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

Wong VK1, Baker S2, Pickard DJ3, Parkhill J3, Page AJ3, Feasey NA4, Kingsley RA5, Thomson NR6, Keane JA3, Weill FX7, Edwards DJ8, Hawkey J9, Harris SR3, Mather AE3, Cain AK3, Hadfield J3, Hart PJ10, Thieu NT11, Klemm EJ3, Glinos DA3, Breiman RF12, Watson CH13, Kariuki S14, Gordon MA15, Heyderman RS16, Okoro C3, Jacobs J17, Lunguya O18, Edmunds WJ13, Msefula C19, Chabalgoity JA20, Kama M21, Jenkins K22, Dutta S23, Marks F24, Campos J25,Thompson C26, Obaro S27, MacLennan CA28, Dolecek C29, Keddy KH30, Smith AM30, Parry CM31, Karkey A32, Mulholland EK33, Campbell JI26, Dongol S32,Basnyat B32, Dufour M34, Bandaranayake D35, Naseri TT36, Singh SP37, Hatta M38, Newton P39, Onsare RS40, Isaia L41, Dance D39, Davong V42, Thwaites G26, Wijedoru L43, Crump JA44, De Pinna E45, Nair S45, Nilles EJ46, Thanh DP11, Turner P47, Soeng S48, Valcanis M49, Powling J49, Dimovski K49, Hogg G49,Farrar J26, Holt KE8, Dougan G3.

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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.