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

doi:10.1038/ng.3281

. 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

Vanessa K Wong ¹, Stephen Baker ², Derek J Pickard ³, Julian Parkhill ³, Andrew J Page ³, Nicholas A Feasey ⁴, Robert A Kingsley ⁵, Nicholas R Thomson ⁶, Jacqueline A Keane ³, François-Xavier Weill ⁷, David J Edwards ⁸, Jane Hawkey ⁹, Simon R Harris ³, Alison E Mather ³, Amy K Cain ³, James Hadfield ³, Peter J Hart ¹⁰, Nga Tran Vu Thieu ¹¹, Elizabeth J Klemm ³, Dafni A Glinos ³, Robert F Breiman ¹², Conall H Watson ¹³, Samuel Kariuki ¹⁴, Melita A Gordon ¹⁵, Robert S Heyderman ¹⁶, Chinyere Okoro ³, Jan Jacobs ¹⁷, Octavie Lunguya ¹⁸, W John Edmunds ¹³, Chisomo Msefula ¹⁹, Jose A Chabalgoity ²⁰, Mike Kama ²¹, Kylie Jenkins ²², Shanta Dutta ²³, Florian Marks ²⁴, Josefina Campos ²⁵, Corinne Thompson ²⁶, Stephen Obaro ²⁷, Calman A MacLennan ²⁸, Christiane Dolecek ²⁹, Karen H Keddy ³⁰, Anthony M Smith ³⁰, Christopher M Parry ³¹, Abhilasha Karkey ³², E Kim Mulholland ³³, James I Campbell ²⁶, Sabina Dongol ³², Buddha Basnyat ³², Muriel Dufour ³⁴, Don Bandaranayake ³⁵, Take Toleafoa Naseri ³⁶, Shalini Pravin Singh ³⁷, Mochammad Hatta ³⁸, Paul Newton ³⁹, Robert S Onsare ⁴⁰, Lupeoletalalei Isaia ⁴¹, David Dance ³⁹, Viengmon Davong ⁴², Guy Thwaites ²⁶, Lalith Wijedoru ⁴³, John A Crump ⁴⁴, Elizabeth De Pinna ⁴⁵, Satheesh Nair ⁴⁵, Eric J Nilles ⁴⁶, Duy Pham Thanh ¹¹, Paul Turner ⁴⁷, Sona Soeng ⁴⁸, Mary Valcanis ⁴⁹, Joan Powling ⁴⁹, Karolina Dimovski ⁴⁹, Geoff Hogg ⁴⁹, Jeremy Farrar ²⁶, Kathryn E Holt ⁸, Gordon Dougan ³

Affiliations

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.

PMID: 25961941
PMCID: PMC4921243
DOI: 10.1038/ng.3281

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

Vanessa K Wong et al. Nat Genet. 2015 Jun.

. 2015 Jun;47(6):632-9.

doi: 10.1038/ng.3281. Epub 2015 May 11.

Authors

Vanessa K Wong ¹, Stephen Baker ², Derek J Pickard ³, Julian Parkhill ³, Andrew J Page ³, Nicholas A Feasey ⁴, Robert A Kingsley ⁵, Nicholas R Thomson ⁶, Jacqueline A Keane ³, François-Xavier Weill ⁷, David J Edwards ⁸, Jane Hawkey ⁹, Simon R Harris ³, Alison E Mather ³, Amy K Cain ³, James Hadfield ³, Peter J Hart ¹⁰, Nga Tran Vu Thieu ¹¹, Elizabeth J Klemm ³, Dafni A Glinos ³, Robert F Breiman ¹², Conall H Watson ¹³, Samuel Kariuki ¹⁴, Melita A Gordon ¹⁵, Robert S Heyderman ¹⁶, Chinyere Okoro ³, Jan Jacobs ¹⁷, Octavie Lunguya ¹⁸, W John Edmunds ¹³, Chisomo Msefula ¹⁹, Jose A Chabalgoity ²⁰, Mike Kama ²¹, Kylie Jenkins ²², Shanta Dutta ²³, Florian Marks ²⁴, Josefina Campos ²⁵, Corinne Thompson ²⁶, Stephen Obaro ²⁷, Calman A MacLennan ²⁸, Christiane Dolecek ²⁹, Karen H Keddy ³⁰, Anthony M Smith ³⁰, Christopher M Parry ³¹, Abhilasha Karkey ³², E Kim Mulholland ³³, James I Campbell ²⁶, Sabina Dongol ³², Buddha Basnyat ³², Muriel Dufour ³⁴, Don Bandaranayake ³⁵, Take Toleafoa Naseri ³⁶, Shalini Pravin Singh ³⁷, Mochammad Hatta ³⁸, Paul Newton ³⁹, Robert S Onsare ⁴⁰, Lupeoletalalei Isaia ⁴¹, David Dance ³⁹, Viengmon Davong ⁴², Guy Thwaites ²⁶, Lalith Wijedoru ⁴³, John A Crump ⁴⁴, Elizabeth De Pinna ⁴⁵, Satheesh Nair ⁴⁵, Eric J Nilles ⁴⁶, Duy Pham Thanh ¹¹, Paul Turner ⁴⁷, Sona Soeng ⁴⁸, Mary Valcanis ⁴⁹, Joan Powling ⁴⁹, Karolina Dimovski ⁴⁹, Geoff Hogg ⁴⁹, Jeremy Farrar ²⁶, Kathryn E Holt ⁸, Gordon Dougan ³

Affiliations

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.

PMID: 25961941
PMCID: PMC4921243
DOI: 10.1038/ng.3281

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.

