title: Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.
abstract: 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.
authors.affiliation: 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Department of Microbiology, Addenbrooke's Hospital, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.
authors.forename: Vanessa K
authors.initials: VK
authors.lastname: Wong
authors.affiliation: 1] Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. [2] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK. [3] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Pickard
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Julian
authors.identifier: 0000000270695958
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Page
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Feasey
authors.affiliation: 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Institute of Food Research, Norwich Research Park, Norwich, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
authors.affiliation: 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Keane
authors.affiliation: Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Paris, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Weill
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Edwards
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia. [2] Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Hawkey
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Simon R
authors.identifier: 0000000315126194
authors.initials: SR
authors.lastname: Harris
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mather
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Cain
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hadfield
authors.affiliation: Institute of Biomedical Research, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hart
authors.affiliation: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Nga Tran Vu
authors.initials: NT
authors.lastname: Thieu
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Klemm
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Dafni A
authors.initials: DA
authors.lastname: Glinos
authors.affiliation: 1] Kenya Medical Research Institute (KEMRI), Nairobi, Kenya. [2] Centers for Disease Control and Prevention, Atlanta, Georgia, USA. [3] Emory Global Health Institute, Atlanta, Georgia, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Breiman
authors.affiliation: Centre for the Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Conall H
authors.initials: CH
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authors.affiliation: 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kariuki
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Melita A
authors.initials: MA
authors.lastname: Gordon
authors.affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Chinyere
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authors.affiliation: 1] Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. [2] Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Jacobs
authors.affiliation: 1] National Institute for Biomedical Research, Kinshasa, Democratic Republic of the Congo. [2] University Hospital of Kinshasa, Kinshasa, Democratic Republic of the Congo.
authors.forename: Octavie
authors.initials: O
authors.lastname: Lunguya
authors.affiliation: Centre for the Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: W John
authors.initials: WJ
authors.lastname: Edmunds
authors.affiliation: 1] Malawi-Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi. [2] Microbiology Department, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Chisomo
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authors.affiliation: Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Montevideo, Uruguay.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Chabalgoity
authors.affiliation: Ministry of Health, Suva, Fiji.
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authors.affiliation: Fiji Health Sector Support Program, Suva, Fiji.
authors.forename: Kylie
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authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
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authors.lastname: Dutta
authors.affiliation: International Vaccine Institute, Department of Epidemiology, Seoul, Republic of Korea.
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authors.affiliation: Enteropathogen Division, Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) Carlos G. Malbran Institute, Buenos Aires, Argentina.
authors.forename: Josefina
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authors.affiliation: 1] Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. [2] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
authors.forename: Corinne
authors.initials: C
authors.lastname: Thompson
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authors.forename: Stephen
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authors.affiliation: 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Institute of Biomedical Research, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK. [3] Novartis Vaccines Institute for Global Health, Siena, Italy.
authors.forename: Calman A
authors.initials: CA
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authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.affiliation: Centre for Enteric Diseases, National Institute for Communicable Diseases, Division in the National Health Laboratory Service, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Karen H
authors.initials: KH
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authors.affiliation: Centre for Enteric Diseases, National Institute for Communicable Diseases, Division in the National Health Laboratory Service, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Smith
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authors.forename: Christopher M
authors.initials: CM
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authors.affiliation: Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
authors.forename: Abhilasha
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authors.affiliation: 1] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. [2] Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
authors.forename: E Kim
authors.initials: EK
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authors.affiliation: 1] Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. [2] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
authors.forename: James I
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authors.affiliation: Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
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authors.affiliation: Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
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authors.affiliation: Enteric and Leptospira Reference Laboratory, Institute of Environmental Science and Research, Ltd. (ESR), Porirua, New Zealand.
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authors.affiliation: National Centre for Biosecurity and Infectious Disease, Institute of Environmental Science and Research, Porirua, New Zealand.
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authors.affiliation: Samoa Ministry of Health, Apia, Samoa.
authors.forename: Take Toleafoa
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authors.affiliation: National Influenza Center, World Health Organization, Center for Communicable Disease Control, Suva, Fiji.
authors.forename: Shalini Pravin
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authors.affiliation: Department of Microbiology, Hasanuddin University, Makassar, Indonesia.
authors.forename: Mochammad
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authors.affiliation: 1] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK. [2] Lao Oxford Mahosot Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.
authors.forename: Paul
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authors.affiliation: Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
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authors.forename: Lupeoletalalei
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authors.affiliation: 1] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK. [2] Lao Oxford Mahosot Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.
authors.forename: David
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authors.affiliation: Lao Oxford Mahosot Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.
authors.forename: Viengmon
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authors.affiliation: 1] Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. [2] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Thwaites
authors.affiliation: 1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Paediatric Emergency Medicine, Chelsea and Westminster Hospital, London, UK.
authors.forename: Lalith
authors.initials: L
authors.lastname: Wijedoru
authors.affiliation: Centre for International Health and Otago International Health Research Network, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: John A
authors.identifier: 000000024529102X
authors.initials: JA
authors.lastname: Crump
authors.affiliation: Salmonella Reference Service, Public Health England, Colindale, London, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: De Pinna
authors.affiliation: Salmonella Reference Service, Public Health England, Colindale, London, UK.
authors.forename: Satheesh
authors.initials: S
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authors.affiliation: Emerging Disease Surveillance and Response, Division of Pacific Technical Support, World Health Organization, Suva, Fiji.
authors.forename: Eric J
authors.initials: EJ
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authors.affiliation: Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Duy Pham
authors.initials: DP
authors.lastname: Thanh
authors.affiliation: 1] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK. [2] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [3] Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Paul
authors.identifier: 0000000210137815
authors.initials: P
authors.lastname: Turner
authors.affiliation: Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
authors.forename: Sona
authors.initials: S
authors.lastname: Soeng
authors.affiliation: Microbiological Diagnostic Unit-Public Health Laboratory, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Valcanis
authors.affiliation: Microbiological Diagnostic Unit-Public Health Laboratory, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Joan
authors.initials: J
authors.lastname: Powling
authors.affiliation: Microbiological Diagnostic Unit-Public Health Laboratory, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Karolina
authors.initials: K
authors.lastname: Dimovski
authors.affiliation: Microbiological Diagnostic Unit-Public Health Laboratory, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Geoff
authors.initials: G
authors.lastname: Hogg
authors.affiliation: 1] Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. [2] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Kathryn E
authors.identifier: 0000000339492471
authors.initials: KE
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authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Gordon
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mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D058974:Phylogeography; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D012485:Salmonella typhi / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014435:Typhoid Fever / Q000188:drug therapy / Q000382:microbiology* / Q000635:transmission
chemical_list: D000900:Anti-Bacterial Agents; D011804:Quinolines; C037219:quinoline