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Authors: Wong, Vanessa K and Baker, Stephen and Pickard, Derek J and Parkhill, Julian and Page, Andrew J and Feasey, Nicholas A and Kingsley, Robert A and Thomson, Nicholas R and Keane, Jacqueline A and Weill, François-Xavier and Edwards, David J and Hawkey, Jane and Harris, Simon R and Mather, Alison E and Cain, Amy K and Hadfield, James and Hart, Peter J and Thieu, Nga Tran Vu and Klemm, Elizabeth J and Glinos, Dafni A and Breiman, Robert F and Watson, Conall H and Kariuki, Samuel and Gordon, Melita A and Heyderman, Robert S and Okoro, Chinyere and Jacobs, Jan and Lunguya, Octavie and Edmunds, W John and Msefula, Chisomo and Chabalgoity, Jose A and Kama, Mike and Jenkins, Kylie and Dutta, Shanta and Marks, Florian and Campos, Josefina and Thompson, Corinne and Obaro, Stephen and MacLennan, Calman A and Dolecek, Christiane and Keddy, Karen H and Smith, Anthony M and Parry, Christopher M and Karkey, Abhilasha and Mulholland, E Kim and Campbell, James I and Dongol, Sabina and Basnyat, Buddha and Dufour, Muriel and Bandaranayake, Don and Naseri, Take Toleafoa and Singh, Shalini Pravin and Hatta, Mochammad and Newton, Paul and Onsare, Robert S and Isaia, Lupeoletalalei and Dance, David and Davong, Viengmon and Thwaites, Guy and Wijedoru, Lalith and Crump, John A and De Pinna, Elizabeth and Nair, Satheesh and Nilles, Eric J and Thanh, Duy Pham and Turner, Paul and Soeng, Sona and Valcanis, Mary and Powling, Joan and Dimovski, Karolina and Hogg, Geoff and Farrar, Jeremy and Holt, Kathryn E and Dougan, Gordon

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.

Journal: Nature genetics
DOI: 10.1038/ng.3281
Year: 2015

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