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1. Quantitative bacterial counts in the bone marrow of Vietnamese patients with typhoid fever

Author

Van Be Bay, P, Wain, J, Phuong, LT, Ho, VA, Hien, TT, and Parry, CM

Subjects
wc_270, Public Health, Environmental and Occupational Health, General Medicine, Salmonella typhi, wh_380, Bacterial Load, Anti-Bacterial Agents, wc_200, Infectious Diseases, Asian People, Bone Marrow, Humans, Parasitology, Typhoid Fever
Abstract

Background Bone marrow culture (BMC) is the reference standard for typhoid fever diagnosis. We studied the additional yield of BMC over blood culture (BC) and the relationship between quantitative BMC counts and severe disease. Methods Hospitalised Vietnamese patients with suspected typhoid fever were prospectively investigated with a BC, BMC, faecal culture and quantitative BMC counts. Results Salmonella typhi was isolated in 195 of 231 patients: from BC and BMC in 144 (73.8%), from BMC alone in 33 (16.9%), from BC alone in 12 (6.2%) and from faeces alone in 6 (3.1%). In 167 patients the median extracellular count of S. typhi was 2.5 cfu/mL (interquartile range [IQR] 0–10) and the intracellular count was 10.5 cfu/mL (IQR 2–42) with a ratio of 1.3 bacteria/cell (IQR 0.6–2.5). The median count of intracellular bacteria in 24 patients with severe disease was 46 bacteria/cell (IQR 9–105) compared with 6.5 bacteria/cell (IQR 2–34) in 143 with non-severe disease (p=0.005). The intracellular BMC count was negatively correlated with the peripheral white cell count and positively correlated with hepatomegaly, splenomegaly, aspartate transaminase, a positive BC and the fever clearance time following treatment with azithromycin, ofloxacin or a combination of the two. Conclusions BMC gave a moderate additional yield over BC. Intracellular BMC counts may reflect the bacterial load in typhoid fever.

Published
2022
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2. An integrated national scale SARS-CoV-2 genomic surveillance network