PubMed Disclaimer

Conflict of interest statement

COMPETING FINANCIAL INTERESTS

The authors declare no competing financial interests.

Figures

Figure 1

Figure 1

Population structure of the 1,832 S. Typhi isolates analyzed in this study. (a) Temporal distribution of the S. Typhi isolates included in the study. (b) Rooted maximum-likelihood tree of S. Typhi inferred from 22,145 SNPs, rooted using an outgroup (S. enterica serovar Paratyphi A, isolate 9953_5_4_Outgroup_ParatyphiA_IndoA270_2010). The colored ring indicates the geographical origin of the isolates. Red arc, H58 lineage; labeled blue dashed lines, public reference genomes reported in Holt et al., including the CT18 (R) reference genome (AL513382); black dashed lines, other publicly available genomes. Branch lengths are indicative of the estimated substitution rate per variable site.

Figure 2

Figure 2

Population structure of the S. Typhi H58 lineage. Rooted maximum-likelihood phylogeny inferred from 1,534 SNPs identified in the 853 H58 isolates, rooted using an S. Typhi isolate from the nearest neighboring cluster of non-H58 isolates as an outgroup (black filled circle; isolate 10060_5_62_ Fij107364_2012). The colored ring indicates the countries of isolation; countries discussed in the text are labeled around the tree. Branch lengths are indicative of the estimated substitution rate per variable site.

Figure 3

Figure 3

Geographical persistence and routes for dissemination of S. Typhi H58. (a) Maximum-likelihood tree for the H58 lineage (I and II), with clades containing isolates from a single country collapsed into nodes (circles), sized to indicate the number of isolates in the clade and colored by country of isolation. Branches are colored to indicate the country of origin of descendant nodes. (b) Years of isolation for each phylogeographical cluster in the tree, indicated by lines spanning the earliest and latest years of isolation for each cluster and colored to indicate the country. Four regions with extensive local clonal expansion are highlighted by shaded boxes, spanning the phylogenetic (y axis) and temporal (x axis) extent of the expansion. Locations from which singleton isolates were clustered within the phylogeographical clusters are shown to the right, indicative of further onward transmission.

Figure 4

Figure 4

Major geographical transfers within the H58 lineage, inferred from the phylogenetic tree. The size of each arrow indicates the relative number of likely transfers between regions or countries.

Figure 5

Figure 5

Insertion site of the 24-kb composite transposon in CT18. A comparative analysis using genoPlotr of CT18 and H58 isolates ERL12960 (ERR343327) and 12148 (ERR343322) showed two integration sites of the transposon in the chromosome. The nucleotide sequence of the composite transposon was identical to that in the IncHI1-PST6 plasmid of H58 isolate 10425_1_48_Viety3-193_1997, which was sequenced for comparison. Tn, transposon; TSD, target site duplication.

Figure 6

Figure 6

Acquired multidrug resistance in the S. Typhi H58 lineage. Maximum-likelihood phylogeny from 1,534 SNPs of 853 H58 isolates rooted using an S. Typhi isolate from the nearest neighboring cluster of non-H58 isolates as an outgroup (isolate 10060_5_62_ Fij107364_2012) and surrounded by five colored rings representing (1) geographical origin in terms of region, (2) number of transposon-encoded resistance genes, (3) presence of resistance plasmids, (4) presence of IS1 insertion near the cyaA gene and (5) the site of chromosomal integration. Black radial dashed lines show the positions of public reference strains. Branch lengths are indicative of the estimated substitution rate per variable site.

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References

1. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002;347:1770–1782. - PubMed
1. Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. Lancet Infect Dis. 2005;5:623–628. - PubMed
1. Crump JA, Mintz ED. Global trends in typhoid and paratyphoid fever. Clin Infect Dis. 2010;50:241–246. - PMC - PubMed
1. Mogasale V, et al. Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment. Lancet Glob Health. 2014;2:e570–e580. - PubMed
1. Bodhidatta L, Taylor DN, Thisyakorn U, Echeverria P. Control of typhoid fever in Bangkok, Thailand, by annual immunization of schoolchildren with parenteral typhoid vaccine. Rev Infect Dis. 1987;9:841–845. - PubMed

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[1] Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002;347:1770–1782. - PubMed

[2] Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002;347:1770–1782. - PubMed

[3] Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. Lancet Infect Dis. 2005;5:623–628. - PubMed

[4] Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. Lancet Infect Dis. 2005;5:623–628. - PubMed

[5] Crump JA, Mintz ED. Global trends in typhoid and paratyphoid fever. Clin Infect Dis. 2010;50:241–246. - PMC - PubMed

[6] Crump JA, Mintz ED. Global trends in typhoid and paratyphoid fever. Clin Infect Dis. 2010;50:241–246. - PMC - PubMed

[7] Mogasale V, et al. Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment. Lancet Glob Health. 2014;2:e570–e580. - PubMed

[8] Mogasale V, et al. Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment. Lancet Glob Health. 2014;2:e570–e580. - PubMed

[9] Bodhidatta L, Taylor DN, Thisyakorn U, Echeverria P. Control of typhoid fever in Bangkok, Thailand, by annual immunization of schoolchildren with parenteral typhoid vaccine. Rev Infect Dis. 1987;9:841–845. - PubMed

[10] Bodhidatta L, Taylor DN, Thisyakorn U, Echeverria P. Control of typhoid fever in Bangkok, Thailand, by annual immunization of schoolchildren with parenteral typhoid vaccine. Rev Infect Dis. 1987;9:841–845. - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

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Grants and funding

LinkOut - more resources

Full Text Sources

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