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Nat Genet. 2015 Jun;47(6):632-9. doi: 10.1038/ng.3281. Epub 2015 May 11.

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

Author information

1
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.
2
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.
3
Wellcome Trust Sanger Institute, Hinxton, UK.
4
Liverpool School of Tropical Medicine, Liverpool, UK.
5
1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Institute of Food Research, Norwich Research Park, Norwich, UK.
6
1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
7
Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Paris, France.
8
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia.
9
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.
10
Institute of Biomedical Research, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK.
11
Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
12
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.
13
Centre for the Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
14
1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
15
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
16
Malawi-Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.
17
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.
18
1] National Institute for Biomedical Research, Kinshasa, Democratic Republic of the Congo. [2] University Hospital of Kinshasa, Kinshasa, Democratic Republic of the Congo.
19
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.
20
Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Montevideo, Uruguay.
21
Ministry of Health, Suva, Fiji.
22
Fiji Health Sector Support Program, Suva, Fiji.
23
National Institute of Cholera and Enteric Diseases, Kolkata, India.
24
International Vaccine Institute, Department of Epidemiology, Seoul, Republic of Korea.
25
Enteropathogen Division, Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) Carlos G. Malbran Institute, Buenos Aires, Argentina.
26
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.
27
1] Division of Pediatric Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA. [2] University of Abuja Teaching Hospital, Abuja, Nigeria. [3] Bingham University, Karu, Nigeria.
28
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.
29
Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
30
Centre for Enteric Diseases, National Institute for Communicable Diseases, Division in the National Health Laboratory Service, University of the Witwatersrand, Johannesburg, South Africa.
31
1] Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK. [2] Graduate School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
32
Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
33
1] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. [2] Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
34
Enteric and Leptospira Reference Laboratory, Institute of Environmental Science and Research, Ltd. (ESR), Porirua, New Zealand.
35
National Centre for Biosecurity and Infectious Disease, Institute of Environmental Science and Research, Porirua, New Zealand.
36
Samoa Ministry of Health, Apia, Samoa.
37
National Influenza Center, World Health Organization, Center for Communicable Disease Control, Suva, Fiji.
38
Department of Microbiology, Hasanuddin University, Makassar, Indonesia.
39
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.
40
Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
41
National Health Services, Tupua Tamasese Meaole Hospital, Apia, Samoa.
42
Lao Oxford Mahosot Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.
43
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.
44
Centre for International Health and Otago International Health Research Network, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
45
Salmonella Reference Service, Public Health England, Colindale, London, UK.
46
Emerging Disease Surveillance and Response, Division of Pacific Technical Support, World Health Organization, Suva, Fiji.
47
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.
48
Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
49
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.

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.

PMID:
25961941
PMCID:
PMC4921243
DOI:
10.1038/ng.3281
[Indexed for MEDLINE]
Free PMC Article

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