Author

Aanensen, DM, Abudahab, K, Adams, A, Afifi, S, Alam, MT, Alderton, A, Alikhan, N-F, Allan, J, Almsaud, M, Alrezaihi, A, Alruwaili, M, Amato, R, Andersson, M, Angyal, A, Aranday-Cortes, E, Ariani, C, Armstrong, SD, Asamaphan, P, Attwood, S, Aydin, A, Badhan, A, Baker, D, Baker, P, Balcazar, CE, Ball, J, Barton, AE, Bashton, M, Baxter, L, Beale, M, Beaver, C, Beckett, A, Beer, R, Beggs, A, Bell, A, Bellis, KL, Bentley, EG, Berriman, M, Betteridge, E, Bibby, D, Bicknell, K, Birchley, A, Black, G, Blane, B, Bloomfield, S, Bolt, F, Bonsall, DG, Bosworth, A, Bourgeois, Y, Boyd, O, Bradshaw, D, Breuer, J, Bridgewater, H, Brooks, T, Broos, A, Brown, JR, Brown, RL, Brunker, K, Bucca, G, Buck, D, Bull, M, Butcher, E, Caddy, SL, Caller, LG, Cambell, S, Carlile, M, Carmichael, S, Carrilero, L, Castellano, S, Chaloner, J, Chand, M, Chapman, MR, Chappell, J, Charles, I, Chauhan, AJ, Chawla, A, Cheng, E, Churcher, CM, Clark, G, Clark, JJ, Collins, J, Colquhoun, R, Connor, TR, Constantinidou, C, Coombes, J, Corden, S, Cottrell, S, Cowell, A, Curran, MD, Curran, T, Dabrera, G, Danesh, J, Darby, AC, De Cesare, M, Martins, LDO, De Silva, TI, Debebe, B, Dervisevic, S, Dewar, RA, Dia, M, Dorman, M, Dougan, G, Dover, L, Downing, F, Drury, E, Du Plessis, L, Dyal, PL, Eccles, R, Edwards, S, Ellaby, N, Elliott, S, Eltringham, G, Elumogo, N, Essex, S, Evans, CM, Evans, J, Nascimento, FF, Fairley, DJ, Farr, B, Feltwell, T, Ferguson, N, Filipe, ADS, Findlay, J, Forrest, LM, Forrest, S, Foulser, L, Francois, S, Fraser, C, Frost, L, Gallagher, E, Gallagher, MD, Garcia-Dorival, I, Gaskin, A, Gatica-Wilcox, B, Gavriil, A, Geidelberg, L, Gemmell, M, Gerada, A, Gifford, L, Gilbert, L, Gilmore, P, Gilroy, R, Girgis, S, Glaysher, S, Golubchik, T, Goncalves, S, Goodfellow, I, Goodwin, S, Graham, C, Graham, L, Grammatopoulos, D, Green, A, Green, LR, Greenaway, J, Gregory, R, Groves, DC, Groves, N, Guest, M, Gunson, R, Haldenby, S, Hall, G, Hamilton, WL, Han, X, Harris, KA, Harrison, EM, Hartley, C, Herrera, C, Hesketh, A, Heyburn, D, Hill, V, Hiscox, JA, Holden, M, Holmes, A, Holmes, N, Holt, GS, Hopes, R, Hosmillo, M, Houldcroft, CJ, Howson-Wells, H, Hubb, J, Hughe, J, Hughes, M, Hutchings, S, Impey, R, Iturriza-Gomara, M, Jackson, A, Jackson, B, Jackson, DK, Jahun, AS, James, K, Jamrozy, D, Jeffries, A, Jesudason, N, John, M, Johnson, J, Johnson, KJ, Johnson, N, Johnston, I, Jones, B, Jones, R, Jones, S, Jorgensen, D, Kane, L, Kay, GL, Kay, S, Keatley, J-P, Keeley, AJ, Khakh, M, Khokhar, FA, Kitchen, C, Knight, B, Kolyva, A, Kraemer, M, Kristiansen, M, Kumziene-Summerhayes, S, Kwiatkowski, D, Lackenby, A, Langford, C, Lawniczak, M, Thanh, L-V, Lee, D, Letchford, L, Li, K, Li, L, Liggett, S, Lindsey, BB, Livett, R, Lloyd, A, Lo, S, Lockhart, M, Loh, J, Loman, NJ, Loose, M, Lucaci, A, Ludden, C, Luu, L, Lyons, RA, MacIntyre-Cockett, G, MacLean, A, Mair, D, Maksimovic, J, Manley, R, Manso, C, Manson, J, Martincorena, I, Masoli, J, Mather, AE, Mbisa, T, McCluggage, K, McClure, P, McCrone, JT, McDonald, S, McHugh, MP, McKenna, JM, McMinn, L, McMurray, C, Meadows, L, Menegazzo, M, Meredith, LW, Merrick, I, Mestek-Boukhibar, L, Miah, S, Michell, S, Michelsen, ML, Molnar, Z, Moore, C, Moore, N, Morgan, M, Morgan, S, Muddyman, D, Muir, DA, Muir, P, Myers, R, Nastouli, E, Naydenova, P, Nelson, A, Nelson, C, Nelson, R, Nicholls, S, Nichols, J, Niebel, M, Niola, P, Nomikou, K, O'Grady, J, O'Toole, AN, O'Toole, E, Olateju, C, Orton, RJ, Osman, H, Ott, S, Pacchiarini, N, Padgett, D, Page, AJ, Palmer, S, Panchbhaya, YN, Pandey, S, Park, N, Parker, MD, Parkhill, J, Parr, YA, Parsons, PJ, Partridge, DG, Patel, M, Patterson, S, Payne, B, Peacock, SJ, Penrice-Randal, R, Perry, M, Platt, S, Poplawski, R, Prakash, R, Prestwood, L, Price, A, Price, JR, Puethe, C, Pybus, O, Pymont, H, Quail, M, Quick, J, Raghwani, J, Ragonnet-Cronin, M, Rahman, S, Rainbow, L, Rajatileka, S, Rambaut, A, Ramsay, M, Randell, PA, Randle, NP, Raviprakash, V, Raza, M, Silva, PR, Rey, S, Richter, A, Robertson, DL, Robinson, TI, Robson, SC, Rooke, S, Rowan, A, Rowe, W, Roy, S, Rudder, S, Ruis, C, Sang, F, Scarlett, G, Schaefer, U, Scott, C, Scott, G, Sethi, D, Shaaban, S, Shah, R, Sharma, P, Shawli, GT, Shepherd, J, Sherriff, N, Shirley, L, Sillitoe, J, Simpson, DA, Singer, JB, Siveroni, I, Smith, C, Smith, CP, Smith, DL, Smith, N, Smith, W, Smith-Palmer, A, Smollett, K, Southgate, J, Spellman, K, Spencer-Chapman, M, Sridhar, S, Stanley, R, Stark, R, Stewart, JP, Stockton, J, Stuart, C, Studholme, D, Swainston, N, Swindells, E, Taha, Y, Tariq, MA, Taylor, B, Taylor, GP, Taylor, S, Taylor-Joyce, G, Tedim, AP, Temperton, B, Templeton, KE, Thomson, EC, Thomson, NM, Thornton, A, Thurston, S, Todd, J, Tong, L, Tonkin-Hill, G, Torok, ME, Trebes, A, Trotter, AJ, Tsoleridis, T, Tucker, RM, Tutill, HJ, Underwood, A, Unnikrishnan, M, Vamos, E, Vasylyeva, T, Vattipally, S, Victoria, A, Vipond, B, Volz, EM, Wain, J, Wang, D, Warwick-Dugdale, J, Wastnedge, E, Watkins, J, Watts, J, Webber, M, Weeks, S, Weldon, D, Whitehead, M, Williams, CA, Williams, C, Williams, D, Williams, R, Williams, TC, Wise, E, Wright, V, Wyles, MD, Wyllie, S, Yakovleva, A, Yasir, M, Yeats, C, Yew, WC, Young, GR, Yu, X, and Zarebski, A

Subjects
Microbiology (medical), Scale (ratio), SARS-CoV-2, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, COVID-19 Genomics UK (COG-UK) consortiumcontact@cogconsortium.uk, C500, Genome, Viral, Genomics, Biology, C700, Microbiology, Article, Infectious Diseases, Virology, Humans, Cartography
Abstract

The Coronavirus Disease 2019 (COVID-19) Genomics UK Consortium (COG-UK) was launched in March, 2020, with £20 million support from UK Research and Innovation, the UK Department of Health and Social Care, and Wellcome Trust. The goal of this consortium is to sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for up to 230 000 patients, health-care workers, and other essential workers in the UK with COVID-19, which will help to enable the tracking of SARS-CoV-2 transmission, identify viral mutations, and integrate with health data to assess how the viral genome interacts with cofactors and consequences of COVID-19.

Published
2020
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4. Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40

