Genomic investigations of S. Typhi isolated from Community and Hospital settings – An update from SEFI network

Abstract

Background: S. Typhi “H58/4.3.1”, a single dominant MDR-lineage has emerged and spread throughout Asia and Africa over the last 30 years. A large global study speculated South Asia might be the site of original emergence of 4.3.1. Through an ongoing national-wide network of Surveillance of Enteric Fever in India (SEFI), we aim to study the genomic signatures of S. Typhi across different settings. We undertook this study to determine the genotypes of S. Typhi isolated from community (Tier-1) and Hospital (Tier-3) settings in a Southern India region. Methods and materials: A total of 193 and 200 S. Typhi isolated from Tier 1 (Jan-2017 to Sep-2019) and Tier 3 (Nov-2017 to Sep-2019) as part of the network was included. Susceptibility testing was done for most common antimicrobials. At present, whole genome sequencing was done for 30 strains each from Tier-1 and 3. SNP and comparative genomic analysis of Tier 1 and 3 was done to infer difference in the genomic signatures. Geospatial mapping was generated for Tier 1 strains for cluster analysis to infer transmission-dynamic events. Results: Susceptibility rates to first-line agents were highest among community strains with no MDR, whereas 8 MDR strains were isolated from hospital cases. Ciprofloxacin resistance was seen in 5% (9/193) of community isolates compared to the high rates 32% (63/200) among hospital isolates. Notably, genomic analysis showed the dominance of a single H8-lineage 4.3.1.2 (30/30) in community isolates. However, hospital isolates had broader distribution such as 4.3.1.2 (18), 4.3.1.1 (7), 4.3.1.3 (1) and 2.2 and 3.3 respectively. Within the community collection, two sub groups with respect to QRDR profile with S83Y (SG-I) and S83F (SG-II) were found. Interestingly, all SG-II (17/30) appeared to be a single strain with no SNPs differences, being circulated in a defined community setting over 3 months. Conclusion: The baseline data generated here provides multiple insights in terms of a single clade 4.3.1.2 dominating in a community setting, while diverse genotypes seen among typhoid cases attending a tertiary care hospital. However, phylo-geographical analysis of all the isolates would provide a clear picture of the ongoing transmission dynamics between two settings.