Genomic epidemiology and emerging antimicrobial resistance profiles of Salmonella Paratyphi A in returning travellers to Australia

Enteric fever is endemic to many low- and middle-income countries (LMICs), particularly those in sub-Saharan Africa, South and South-East Asia. The causative agents are typhoidal serovars of Salmonella enterica, including Typhi (S. Typhi) and Paratyphi A (SPA). There are no vaccines currently licensed for SPA, leaving antimicrobials as the only therapeutic option. Multi-drug resistance (MDR) S. Typhi is increasingly prevalent, but to date has not been detected in SPA. In Australia, cases of SPA are notifiable. Here we report on the genomic epidemiology of 208 cases of SPA in returned travellers to Australia, and their close contacts, from 2018 to 2025. A total of 15 unique genotypes were detected, and these were correlated with geographical regions of reported travel. There was a low incidence of antimicrobial resistance with only a single isolate carrying acquired resistance genes. Mutations in quinolone resistance determining regions were common across the genotypes, detected in 95.7% of isolates. A single isolate in a traveller returning from India was resistant to several first line antibiotics including: ampicillin, amoxicillin plus clavulanic acid, ceftriaxone, azithromycin and ciprofloxacin. The isolate carried a plasmid encoding an extended spectrum beta-lactamase (blaCTX-M-231), two macrolide resistance genes (mphA and ermB) and a quinolone resistance gene (qnrS1). Elements of the pangenome were explored, with stable maintenance of small plasmids encoding hypothetical proteins detected in four genotypes. Copy number variation in genes encoding surface antigen biosynthesis genes were detected in six genotypes. These biosynthesis genes are targets for one of the two SPA vaccines in development, and the potential variation in surface antigens could have implications for vaccine efficacy. Linking epidemiological data with genomic studies of SPA provides an opportunity to improve understanding of the emergence, spread and risk of drug-resistant SPA infections, and to better inform empirical treatment guidelines in returned travellers.