Author

Stearne, MR, Palmer, SL, Hammersley, MS, Franklin, SL, Spivey, RS, Levy, JC, Tidy, CR, Bell, NJ, Steemson, J, Barrow, BA, Coster, R, Waring, K, Nolan, L, Truscott, E, Walravens, N, Cook, L, Lampard, H, Merle, C, Parker, P, McVittie, J, Draisey, I, Murchison, LE, Brunt, AHE, Williams, MJ, Pearson, DW, Petrie, XMP, Lean, MEJ, Walmsley, D, Lyall, F, Christie, E, Church, J, Thomson, E, Farrow, A, Stowers, JM, Stowers, M, McHardy, K, Patterson, N, Wright, AD, Levi, NA, Shearer, ACI, Thompson, RJW, Taylor, G, Rayton, S, Bradbury, M, Glover, A, Smyth-Osbourne, A, Parkes, C, Graham, J, England, P, Gyde, S, Eagle, C, Chakrabarti, B, Smith, J, Sherwell, J, Kohner, EM, Dornhorst, A, Doddridge, MC, Dumskyj, M, Walji, S, Sharp, P, Sleightholm, M, Vanterpool, G, Rose, C, Frost, G, Roseblade, M, Elliott, S, Forrester, S, Foster, M, Myers, K, Chapman, R, Hayes, JR, Henry, RW, Featherston, MS, Archbold, GPR, Copeland, M, Harper, R, Richardson, I, Martin, S, Davison, HA, Hadden, DR, Kennedy, L, Atkinson, AB, Culbert, AM, Hegan, C, Tennet, H, Webb, N, Robinson, I, Holmes, J, Bell, PM, McCance, DR, Rutherford, J, Nesbitt, S, Spathis, AS, Hyer, S, Nanson, ME, James, LM, Tyrell, JM, Davis, C, Strugnell, P, Booth, M, Petrie, H, Clark, D, Rice, B, Hulland, S, Barron, JL, Yudkin, JS, Gould, BJ, Singer, J, Badenock, A, Eckert, M, Alibhai, K, Marriot, E, Cox, C, Price, R, Fernandez, M, Ryle, A, Clarke, S, Wallace, G, Mehmed, E, MacFarlane, S, Greenwood, RH, Wilson, J, Denholm, MJ, Temple, RC, Whitfield, K, Johnson, F, Munroe, C, Gorick, S, Duckworth, E, Flatman, M, Rainbow, S, Borthwick, LJ, Wheatcroft, DJ, Seaman, RJ, Christie, RA, Wheatcroft, W, Musk, P, White, J, McDougal, S, Bond, M, Raniga, P, Newton, RW, Jung, RT, Roxburgh, C, Kilgallon, B, Dick, L, Waugh, N, Kilby, S, Ellington, A, Burns, J, Fox, CV, Holloway, MC, Coghill, HM, Hein, N, Fox, A, Cowan, W, Richard, M, Quested, K, Evans, SJ, Paisey, RB, Brown, NPR, Tucker, AJ, Paisey, R, Garrett, F, Hogg, J, Park, P, Williams, K, Harvey, P, Wilcocks, R, Mason, S, Frost, J, Warren, C, Rocket, P, Bower, L, Roland, JM, Brown, DJ, Youens, J, Stanton-King, K, Mungall, H, Ball, V, Maddison, W, Donnelly, D, King, S, Griffin, P, Smith, S, Church, S, Dunn, G, Wilson, A, Palmer, K, Brown, PM, Humphriss, D, Davidson, AJM, Rose, R, Armistead, L, Townsend, S, Poon, P, Peacock, IDA, Culverwell, NJC, Charlton, MH, Connolly, BPS, Peacock, J, Barrett, J, Wain, J, Beeston, W, King, G, Hill, PG, Boulton, AJM, Robertson, AM, Katoulis, V, Olukoga, A, McDonald, H, Kumar, S, Abouaesha, F, Abuaisha, B, Knowles, EA, Higgins, S, Booker, J, Sunter, J, Breislin, K, Parker, R, Raval, P, Curwell, J, Davenport, J, Shawcross, G, Prest, A, Grey, J, Cole, H, Sereviratne, C, Young, RJ, Dornan, TL, Clyne, JR, Gibson, M, O'Connell, I, Wong, LM, Wilson, SJ, Wright, KL, Wallace, C, McDowell, D, Burden, AC, Sellen, EM, Gregory, R, Roshan, M, Vaghela, N, Burden, M, Sherriff, C, Clarke, J, Grenfell, J, Tooke, JE, MacLeod, K, Searnark, C, Rammell, M, Pym, C, Stockman, J, Yeo, C, Piper, J, Leighton, L, Green, E, Hoyle, M, Jones, K, Hudson, A, James, AJ, Shore, A, Higham, A, Martin, B, and Grp, UKPDS

Subjects
General Engineering, HC Economic History and Conditions, General Earth and Planetary Sciences, General Medicine, R Medicine (General), General Environmental Science
Abstract

Objectives: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes. Design: Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through use of the within trial hazards of reaching a defined clinical end point. Use of resources driven by trial protocol and use of resources in standard clinical practice were both considered. Setting: 20 hospital based clinics in England, Scotland, and Northern Ireland. Subjects: 1148 hypertensive patients with type 2 diabetes from UK prospective diabetes study randomised to tight control of blood pressure (n=758) or less tight control (n=390). Main outcome measure: Cost effectiveness ratios based on (a) use of healthcare resources associated with tight control and less tight control and treatment of complications and (b) within trial time free from diabetes related end points, and life years gained. Results: Based on use of resources driven by trial protocol, the incremental cost effectiveness of tight control compared with less tight control was cost saving. Based on use of resources in standard clinical practice, incremental cost per extra year free from end points amounted to £1049 (costs and effects discounted at 6% per year) and £434 (costs discounted at 6% per year and effects not discounted). The incremental cost per life year gained was £720 (costs and effects discounted at 6% per year) and £291 (costs discounted at 6% per year and effects not discounted). Conclusions: Tight control of blood pressure in hypertensive patients with type 2 diabetes substantially reduced the cost of complications, increased the interval without complications and survival, and had a cost effectiveness ratio that compares favourably with many accepted healthcare programmes.

