Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.
Wong VK., Baker S., Pickard DJ., Parkhill J., Page AJ., Feasey NA., Kingsley RA., Thomson NR., Keane JA., Weill F-X., Edwards DJ., Hawkey J., Harris SR., Mather AE., Cain AK., Hadfield J., Hart PJ., Thieu NTV., Klemm EJ., Glinos DA., Breiman RF., Watson CH., Kariuki S., Gordon MA., Heyderman RS., Okoro C., Jacobs J., Lunguya O., Edmunds WJ., Msefula C., Chabalgoity JA., Kama M., Jenkins K., Dutta S., Marks F., Campos J., Thompson C., Obaro S., MacLennan CA., Dolecek C., Keddy KH., Smith AM., Parry CM., Karkey A., Mulholland EK., Campbell JI., Dongol S., Basnyat B., Dufour M., Bandaranayake D., Naseri TT., Singh SP., Hatta M., Newton P., Onsare RS., Isaia L., Dance D., Davong V., Thwaites G., Wijedoru L., Crump JA., De Pinna E., Nair S., Nilles EJ., Thanh DP., Turner P., Soeng S., Valcanis M., Powling J., Dimovski K., Hogg G., Farrar J., Holt KE., Dougan G.
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.