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

Abstract

AbstractSalmonellaParatyphi A, one of the major etiologic agents of enteric fever, has been on the rise over the last decades in certain endemic regions compared toS.Typhi, the most prevalent cause of enteric fever. Despite this, data on the prevalence and molecular epidemiology ofS.Paratyphi A remain scarce. Here, we analysed the whole genome sequences of a total of 216S. 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 forS. 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.