The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi

The emergence of increasingly antimicrobial-resistant (AMR) Salmonella enterica serovar Typhi ( S . Typhi) threatens to undermine effective treatment and control. Here, aiming to investigate the temporal and geographic patterns of emergence and spread of AMR S . Typhi, we sequenced 3,489 S . Typhi isolated from prospective surveillance in South Asia and combined these with a global collection of 4,169 S . Typhi genomes. Our analysis revealed that independent acquisition of plasmids and homoplastic mutations conferring AMR have occurred repeatedly in multiple lineages of S . Typhi, predominantly arising in South Asia. We found evidence of frequent international and intercontinental transfers of AMR S . Typhi, followed by rapid expansion and replacement of antimicrobial-susceptible clades.