Published
1998
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5. Egg-borne infections of humans with Salmonella: not only an Enteritidis problem

Author

Threlfall, EJ, Wain, J, Peters, T, Lane, C, de Pinna, E, Little, CL, Wales, Andrew, and Davies, RH

Abstract

The principal salmonella serovar associated with infections linked to eggs and egg products in the UK, most European countries and North America is Salmonella enteritidis. However, other serovars have also been implicated in a number of egg-associated outbreaks, most notably S. typhimurium exhibiting a range of phage types. The present article reviews human egg-associated salmonellosis associated with non-S. enteritidis serovars, predominantly in the European Union (EU) but also world-wide, using information from published literature and epidemiological databases. There are also brief reviews of S. enteritidis and of mechanisms leading to egg contamination by salmonella. The numbers of egg-associated infections caused by non-S. enteritidis serovars are fairly substantial (for example 22% of outbreaks and 11.5% of more than 20,000 cases in the EU in 2008), and such infections have resulted in hospitalisations and deaths. Furthermore, in parts of the world where S. enteritidis historically has not penetrated laying hen breeding flocks, egg-related salmonellosis is a problem associated specifically with non-S. enteritidis serovars. Control measures to limit the incidence of S. enteritidis and S. typhimurium in poultry flocks are vital. It is therefore important that close surveillance of salmonellosis incidence and serovars in laying flocks is used to establish suitable biosecurity and vaccination programmes throughout EU Member States and elsewhere.

Published
2014

6. Immunological monitoring to prevent and treat sepsis

Author

Almansa R, Wain J, Tamayo E, Andaluz-Ojeda D, Martin-Loeches I, Ramirez P, and Bermejo-Martin JF

Abstract

The clinical, human and economic burden associated with sepsis is huge. Initiatives such as the Surviving Sepsis Campaign aim to effectively reduce risk of death from severe sepsis and septic shock. Nonetheless, although substantial benefits raised from the implementation of this campaign have been obtained, much work remains if we are to realise the full potential promised by this strategy. A deeper understanding of the processes leading to sepsis is necessary before we can design an effective suite of interventions. Dysregulation of the immune response to infection is acknowledged to contribute to the pathogenesis of the disease. Production of both proinflammatory and immunosuppressive cytokines is observed from the very first hours following diagnosis. In addition, hypogammaglobulinemia is often present in patients with septic shock. Moreover, levels of IgG, IgM and IgA at diagnosis correlate directly with survival. In turn, nonsurvivors have lower levels of C4 (a protein of the complement system) than the survivors. Natural killer cell counts and function also seem to have an important role in this disease. HLA-DR in the surface of monocytes and counts of CD4+CD25+ T-regulatory cells in blood could also be useful biomarkers for sepsis. At the genomic level, repression of networks corresponding to major histocompatibility complex antigen presentation is observed in septic shock. In consequence, cumulative evidence supports the potential role of immunological monitoring to guide measures to prevent or treat sepsis in a personalised and timely manner (early antibiotic administration, immunoglobulin replacement, immunomodulation). In conclusion, although diffuse and limited, current available information supports the development of large comprehensive studies aimed to urgently evaluate immunological monitoring as a tool to prevent sepsis, guide its treatment and, as a consequence, diminish the morbidity and mortality associated with this severe condition.

Published
2013

7. A multiplex single nucleotide polymorphism typing assay for detecting mutations that result in decreased fluoroquinolone susceptibility in Salmonella enterica serovars Typhi and Paratyphi A

Author

Song, Y., Roumagnac, P., Weill, F., Wain, J., Dolecek, C., Mazzoni, C., Holt, K., and Achtman, M.

Subjects
bacteria, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, complex mixtures
Abstract

Decreased susceptibility to fluoroquinolones has become a major problem for the successful therapy of human infections caused by Salmonella enterica, especially the life-threatening typhoid and paratyphoid fevers. By using Luminex xTAG beads, we developed a rapid, reliable and cost-effective multiplexed genotyping assay for simultaneously detecting 11 mutations in gyrA, gyrB and parE of S. enterica serovars Typhi and Paratyphi A that result in nalidixic acid resistance (Nal(R)) and/or decreased susceptibility to fluoroquinolones. This assay yielded unambiguous single nucleotide polymorphism calls on extracted DNA from 292 isolates of Salmonella Typhi (Nal(R) = 223 and Nal(S) = 69) and 106 isolates of Salmonella Paratyphi A (Nal(R) = 24 and Nal(S) = 82). All of the 247 Nal(R) Salmonella Typhi and Salmonella Paratyphi A isolates were found to harbour at least one of the target mutations, with GyrA Phe-83 as the most common one (143/223 for Salmonella Typhi and 18/24 for Salmonella Paratyphi A). We also identified three GyrB mutations in eight Nal(S) Salmonella Typhi isolates (six for GyrB Phe-464, one for GyrB Leu-465 and one for GyrB Asp-466), and mutations GyrB Phe-464 and GyrB Asp-466 seem to be related to the decreased ciprofloxacin susceptibility phenotype in Salmonella Typhi. This assay can also be used directly on boiled single colonies. The assay presented here would be useful for clinical and reference laboratories to rapidly screen quinolone-resistant isolates of Salmonella Typhi and Salmonella Paratyphi A, and decipher the underlying genetic changes for epidemiological purposes.

