A genomic snapshot of Salmonella enterica serovar Typhi in Colombia.

Little is known about the genetic diversity of Salmonella enterica serovar Typhi (S. Typhi) circulating in Latin America. It has been observed that typhoid fever is still endemic in this part of the world; however, a lack of standardized blood culture surveillance across Latin American makes estimating the true disease burden problematic. The Colombian National Health Service established a surveillance system for tracking bacterial pathogens, including S. Typhi, in 2006. Here, we characterized 77 representative Colombian S. Typhi isolates collected between 1997 and 2018 using pulse field gel electrophoresis (PFGE; the accepted genotyping method in Latin America) and whole genome sequencing (WGS). We found that the main S. Typhi clades circulating in Colombia were clades 2.5 and 3.5. Notably, the sequenced S. Typhi isolates from Colombia were closely related in a global phylogeny. Consequently, these data suggest that these are endemic clades circulating in Colombia. We found that AMR in S. Typhi in Colombia was uncommon, with a small subset of organisms exhibiting mutations associated with reduced susceptibility to fluoroquinolones. This is the first time that S. Typhi isolated from Colombia have been characterized by WGS, and after comparing these data with those generated using PFGE, we conclude that PFGE is unsuitable for tracking S. Typhi clones and mapping transmission. The genetic diversity of pathogens such as S. Typhi is limited in Latin America and should be targeted for future surveillance studies incorporating WGS. Author summary: Salmonella Typhi is the causative agent of typhoid fever, with between 9–13 million cases and 116,800 associated deaths annually. Typhoid fever is still a public health problem mainly in low and middle-income countries (LMICs), including in Latin America, which has a modelled incidence of up to 169 (32–642) cases per 100,000 person-years. Several international studies have aimed to fill data gaps regarding the global distribution and genetic landscape of typhoid; however, in spite of these efforts Latin America is still underrepresented. The globally dominant lineages of S. Typhi (e.g., H58), which often carry multi-drug resistance (MDR) plasmids, decreased fluoroquinolone susceptibility, and now azithromycin resistance, are not detectable by the accepted method (PFGE) used to track outbreaks of typhoid in Latin America. We compared PFGE with whole genome sequence (WGS) and found it correlated poorly, resulting in the over clustering of cases. We additionally found that unlike in most endemic countries, S. Typhi in Colombia are highly antimicrobial susceptible and restricted to a limited number of genotypes that are not as commonly identified in other S. Typhi endemic countries. Our study provides the first enhanced insights into the molecular epidemiology of S. Typhi in Colombia, using WGS data for the first time to investigate the population structure in Colombia and identifying predominant circulating genotypes. Our work demonstrates that routine surveillance with the integration of WGS is necessary not only to improve disease burden estimates, but also to track the national and regional transmission dynamics of S. Typhi. [ABSTRACT FROM AUTHOR]