Browsing by Author "Karen H. Keddy"

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    An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid
    (2016-01-01) Vanessa K. Wong; Stephen Baker; Thomas R. Connor; Derek Pickard; Andrew J. Page; Jayshree Dave; Niamh Murphy; Richard Holliman; Armine Sefton; Michael Millar; Zoe A. Dyson; Gordon Dougan; Kathryn E. Holt; Julian Parkhill; Robert A. Kingsley; Nicholas R. Thomson; Jacqueline A. Keane; James Hadfield; Elizabeth J. Klemm; Simon R. Harris; Amy K. Cain; Samuel Kariuki; Chinyere Okoro; Calman A. MacLennan; Nga Tran Vu Thieu; Duy Pham Thanh; Corinne Thompson; Christiane Dolecek; James I. Campbell; Guy Thwaites; Jeremy Farrar; Paul N. Newton; David Dance; Paul Turner; E. Kim Mulholland; Jane Hawkey; David J. Edwards; Nicholas A. Feasey; François Xavier Weill; Simon Le Hello; Peter J. Hart; Robert F. Breiman; Robert S. Onsare; Conall H. Watson; W. John Edmunds; Melita A. Gordon; Robert S. Heyderman; Chisomo Msefula; Jan Jacobs; Octavie Lunguya; Jose A. Chabalgoity; Mike Kama; Kylie Jenkins; Shanta Dutta; Florian Marks; Josefina Campos; Stephen Obaro; Karen H. Keddy; Anthony M. Smith; Christopher M. Parry; Abhilasha Karkey; Sabina Dongol; Buddha Basnyat; Amit Arjyal; Muriel Dufour; Don Bandaranayake; Wellcome Trust Sanger Institute; Addenbrooke's Hospital; UCL; Nuffield Department of Clinical Medicine; London School of Hygiene & Tropical Medicine; Cardiff University; Public Health England; Barts and The London NHS Trust; University of Melbourne; Bio21 Molecular Science and Biotechnology Institute; Liverpool School of Tropical Medicine; Quadram Institute Bioscience; Institut Pasteur, Paris; University of Birmingham; Kenya Medical Research Institute; Centers for Disease Control and Prevention; Emory Global Health Institute; University of Liverpool; University of Malawi College of Medicine; Prins Leopold Instituut voor Tropische Geneeskunde; KU Leuven; National Institute for Biomedical Research; University Hospital of Kinshasa; Universidad de la Republica Instituto de Higiene; Ministry of Health; null; National Institute of Cholera and Enteric Diseases India; International Vaccine Institute, Seoul; ANLIS-Carlos G Malbran Institute; University of Nebraska Medical Center; University of Abuja; Bingham University; University of Witwatersrand; Nagasaki University; Oxford University Clinical Research Unit; Murdoch Children's Research Institute; Institute of Environmental Science and Research Limited (ESR); ESR - Kenepuru Science Centre; Samoa Ministry of Health; Organisation Mondiale de la Sante; Hasanuddin University; Mahosot Hospital; Tupua Tamasese Meaole Hospital; Mahidol University; Chelsea and Westminster Hospital; University of Otago; Angkor Hospital for Children; University of Cambridge; St Augustine's Hospital
    © The Author(s) 2016. The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.
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    Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa
    (2016-09-22) Vanessa K. Wong; Kathryn E. Holt; Chinyere Okoro; Stephen Baker; Derek J. Pickard; Florian Marks; Andrew J. Page; Grace Olanipekun; Huda Munir; Roxanne Alter; Paul D. Fey; Nicholas A. Feasey; François Xavier Weill; Simon Le Hello; Peter J. Hart; Samuel Kariuki; Robert F. Breiman; Melita A. Gordon; Robert S. Heyderman; Jan Jacobs; Octavie Lunguya; Chisomo Msefula; Calman A. MacLennan; Karen H. Keddy; Anthony M. Smith; Robert S. Onsare; Elizabeth De Pinna; Satheesh Nair; Ben Amos; Gordon Dougan; Stephen Obaro; Julian Parkhill; Robert A. Kingsley; Nicholas R. Thomson; Jacqueline A. Keane; Jane Hawkey; David J. Edwards; Zoe A. Dyson; Simon R. Harris; Amy K. Cain; James Hadfield; Elizabeth J. Klemm; Conall H. Watson; W. John Edmunds; Nga Tran Vu Thieu; Mike Kama; Kylie Jenkins; Shanta Dutta; Josefina Campos; Corinne Thompson; Christiane Dolecek; Christopher M. Parry; Abhilasha Karkey; E. Kim Mulholland; James I. Campbell; Sabina Dongol; Buddha Basnyat; Amit Arjyal; Muriel Dufour; Don Bandaranayake; Take N. Toleafoa; Shalini Pravin Singh; Mochammad Hatta; Lupeoletalalelei Isaia; Wellcome Trust Sanger Institute; Addenbrooke's Hospital; Bio21 Molecular Science and Biotechnology Institute; University of Melbourne; UCL; Nuffield Department of Clinical Medicine; London School of Hygiene & Tropical Medicine; International Vaccine Institute, Seoul; International Foundation Against Infectious Diseases in Nigeria (IFAIN); Aminu Kano Teaching Hospital; University of Nebraska Medical Center; Liverpool School of Tropical Medicine; Institut Pasteur, Paris; University of Birmingham; St George's University of London; Kenya Medical Research Institute; Centers for Disease Control and Prevention; Emory Global Health Institute; University of Liverpool; University of Malawi College of Medicine; Prins Leopold Instituut voor Tropische Geneeskunde; KU Leuven; National Institute for Biomedical Research; University Hospital of Kinshasa; University of Witwatersrand; Public Health England; St Augustine's Hospital; University of Abuja; Bingham University; Quadram Institute Bioscience; Universidad de la Republica Instituto de Higiene; Ministry of Health; Fiji Health Sector Support Program; National Institute of Cholera and Enteric Diseases India; ANLIS-Carlos G Malbran Institute; Nagasaki University; Oxford University Clinical Research Unit; Murdoch Children's Research Institute; Institute of Environmental Science and Research Limited (ESR); ESR - Kenepuru Science Centre; Samoa Ministry of Health; Organisation Mondiale de la Sante; Hasanuddin University; Tupua Tamasese Meaole Hospital; Mahidol University; Angkor Hospital for Children; University of Otago; Cardiff University; Barts and The London NHS Trust; University of Cambridge
    © 2016 Public Library of Science. All rights reserved. Background: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid.
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    Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter-and intracontinental transmission events
    (2015-05-27) Vanessa K. Wong; Stephen Baker; Derek J. Pickard; Julian Parkhill; Andrew J. Page; Nicholas A. Feasey; Robert A. Kingsley; Nicholas R. Thomson; Jacqueline A. Keane; François Xavier Weill; David J. Edwards; Jane Hawkey; Simon R. Harris; Alison E. Mather; Amy K. Cain; James Hadfield; Peter J. Hart; Nga Tran Vu Thieu; Elizabeth J. Klemm; Dafni A. Glinos; Robert F. Breiman; Conall H. Watson; Samuel Kariuki; Melita A. Gordon; Robert S. Heyderman; Chinyere Okoro; Jan Jacobs; Octavie Lunguya; W. John Edmunds; Chisomo Msefula; Jose A. Chabalgoity; Mike Kama; Kylie Jenkins; Shanta Dutta; Florian Marks; Josefina Campos; Corinne Thompson; Stephen Obaro; Calman A. Maclennan; Christiane Dolecek; Karen H. Keddy; Anthony M. Smith; Christopher M. Parry; Abhilasha Karkey; E. Kim Mulholland; James I. Campbell; Sabina Dongol; Buddha Basnyat; Muriel Dufour; Don Bandaranayake; Take Toleafoa Naseri; Shalini Pravin Singh; Mochammad Hatta; Paul Newton; Robert S. Onsare; Lupeoletalalei Isaia; David Dance; Viengmon Davong; Guy Thwaites; Lalith Wijedoru; John A. Crump; Elizabeth De Pinna; Satheesh Nair; Eric J. Nilles; Duy Pham Thanh; Paul Turner; Sona Soeng; Mary Valcanis; Joan Powling; Karolina Dimovski; Geoff Hogg; Jeremy Farrar; Kathryn E. Holt; Wellcome Trust Sanger Institute; Addenbrooke's Hospital; University of Oxford; Nuffield Department of Clinical Medicine; London School of Hygiene & Tropical Medicine; Liverpool School of Tropical Medicine; Quadram Institute Bioscience; Institut Pasteur, Paris; Bio21 Molecular Science and Biotechnology Institute; University of Melbourne; University of Birmingham; Kenya Medical Research Institute; Centers for Disease Control and Prevention; Emory Global Health Institute; University of Liverpool; University of Malawi College of Medicine; Prins Leopold Instituut voor Tropische Geneeskunde; KU Leuven; National Institute for Biomedical Research; University Hospital of Kinshasa; Universidad de la Republica Instituto de Higiene; Ministry of Health; Fiji Health Sector Support Program; National Institute of Cholera and Enteric Diseases India; International Vaccine Institute, Seoul; Administracion Nacional de Laboratorios E Institutos de Salud Dr. Carlos G. Malbran; University of Nebraska Medical Center; University of Abuja; Bingham University; Novartis Vaccines Institute for Global Health; University of Witwatersrand; Nagasaki University; Murdoch Children's Research Institute; ESR - Environmental Science and Research; Samoa Ministry of Health; Organisation Mondiale de la Sante; Hasanuddin University; Mahosot Hospital; Tupua Tamasese Meaole Hospital; Mahidol University; Chelsea and Westminster Hospital; University of Otago; Public Health England; Angkor Hospital for Children
    © 2015 Nature America, Inc. All rights reserved. The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.