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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by a Wellcome senior research fellowship to SB (215515/Z/19/Z). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Samples were obtained from studies that were approved by the institutional ethical review boards of Patan Hospital, The Nepal Health Research Council, and The Oxford University Tropical Research Ethics Committee. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All supporting data, code, methods, and accession numbers have been provided within the article or through supplementary data files. Two supplementary tables with all accession numbers are available.