennett, J. S., Bratcher, H. B., Brehony, C., Colles, F. M., Wimalarathna, Helen, Harrison, O. B., Sheppard, S. K., Cody, A. J., and Maiden, M. C. J.

Abstract

No single genealogical reconstruction or typing method currently encompasses all levels of bacterial diversity, from domain to strain. We propose ribosomal multilocus sequence typing (rMLST), an approach which indexes variation of the 53 genes encoding the bacterial ribosome protein subunits (rps genes), as a means of integrating microbial genealogy and typing. As with multilocus sequence typing (MLST), rMLST employs curated reference sequences to identify gene variants efficiently and rapidly. The rps loci are ideal targets for a universal characterization scheme as they are: (i) present in all bacteria; (ii) distributed around the chromosome; and (iii) encode proteins which are under stabilizing selection for functional conservation. Collectively, the rps loci exhibit variation that resolves bacteria into groups at all taxonomic and most typing levels, providing significantly more resolution than 16S small subunit rRNA gene phylogenies. A web-accessible expandable database, comprising whole-genome data from more than 1900 bacterial isolates, including 28 draft genomes assembled de novo from the European Bioinformatics Institute (EBI) sequence read archive, has been assembled. The rps gene variation catalogued in this database permits rapid and computationally non-intensive identification of the phylogenetic position of any bacterial sequence at the domain, phylum, class, order, family, genus, species and strain levels. The groupings generated with rMLST data are consistent with current nomenclature schemes and independent of the clustering algorithm used. This approach is applicable to the other domains of life, potentially providing a rational and universal approach to the classification of life that is based on one of its fundamental features, the translation mechanism.

Published
2012

3. Analysis of Pathogen-Host Cell Interactions in Purpura Fulminans: Expression of Capsule, Type IV Pili, and PorA by Neisseria meningitidisIn Vivo

Author

Harrison, O. B., Robertson, B. D., Faust, S. N., Jepson, M. A., Goldin, R. D., Levin, M., and Heyderman, R. S.

Abstract

ABSTRACTThe pattern of meningococcal surface structure expression in different microenvironments following bloodstream invasion in vivo is not known. We used immunohistochemistry to determine the expression of capsule, type IV pili, and PorA by meningococci residing in the skin lesions of children with purpura fulminans. All the skin biopsy samples showed evidence of thrombosis and, frequently, a perivascular inflammatory cell infiltrate consisting of neutrophils (elastase positive) and monocytes/macrophages (CD68 positive). Modified Gram staining revealed 20 to over 100 gram-negative diplococci in each 4-μm-thick section, usually grouped into microcolonies. Immunoperoxidase staining demonstrated that the invading meningococci expressed PorA, capsule, and type IV pilin. Expression of these antigens was not restricted to any particular environment and was found in association with meningococci located in leukocytes, small blood vessels, and the dermal interstitium. Confocal laser scanning microscopy demonstrated coexpression of pilin and capsule by numerous microcolonies. However, there was some discordance in capsule and pilin expression within the microcolonies, suggesting phase variation. The strategy employed in this study will be helpful in investigating invasive bacterial diseases where antigenic and phase variation has a significant impact on virulence and on vaccine design.

Published
2002
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4. Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study [corrected].

Author

Daugla, D M, Gami, J P, Gamougam, K, Naibei, N, Mbainadji, L, Narbé, M, Toralta, J, Kodbesse, B, Ngadoua, C, Coldiron, M E, Fermon, F, Page, A-L, Djingarey, M H, Hugonnet, S, Harrison, O B, Rebbetts, L S, Tekletsion, Y, Watkins, E R, Hill, D, and Caugant, D A

Subjects
*CARRIER state (Communicable diseases), *DEMOGRAPHY, *EPIDEMICS, *IMMUNIZATION, *PUBLIC health surveillance, *RESEARCH funding, *DISEASE incidence, *MENINGOCOCCAL vaccines, *GRAM-negative aerobic bacteria, *DIAGNOSIS, *MENINGOCOCCAL infections, *PREVENTION
Abstract

Background: A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic.Methods: We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods.Findings: Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046-0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001).Interpretation: PSA-TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established.Funding: The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères. [ABSTRACT FROM AUTHOR]

Published
2014
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5. Dysfunction of endothelial protein C activation in severe meningococcal sepsis.

Author

Faust SN, Levin M, Harrison OB, Goldin RD, Lockhart MS, Kondaveeti S, Laszik Z, Esmon CT, and Heyderman RS

Subjects
Antithrombin III, Antithrombins metabolism, Bacteremia, Biopsy, Case-Control Studies, Child, Preschool, Down-Regulation, Endothelium chemistry, Endothelium diagnostic imaging, Endothelium metabolism, Humans, IgA Vasculitis etiology, Meningococcal Infections complications, Microscopy, Electron, Neisseria meningitidis, Peptide Hydrolases blood, Protein S metabolism, Receptors, Cell Surface blood, Skin diagnostic imaging, Skin pathology, Thrombomodulin blood, Ultrasonography, Blood Coagulation Factors, IgA Vasculitis pathology, Meningococcal Infections metabolism, Meningococcal Infections pathology, Protein C metabolism, Receptors, Cell Surface analysis, Skin chemistry, Thrombomodulin analysis
Abstract

Background: Impairment of the protein C anticoagulation pathway is critical to the thrombosis associated with sepsis and to the development of purpura fulminans in meningococcemia. We studied the expression of thrombomodulin and the endothelial protein C receptor in the dermal microvasculature of children with severe meningococcemia and purpuric or petechial lesions., Methods: We assessed the integrity of the endothelium and the expression of thrombomodulin and the endothelial protein C receptor in biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis (median age, 41 months), as compared with control skin-biopsy specimens., Results: The expression of endothelial thrombomodulin and of the endothelial protein C receptor was lower in the patients with meningococcal sepsis than in the controls, both in vessels with thrombosis and in vessels without thrombosis. On electron microscopical examination, the endothelial cells were generally intact in both thrombosed and nonthrombosed vessels. Plasma thrombomodulin levels in the children with meningococcal sepsis (median, 6.4 ng per liter) were higher than those in the controls (median, 3.6 ng per liter; P=0.002). Plasma levels, protein C antigen, protein S antigen, and antithrombin antigen were lower than those in the controls. In two patients treated with unactivated protein C concentrate, activated protein C was undetectable at the time of admission, and plasma levels remained low., Conclusions: In severe meningococcal sepsis, protein C activation is impaired, a finding consistent with down-regulation of the endothelial thrombomodulin-endothelial protein C receptor pathway.

Published
2001
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