Abstract
BackgroundTyphoid fever caused by Salmonella Typhi is a major public health concern in low-/middle-income countries. A recent study of 1900 global S. Typhi indicated that South Asia might be the site of the original emergence of the most successful and hypervirulent clone belonging to the 4.3.1 genotype. However, this study had limited samples from India.MethodsWe analyzed 194 clinical S. Typhi, temporal representatives from those isolated from blood and bone marrow cultures in southern India, over 26 years (1991–2016). Antimicrobial resistance (AMR) testing was performed for most common clinical agents. Whole-genome sequencing and SNP-level analysis was conducted. Comparative genomics of Vellore isolates was performed to infer transmission and AMR events.ResultsWe identified multidrug-resistance (MDR)–associated clade 4.3.1 as the dominant genotype. We detected 4.3.1 S. Typhi as early as 1991, the earliest to be reported form India, and the majority were fluoroquinolone resistant and not MDR. MDR was not detected at all in other genotypes circulating in Vellore. Comparison with global S. Typhi showed 2 Vellore subgroups (I and II) that were phylogenetically highly related to previously described South Asia (subgroup I, II) and Southeast Asia (subgroup II) clades.Conclusions4.3.1 S. Typhi has dominated in Vellore for 2 decades. Our study would assist public health agencies in better tracking of transmission and persistence of this successful clade in India and globally. It informs clinicians of the AMR pattern of circulating clone, which would add confidence to their prophylactic/treatment decision making and facilitate efficient patient care.
Highlights
MethodsTemporal representatives from those isolated from blood and bone marrow cultures in southern India, over 26 years (1991–2016)
Typhoid fever caused by Salmonella Typhi is a major public health concern in low-/middle-income countries
Typhoid fever is a systemic infection caused by the gram-negative enteric bacteria Salmonella enterica serovar Typhi
Summary
Temporal representatives from those isolated from blood and bone marrow cultures in southern India, over 26 years (1991–2016). Salmonella Typhi isolates were from blood and bone marrow cultures obtained from individuals attending the Christian Medical College Hospital, Vellore, between 1991 and 2016. Typhi were retrieved from the archived stocks (4462 isolates) and selected for detailed genomic analysis. These 194 isolates were chosen as being representative of temporal distribution of this study period. The study isolates were assigned to the previously described lineages based on the single nucleotide polymorphisms (SNPs) using an extended genotypic framework and genotyped as 4.3.1 and/or other genotypes [20]. For the 4.3.1 lineage subtrees, CT18 was used as an outgroup and root
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