A retrospective investigation of the population structure and geospatial distribution of Salmonella Paratyphi A in Kathmandu, Nepal

Salmonella Paratyphi A, one of the major etiologic agents of enteric fever, has been on the rise over the last decades in certain endemic regions compared to S. Typhi, the most prevalent cause of enteric fever. Despite this, data on the prevalence and molecular epidemiology of S. Paratyphi A remain scarce. Here, we analysed the whole genome sequences of a total of 216 S. Paratyphi A isolates originating in Nepal between 2005 and 2014, of which 200 were from acute patients and 16 from chronic carriers of enteric fever. By using the recently developed genotyping framework for S. Paratyphi A (paratype), we identified several genotypes circulating in Kathmandu. Importantly, we observed an unusual clonal expansion of genotype 2.4.3 over a four-year period that spread geographically and replaced other genotypes. This rapid genotype replacement is hypothesised to have been driven by both reduced sensitivity to fluoroquinolones and genetic changes to virulence factors, such as functional and structural genes of type 3 secretion systems. Finally, we show that person to person is likely the most common mode of transmission and chronic carriers play a limited role in maintaining disease circulation.