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In 2013, an unusual increase in the number of Salmonella enterica serotype Paratyphi A (Salmonella Paratyphi A) infections was reported in patients in Phnom Penh, Cambodia, and in European, American and Japanese travellers returning from Cambodia. Epidemiological investigations failed to identify a common source of exposure. Whole-genome sequencing was performed on 65 Salmonella Paratyphi A isolates: 48 from infections acquired in Cambodia between 1999 and 2014 (in both local residents and travellers) and 17 from infections acquired in other countries in Asia, Africa and Europe between 2002 and 2014. Short-read sequences from 80 published Salmonella Paratyphi A genomes from around the world and from 13 published Salmonella Paratyphi genomes associated with an outbreak in China were included in the study. Pulsed-field gel electrophoresis was performed on a subset of the isolates. All but four of the 47 isolates acquired in Cambodia between 2010 and 2014 belonged to the same clade, C5, of lineage C. This clade has been isolated in Cambodia since at least 1999. The Cambodian outbreak clade isolates displayed pan-susceptibility to antibiotics. Only one C5 isolate, collected in 2000, was resistant to quinolone and was found to carry a gyrA mutation (Ser83Phe). The Cambodian outbreak strain was different from that responsible for an outbreak in China in 2010–2011 (clade C4). Pan-genome analysis revealed no gains of particular accessory genes or losses of common genes in the C5 clade that might account for a possible selective advantage. Environmental and/or human behavioural factors are, therefore, likely to explain the recent increase in the incidence of Salmonella Paratyphi A infections in Cambodia. |