Published
2010

8. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

Author

Turner, RC, Holman, RR, Cull, CA, Stratton, IM, Matthews, DR, Frighi, V, Manley, SE, Neil, A, McElroy, K, Wright, D, Kohner, E, Fox, C, Hadden, D, Mehta, Z, Smith, A, Nugent, Z, Peto, R, Adlel, AI, Mann, JI, Bassett, PA, Oakes, SF, Dornan, TL, Aldington, S, Lipinski, H, Collum, R, Harrison, K, MacIntyre, C, Skinner, S, Mortemore, A, Nelson, D, Cockley, S, Levien, S, Bodsworth, L, Willox, R, Biggs, T, Dove, S, Beattie, E, Gradwell, M, Staples, S, Lam, R, Taylor, F, Leung, L, Carter, RD, Brownlee, SM, Fisher, KE, Islam, K, Jelfs, R, Williams, PA, Williams, FA, Sutton, PJ, Ayres, A, Logie, LJ, Lovatt, C, Evans, MA, Stowell, LA, Ross, I, Kennedy, IA, Croft, D, Keen, AH, Rose, C, Raikou, M, Fletcher, AE, Bulpitt, C, Battersby, C, Yudkin, JS, Stevens, R, Stearn, MR, Palmer, SL, Hammersley, MS, Franklin, SL, Spivey, RS, Levy, JC, Tidy, CR, Bell, NJ, Steemson, J, Barrow, BA, Coster, R, Waring, K, Nolan, L, Truscott, E, Walravens, N, Cook, L, Lampard, H, Merle, C, Parker, P, McVittie, J, Draisey, I, Murchison, LE, Brunt, AHE, Williams, MJ, Pearson, DW, Petrie, XMP, Lean, MEJ, Walmsley, D, Lyall, F, Christie, E, Church, J, Thomson, E, Farrow, A, Stowers, JM, Stowers, M, McHardy, K, Patterson, N, Wright, AD, Levi, NA, Shearer, ACI, Thompson, RJW, Taylor, G, Rayton, S, Bradbury, M, Glover, A, Smyth-Osbourne, A, Parkes, C, Graham, J, England, P, Gyde, S, Eagle, C, Chakrabarti, B, Smith, J, Sherwell, J, Oakley, NW, Whitehead, MA, Hollier, GP, Pilkington, T, Simpson, J, Anderson, M, Martin, S, Kean, J, Rice, B, Rolland, A, Nisbet, J, Kohner, EM, Dornhorst, A, Doddridge, MC, Dumskyij, M, Walji, S, Sharp, P, Sleightholm, M, Vanterpool, G, Frost, G, Roseblade, M, Elliott, S, Forrester, S, Foster, M, Myers, K, Chapman, R, Hayes, JR, Henry, RW, Featherston, MS, Archbold, GPR, Copeland, M, Harper, R, Richardson, I, Davison, HA, Alexander, L, Scarpello, JHB, Shiers, DE, Tucker, RJ, Worthington, JRH, Angris, S, Bates, A, Walton, J, Teasdale, M, Browne, J, Stanley, S, Davis, BA, Strange, RC, Hadden, DR, Kennedy, L, Atkinson, AB, Bell, PM, McCance, DR, Rutherford, J, Culbert, AM, Hegan, C, Tennet, H, Webb, N, Robinson, I, Holmes, J, Nesbitt, S, Spathis, AS, Hyer, S, Nanson, ME, James, LM, Tyrell, JM, Davis, C, Strugnell, P, Booth, M, Petrie, H, Clark, D, Hulland, S, Barron, JL, Gould, BC, Singer, J, Badenoch, A, McGregor, M, Isenberg, L, Eckert, M, Alibhai, K, Marriot, E, Cox, C, Price, R, Fernandez, M, Ryle, A, Clarke, S, Wallace, G, Mehmed, E, Lankester, JA, Howard, E, Waite, A, MacFarlane, S, Greenwood, RH, Wilson, J, Denholm, MJ, Temple, RC, Whitfield, K, Johnson, F, Munroe, C, Gorick, S, Duckworth, E, Fatman, M, Rainbow, S, Borthwick, L, Wheatcroft, DJ, Seaman, RJ, Christie, RA, Wheatcroft, W, Musk, P, White, J, McDougal, S, Bond, M, Raniga, P, Day, JL, Doshi, MJ, Wilson, JG, Howard-Williams, JR, Humphreys, H, Graham, A, Hicks, K, Hexman, S, Bayliss, P, Pledger, D, Newton, RW, Jung, RT, Roxburgh, C, Kilgallon, B, Dick, L, Waugh, N, Kilby, S, Ellingford, A, Burns, J, Fox, CV, Holloway, MC, Coghill, HM, Hein, N, Fox, A, Cowan, W, Richard, M, Quested, K, Evans, SJ, Paisey, RB, Brown, NPR, Tucker, AJ, Paisey, R, Garrett, F, Hogg, J, Park, P, Williams, K, Harvey, P, Wilcocks, R, Mason, S, Frost, J, Warren, C, Rocket, P, Bower, L, Roland, JM, Brown, DJ, Youens, J, Stanton-King, K, Mungall, H, Ball, V, Maddison, W, Donnelly, D, King, S, Griffin, P, Smith, S, Church, S, Dunn, G, Wilson, A, Palmer, K, Brown, PM, Humphriss, D, Davidson, AJM, Rose, R, Armistead, L, Townsend, S, Poon, P, Peacock, IDA, Culverwell, NJC, Charlton, MH, Connolly, BPS, Peacock, J, Barrett, J, Wain, J, Beeston, W, King, G, Hill, PG, Boulton, AJM, Robertson, AM, Katoulis, V, Olukoga, A, McDonald, H, Kumar, S, Abouaesha, F, Abuaisha, B, Knowles, EA, Higgins, S, Booker, J, Sunter, J, Breislin, K, Parker, R, Raval, P, Curwell, J, Davenport, H, Shawcross, G, Prest, A, Grey, J, Cole, H, Sereviratne, C, Young, RJ, Clyne, JR, Gibson, M, O'Connell, I, Wong, LM, Wilson, SJ, Wright, KL, Wallace, C, McDowell, D, Burden, AC, Sellen, EM, Gregory, R, Roshan, M, Vaghela, N, Burden, M, Sherriff, C, Mansingh, S, Clarke, J, Grenfell, J, Tooke, JE, MacLeod, K, Seamark, C, Rammell, M, Pym, C, Stockman, J, Yeo, C, Piper, J, Leighton, L, Green, E, Hoyle, M, Jones, K, Hudson, A, James, AJ, Shore, A, Higham, A, Martin, B, Neil, HAW, Butterfield, WJH, Doll, WRS, Eastman, R, Ferris, FR, Kurinij, N, McPherson, K, Mahler, RF, Meade, TW, Shafer, G, Watkins, PJ, Keen, H, Siegel, D, Betteridge, DJ, Cohen, RD, Currie, D, Darbyshire, J, Forrester, JV, Guppy, T, Johnston, DG, McGuire, A, Murphy, M, el-Nahas, AM, Pentecost, B, Spiegelhalter, D, Alberti, KGMM, Denton, R, Home, PD, Howell, S, Jarrett, JR, Marks, V, Marmot, M, Ward, JD, and Grp, UKPDS

