Exploring the genomic background of Salmonella enterica serovar Paratyphi A from Bangladesh using Next Generation Sequencing

Salmonella enterica serovar Paratyphi A, the etiologic agent of paratyphoid fever, can lead to severe illness if treatment is delayed or inappropriate. Each year, this acute infectious disease affects more than three million people globally, causing ~19,000 deaths. With some geographic exceptions (e.g. China, Myanmar), Salmonella Paratyphi A has always been less prevalent than Salmonella enterica serovar Typhi. Also, due to the striking similarity with Salmonella Typhi regarding host selection and clinical characteristics, this lesser-known pathogen is often neglected. Moreover, the current intervention, treatment, and investment strategies for paratyphoid fever have been imposed utilizing the data available on Salmonella Typhi. Consequently, low and middle-income countries such as Bangladesh, India, Nepal, and Pakistan lack enough data to determine the epidemiology, antimicrobial resistance (AMR), and population structure specific to Salmonella Paratyphi A. In January 2018, WHO prequalified a typhoid conjugate vaccine, Typbar-TCV for the routine immunization of children in typhoid endemic regions. This conjugate vaccine seems to provide long-lasting immunity against Salmonella Typhi and has proven to be highly efficacious in a recent phase 3 trial in Nepal. Unfortunately, in the case of Salmonella Paratyphi A, there has been no evidence of such protection given by Typbar-TCV and after introduction, there is a possibility that this single-dose conjugate vaccine will leave paratyphoid cases untouched. At this moment, the global incidence of paratyphoid is less compared to typhoid, but with the recent reports of growing numbers in several Asian countries combined with a strong probability of a reduction in Salmonella Typhi, this lesser-known pathogen may emerge as a new threat in the coming days. To tackle some of these challenges, we recently conducted a 18-year retrospective study on antimicrobial resistance patterns of Salmonella Paratyphi A isolated in Bangladesh. This study generated the largest isolate collection of this organism (N= ~640) and we randomly selected 348 from there for whole-genome sequencing. Our genomic analysis showed that antimicrobial resistance patterns of this neglected pathogen are different from Salmonella Typhi, highlighting the need for revised antibiotic therapy/stewardship guidelines for Salmonella Paratyphi A. Moreover, with rising antimicrobial resistance, and no licensed vaccines, genomic surveillance is of utmost importance to track the evolution of this pathogen and monitor transmission. To help with such studies, we developed Paratype, an open-access genotyping tool that segregates Salmonella Paratyphi A population into three primary and nine secondary clades, and 18 genotypes. Each genotype has been assigned a unique allele definition located on a conserved, essential gene. Using Paratype, we identified genomic variation between different sampling locations and specific antimicrobial resistance markers present in Salmonella Paratyphi A. This tool will assist future genomic surveillance studies tracking Salmonella Paratyphi A across the globe.