1887

Abstract

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 Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (=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 and genes (responsible for Vi-polysaccharide synthesis) relative to core genome levels within the Fiji endemic . Typhi genotype 4.2. Expansion of these findings within a globally representative database of 12 382 . Typhi (86 genotyphi clusters) showed evidence of convergent evolution of the same mutations across the . Typhi population, indicating that selection has occurred both independently and globally. The functional impact of mutations on the Vi-capsular structure and other phenotypic characteristics are not fully elucidated, yet commonly occurring 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 . Typhi biology and vaccination, further integrated epidemiological, genomic and phenotypic surveillance is required to determine the spread and functional implications of these mutations.

Funding
This study was supported by the:
  • Department of Health, State Government of Victoria
  • Bill and Melinda Gates Foundation (Award OPP1017518)
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-09-10
2024-10-15
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