Subjects
General Medicine
Published
1998

9. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group

Author

Stearne, MR, Palmer, SL, Hammersley, MS, Franklin, SL, Spivey, RS, Levy, JC, Tidy, CR, Bell, NJ, Steemson, J, Barrow, BA, Coster, R, Waring, K, Nolan, J, Truscott, E, Walravens, N, Cook, L, Lampard, H, Merle, C, Parker, P, McVittie, J, Draisey, I, Murchison, LE, Brunt, AHE, Williams, MJ, Pearson, DW, Petrie, XMP, Lean, MEJ, Walmsley, D, Lyall, MJ, Christie, E, Church, J, Thomson, E, Farrow, A, Stowers, JM, Stowers, M, McHardy, K, Patterson, N, Wright, AD, Levi, NA, Shearer, ACI, Thompson, RJW, Taylor, G, Rayton, S, Bradbury, M, Glover, A, Smyth-Osbourne, A, Parkes, C, Graham, J, England, P, Gyde, S, Eagle, C, Chakrabarti, B, Smith, J, Sherwell, J, Kohner, EM, Dornhurst, A, Doddridge, MC, Dumskyj, M, Walji, S, Sharp, P, Sleightholm, M, Vanterpool, G, Rose, C, Frost, G, Roseblade, M, Elliott, S, Forrester, S, Foster, M, Myers, K, Chapman, R, Hayes, JR, Henry, RW, Featherston, MS, Archbold, GPR, Copeland, M, Harper, R, Richardson, I, Martin, S, Davison, HA, Hadden, DR, Kennedy, L, Atkinson, AB, Culbert, AM, Hegan, C, Tennet, H, Webb, N, Robinson, I, Holmes, J, Bell, PM, McCance, DR, Rutherford, J, Nesbitt, S, Spathis, AS, Hyer, S, Nanson, ME, James, LM, Tyrell, JM, Davis, C, Strugnell, P, Booth, M, Petrie, H, Clark, D, Rice, B, Hulland, S, Barron, JL, Yudkin, JS, Gould, BJ, Singer, J, Badenock, A, Eckert, M, Alibhai, K, Marriot, E, Cox, C, Price, R, Fernandez, M, Ryle, A, Clarke, S, Wallace, G, Mehmed, E, MacFarlane, S, Greenwood, RH, Wilson, J, Denholm, MJ, Temple, RC, Whitfield, K, Johnson, F, Munroe, C, Gorick, S, Duckworth, E, Flatman, M, Rainbow, S, Borthwick, LJ, Wheatcroft, DJ, Seaman, RJ, Christie, RA, Wheatcroft, W, Musk, P, White, J, McDougal, S, Bond, M, Raniga, P, Newton, RW, Jung, RT, Roxburgh, C, Kilgallon, B, Dick, L, Waugh, N, Kilby, S, Ellingford, A, Burns, J, Fox, CV, Holloway, MC, Coghill, HM, Hein, N, Fox, A, Cowan, W, Richard, M, Quested, K, Evans, SJ, Paisey, RB, Brown, NPR, Tucker, AJ, Paisey, R, Garrett, F, Hogg, J, Park, P, Williams, K, Harvey, P, Wilcocks, R, Mason, S, Frost, J, Warren, C, Rocket, P, Bower, L, Roland, JM, Brown, DJ, Youens, J, Stanton-King, K, Mungall, H, Ball, V, Maddison, W, Donnelly, D, King, S, Griffin, P, Smith, S, Church, S, Dunn, G, Wilson, A, Palmer, K, Brown, PM, Humphriss, D, Davidson, AJM, Rose, R, Armistead, L, Townsend, S, Poon, P, Peacock, IDA, Culverwell, NJC, Charlton, MH, Connolly, BPS, Peacock, J, Barrett, J, Wain, J, Beeston, W, King, G, Hill, PG, Boulton, AJM, Robertson, AM, Katoulis, V, Olukoga, A, McDonald, H, Kumar, S, Abouaesha, F, Abuaisha, B, Knowles, EA, Higgins, S, Booker, J, Sunter, J, Breislin, K, Parker, R, Raval, P, Curwell, J, Davenport, H, Shawcross, G, Prest, A, Grey, J, Cole, H, Sereviratne, C, Young, RJ, Dornan, TL, Clyne, JR, Gibson, M, O'Connell, I, Wong, LM, Wilson, SJ, Wright, KL, Wallace, C, McDowell, D, Burden, AC, Sellen, EM, Gregory, R, Roshan, M, Vaghela, N, Burden, M, Sherriff, C, Clarke, J, Grenfell, J, Tooke, JE, MacLeod, K, Searnark, C, Rammell, M, Pym, C, Stockman, J, Yeo, C, Piper, J, Leighton, L, Green, E, Hoyle, M, Jones, K, Hudson, A, James, AJ, Shore, A, Higham, A, Martin, B, and Grp, USPDS

Abstract

OBJECTIVE: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. DESIGN: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of

