The molecular epidemiology of Salmonella Typhi and applications for policy
type: CreativeWork
description: Salmonella Typhi (S. Typhi) is a Gram-negative bacterium and the etiologic agent of typhoid fever. High rates of typhoid were historically associated with urban slums in South Asia with poor sanitation, but recent multicentre surveillance studies have demonstrated that typhoid is also a major problem of urban and rural areas in sub-Saharan Africa. Typhoid necessitates antimicrobial therapy; however, antimicrobial resistance (AMR) poses a serious threat to the effective clinical management of typhoid, particularly in South Asia, where resistance to all oral antimicrobials used to treat typhoid has been reported. New typhoid conjugate vaccines (TCVs) are highly efficacious and two have been prequalified by the World Health Organization (WHO); a small number of countries have introduced TCVs into their national immunization programs. However, many countries lack primary surveillance data to inform decision-making for TCV introduction. Here, aiming to aggregate and analyse globally representative whole genome sequencing (WGS) data to inform public health action, I conducted a genomic investigation of the global distribution and transmission dynamics of AMR S. Typhi. With colleagues from Pakistan and India, I conducted phylogenetic analyses of the first molecularly confirmed azithromycin-resistant S. Typhi isolated in Pakistan and India and put them into context with contemporaneous azithromycin-resistant isolates. I found that single point mutations in acrB (efflux pump) were emerging independently in these settings, potentially associated with selective pressure. AMR in S. Typhi is associated with the H58 lineage, which arose recently before becoming globally dominant within a relatively short time. Given this lineage’s association with AMR, I sought to investigate how, when, and where it emerged. Working with collaborators from the United Kingdom Health Security Agency (UKHSA), we performed phylogenetic and phylodynamic analyses using S. Typhi from returning traveller…
abstract: Salmonella Typhi (S. Typhi) is a Gram-negative bacterium and the etiologic agent of typhoid fever. High rates of typhoid were historically associated with urban slums in South Asia with poor sanitation, but recent multicentre surveillance studies have demonstrated that typhoid is also a major problem of urban and rural areas in sub-Saharan Africa. Typhoid necessitates antimicrobial therapy; however, antimicrobial resistance (AMR) poses a serious threat to the effective clinical management of typhoid, particularly in South Asia, where resistance to all oral antimicrobials used to treat typhoid has been reported. New typhoid conjugate vaccines (TCVs) are highly efficacious and two have been prequalified by the World Health Organization (WHO); a small number of countries have introduced TCVs into their national immunization programs. However, many countries lack primary surveillance data to inform decision-making for TCV introduction. Here, aiming to aggregate and analyse globally representative whole genome sequencing (WGS) data to inform public health action, I conducted a genomic investigation of the global distribution and transmission dynamics of AMR S. Typhi. With colleagues from Pakistan and India, I conducted phylogenetic analyses of the first molecularly confirmed azithromycin-resistant S. Typhi isolated in Pakistan and India and put them into context with contemporaneous azithromycin-resistant isolates. I found that single point mutations in acrB (efflux pump) were emerging independently in these settings, potentially associated with selective pressure. AMR in S. Typhi is associated with the H58 lineage, which arose recently before becoming globally dominant within a relatively short time. Given this lineage’s association with AMR, I sought to investigate how, when, and where it emerged. Working with collaborators from the United Kingdom Health Security Agency (UKHSA), we performed phylogenetic and phylodynamic analyses using S. Typhi from returning traveller…
author: Carey, Megan
language: eng
keywords: Antmicrobial resistance, Salmonella Typhi, Typhoid conjugate vaccine, Antimicrobial stewardship, Vaccine introduction, Typhoid genomics
license: https://www.repository.cam.ac.uk/bitstreams/e7c38c98-7010-4f38-8d4e-44f194363fc6/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2022-10-04
date modified: 2026-07-22T22:23:56Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.96597