Genetic heterogeneity in the Salmonella Typhi Vi capsule locus: a population genomic study from Fiji

Typhoid fever is endemic in many parts of the world and remains a major public health concern in tropical and sub-tropical developing nations, including Fiji. To address high rates of typhoid fever, the Northern Division of Fiji implemented a mass vaccination with typhoid conjugate vaccine (Vi-polysaccharide conjugated to tetanus toxoid) as a public health control measure in 2023. In this study we define the genomic epidemiology of <i>Salmonella</i> Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (<i>n</i>=419) of the total cases from the Northern and Central Divisions of Fiji that occurred in the period 2017-2019. We found elevated rates of nucleotide polymorphisms in the <i>tviD</i> and <i>tviE</i> genes (responsible for Vi-polysaccharide synthesis) relative to core genome levels within the Fiji endemic <i>S</i>. Typhi genotype 4.2. Expansion of these findings within a globally representative database of 12 382 <i>S</i>. Typhi (86 genotyphi clusters) showed evidence of convergent evolution of the same <i>tviE</i> mutations across the <i>S</i>. Typhi population, indicating that <i>tvi</i> selection has occurred both independently and globally. The functional impact of <i>tvi</i> mutations on the Vi-capsular structure and other phenotypic characteristics are not fully elucidated, yet commonly occurring <i>tviE</i> polymorphisms localize adjacent to predicted active site residues when overlayed against the predicted TviE protein structure. Given the central role of the Vi-polysaccharide in <i>S</i>. Typhi biology and vaccination, further integrated epidemiological, genomic and phenotypic surveillance is required to determine the spread and functional implications of these mutations.