Published
1998

10. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group

Author

Stearne, MR, Palmer, SL, Hammersley, MS, Franklin, SL, Spivey, RS, Levy, JC, Tidy, CR, Bell, NJ, Steemson, J, Barrow, BA, Coster, R, Waring, K, Nolan, L, Truscott, E, Walravens, N, Cook, BL, Lampard, H, Merle, C, Parker, P, McVittie, J, Draisey, I, Murchison, LE, Brunt, AHE, Williams, MJ, Pearson, DW, Petrie, XMP, Lean, MEJ, Walmsley, D, Lyall, F, Christie, E, Church, J, Thomson, E, Farrow, A, Stowers, JM, Stowers, M, McHardy, K, Patterson, N, Wright, AD, Levi, NA, Shearer, AGI, Thompson, RJW, Taylor, G, Rayton, S, Bradbury, M, Glover, A, Smyth-Osbourne, A, Parkes, C, Graham, J, England, P, Gyde, S, Eagle, C, Chakrabarti, B, Smith, J, Sherwell, J, Kohner, EM, Dornhorst, A, Doddridge, MC, Dumskyj, M, Walji, S, Sharp, P, Sleightholm, M, Vanterpool, G, Rose, C, Frost, G, Roseblade, M, Elliott, S, Forrester, S, Foster, M, Myers, K, Chapman, R, Hayes, JR, Henry, TW, Featherston, MS, Archbold, GPR, Copeland, M, Harper, R, Richardson, I, Martin, S, Davison, HA, Hadden, DR, Kennedy, L, Atkinson, AB, Culbert, AM, Hegan, C, Tennet, H, Webb, N, Robinson, I, Holmes, J, Bell, PM, McCance, DR, Rutherford, J, Nesbitt, S, Spathis, AS, Hyer, S, Nanson, ME, James, JM, Tyrell, JM, Davis, C, Strugnell, P, Booth, M, Petrie, H, Clark, D, Rice, B, Hulland, S, Barron, JL, Yudkin, JS, Gould, BJ, Singer, J, Badenock, A, Eckert, M, Alibhai, K, Marriot, E, Cox, C, Price, R, Fernandez, M, Ryle, A, Clarke, S, Wallace, G, Mehmed, E, MacFarlane, S, Greenwood, RH, Wilson, J, Denholm, MJ, Temple, RC, Whitfield, K, Johnson, F, Munroe, C, Gorick, S, Duckworth, E, Flatman, M, Rainbow, S, Borthwick, LJ, Wheatcroft, DJ, Seaman, RJ, Christie, RA, Wheatcroft, W, Musk, P, White, J, McDougal, S, Bond, M, Raniga, P, Newton, RW, Jung, RT, Roxburgh, C, Kilgallon, B, Dick, L, Waugh, N, Kilby, S, Ellingford, A, Burns, J, Fox, CV, Holloway, MC, Coghill, HM, Hein, N, Fox, A, Cowan, W, Richard, M, Quested, K, Evans, SJ, Paisey, RB, Brown, NPR, Tucker, AJ, Paisey, R, Garrett, F, Hogg, J, Park, P, Williams, K, Harvey, P, Wilcocks, R, Mason, S, Frost, J, Warren, C, Rocket, P, Bower, L, Roland, JM, Brown, DJ, Youens, J, Stanton-King, K, Mungall, H, Ball, V, Maddison, W, Donnelly, D, King, S, Griffin, P, Smith, S, Church, S, Dunn, G, Wilson, A, Palmer, K, Brown, PM, Humphriss, D, Davidson, AJM, Rose, R, Armistead, L, Townsend, S, Poon, P, Peacock, IDA, Culverwell, NJC, Charlton, MH, Connolly, BPS, Peacock, J, Barrett, J, Wain, J, Beeston, W, King, G, Hill, PG, Boulton, AJM, Robertson, AM, Katoulis, V, Olukoga, A, McDonald, H, Kumar, S, Abouaesha, F, Abuaisha, B, Knowles, EA, Higgins, S, Booker, J, Sunter, J, Breislin, K, Parker, R, Raval, P, Curwell, J, Davenport, H, Shawcross, G, Prest, A, Grey, J, Cole, H, Sereviratne, C, Young, RJ, Dornan, TL, Clyne, JR, Gibson, M, O'Connell, I, Wong, LM, Wilson, SJ, Wright, KL, Wallace, C, McDowell, D, Burden, AC, Sellen, EM, Gregory, R, Roshan, M, Vaghela, N, Burden, M, Sherriff, C, Clarke, J, Grenfell, J, Tooke, JE, MacLeod, K, Searnark, C, Rammell, M, Pym, C, Stockman, J, Yeo, C, Piper, J, Leighton, L, Green, E, Hoyle, M, Jones, K, Hudson, A, James, AJ, Shore, A, Higham, A, Martin, B, and Grp, USPDS

Subjects
cardiovascular diseases, circulatory and respiratory physiology
Abstract

OBJECTIVE: To determine whether tight control of blood pressure with either a beta blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes. DESIGN: Randomised controlled trial comparing an angiotensin converting enzyme inhibitor (captopril) with a beta blocker (atenolol) in patients with type 2 diabetes aiming at a blood pressure of =300 mg/l (5% and 9%). The proportion of patients with hypoglycaemic attacks was not different between groups, but mean weight gain in the atenolol group was greater (3.4 kg v 1.6 kg). CONCLUSION: Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications. This study provided no evidence that either drug has any specific beneficial or deleterious effect, suggesting that blood pressure reduction in itself may be more important than the treatment used.

Published
1998

11. The In-vitro susceptibilities of toxigenic Corynebacterium diphtheriae isolated between 1992 and 1996 in Viet nam

Author

Parry, C. M., Hoa, N. T. T., Wain, J., Kneen, R., Dung, N. M., Giao, P. N., Hien, T. T., and Nicholas White

Abstract

The in-vitro activities of 12 antibiotics against 88 toxigenic strains of C.diphtheriae isolated from children with clinical diphtheria between 1992 and 19% were determined by agar dilution. All isolates were susceptible to penicillin, ampicillin, cefuroxime, ceftriaxone, ciprofloxacin and gentamicin. 27/88 (31%) isolates were resistant to one or more of the other antibiotics including tetracycline in 21/88 (24%), erythromycin and azithromycin in 13/88 (15%), chloramphenicol in 7/88 (8%), trimethoprim in 3/88 (3%) and rifampicin in 1/88(1%). 14/88 isolates were resistant to several antibiotics [TetREryR (7), TetRChlorR (2), TetREryR ChlorR (2) and TetRChlorRTrimRRifR (1)]. The emergence of resistance to multiple antibiotics in C.diphtheriae is of concern.

Published
1997

16. Value of a single-tube Widal test in diagnosis of typhoid fever in Vietnam

Author

Parry, C. M., Nguyen Thi Tuyet, H., Diep, T. S., Wain, J., Chinh, N. T., Vinh, H., Hien, T. T., Nicholas White, and Farrar, J. J.

Abstract

The diagnostic value of an acute-phase single-tube Widal test for suspected typhoid fever was evaluated with 2,000 Vietnamese patients admitted to an infectious disease referral hospital between 1993 and 1998. Test patients had suspected typhoid fever and a blood culture positive for Salmonella typhi (n= 1,400) or Salmonella paratyphi A (n = 45). Control patients had a febrile illness for which another cause was confirmed (malaria [n = 103], dengue [n = 76], or bacteremia due to another microorganism [n = 156] or tetanus (n = 265). An O-agglutinin titer of >/=100 was found in 18% of the febrile controls and 7% of the tetanus patients. Corresponding values for H agglutinins were 8 and 1%, respectively. The O-agglutinin titer was >/=100 in 83% of the blood culture-positive typhoid fever cases, and the H-agglutinin titer was >/=100 in 67%. The disease prevalence in investigated patients in this hospital was 30.8% (95% confidence interval, 26.8 to 35.1%); at this prevalence, an elevated level of H agglutinins gave better positive predictive values for typhoid fever than did O agglutinins. With a cutoff titer of >/=200 for O agglutinin or >/=100 for H agglutinin, the Widal test would diagnose correctly 74% of the blood culture-positive cases of typhoid fever. However, 14% of the positive results would be false-positive, and 10% of the negative results would be false-negative. The Widal test can be helpful in the laboratory diagnosis of typhoid fever in Vietnam if interpreted with care.

18. Quantitation of bacteria in blood of typhoid fever patients and relationship between counts and clinical features, transmissibility, and antibiotic resistance

Author

Wain, J., Diep, T. S., Ho, V. A., Walsh, A. M., Hoa, N. T. T., Parry, C. M., and Nicholas White

Abstract

Salmonella typhi was isolated from 369 and Salmonella paratyphi A was isolated from 6 of 515 Vietnamese patients with suspected enteric fever. Compared with conventional broth culture of blood, direct plating of the buffy coat had a diagnostic sensitivity of 99.5% (95% confidence interval [CI], 97.1 to 100%). Blood bacterial counts were estimated by the pour plate method. The median S. typhi count in blood was 1 CFU/ml (range

20. National outbreak of Salmonella Enteritidis phage type 14b in England, September to December 2009: case-control study

Author

Janmohamed, K., Dominik Zenner, Little, C., Lane, C., Wain, J., Charlett, A., Adak, B., and Morgan, D.

Subjects
Adult, Male, Restaurants, Adolescent, Diet, Vegetarian, Eggs, Middle Aged, Disease Outbreaks, Young Adult, England, Salmonella enteritidis, Case-Control Studies, Humans, Female, Salmonella Food Poisoning, Child, Salmonella Phages, Aged, Retrospective Studies
Abstract

We conducted an unmatched retrospective case–control study to investigate an upsurge of non-travel-related sporadic cases of infection with Salmonella enterica subsp. enterica serotype Enteritidis phage type 14b with antimicrobial resistance to nalidixic acid and partial resistance to ciprofloxacin (S. Enteritidis PT 14b NxCp(L)) that was reported in England from 1 September to 31 December 2009. We analysed data from 63 cases and 108 controls to determine whether cases had the same sources of infection as those found through investigation of 16 concurrent local foodborne outbreaks in England and Wales. Multivariable logistic regression analysis adjusting for age and sex identified food consumption at restaurants serving Chinese or Thai cuisine (odds ratio (OR): 4.4; 95% CI: 1.3–14.8; p=0.02), egg consumed away from home (OR: 5.1; 95% CI: 1.3–21.2; p=0.02) and eating vegetarian foods away from home (OR: 14.6; 95% CI: 2.1–99; p=0.006) as significant risk factors for infection with S. Enteritidis PT 14b NxCp(L). These findings concurred with those from the investigation of the16 outbreaks, which identified the same Salmonella strain in eggs from a specified source outside the United Kingdom. The findings led to a prohibition of imports from this source, in order to control the outbreak.

21. The use of whole genome sequencing for the analysis of isolates belonging to the bacterial genus Salmonella

Author

Pearce, M, Grant, K, Chattaway, M, Alikhan, N, Langridge, G, Lauer, A, Sintchenko, V, Colles, F, Wain, J, and Maiden, M

Subjects
Epidemiology, Salmonella, Speciation, Genomics, Gastrointestinal system, Microbiology
Abstract

The global burden of disease from Salmonella infections is substantial and the increase of trade and travel across borders presented very real challenges, such as the investigation of multi-country outbreaks. The primary aim of this thesis was to examine WGS for the analysis of Salmonella, especially in regard to the public health applications of sequencing. A review was conducted in Chapter Two to establish the impact of whole genome sequencing on public health to date. The analyses undertaken here were primarily conducted by upscaling the MLST- approach. In Chapter Three cgMLST was shown to be highly congruent with SNP-based approaches for outbreak investigations. The use of cgMLST enabled easier communication across borders as it was reference free and readily available online. In Chapter Four the current core scheme was shown to be problematic for whole genus analyses. A new scheme was therefore developed and used for the identification and analysis of isolates from across the genus. This included the identification of novel subspecies and the reclassification of subspecies IIIa as a separate species – S. arizonae, as demonstrated in Chapter Five. This in turn enabled more accurate reporting of the salmonellae. WGS can also be used to characterise datasets of related organisms as demonstrated through an analysis of serovar Enteritidis isolates from New South Wales, as shown in Chapter Six. This analysis identified differences between regions and countries in serovar Enteritidis strains and their AMR profiles. This work provided an overview of the utility of WGS for public health purposes and expanded the current understanding of the molecular epidemiology of Salmonella.

Published
2022

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