Browse by author
Lookup NU author(s): Dr Matt BawnORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: The continued emergence of Salmonella enterica serovar Typhi, with ever increasing antimicrobial resistance, necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe, in 2018 from a multidrug resistant S Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine programme. We aimed to investigate the emergence and evolution of antimicrobial resistance of endemic S Typhi in Zimbabwe and to determine the population structure, gene flux, and sequence polymorphisms of strains isolated before a typhoid conjugate vaccine programme to provide a baseline for future evaluation of the effect of the vaccination programme. Methods: In this genomic epidemiology study, we used short-read whole-genome sequencing of S Typhi isolated from clinical cases of typhoid fever in Harare, Zimbabwe, between Jan 1, 2012, and Feb 9, 2019, to determine the S Typhi population structure, gene flux, and sequence polymorphisms and reconstructed the evolution of antimicrobial resistance. Maximum likelihood time-scaled phylogenetic trees of Zimbabwe isolates in the context of global isolates obtained from the National Center for Biotechnology Information were constructed to infer spread and emergence of antimicrobial resistance. Findings: The population structure of S Typhi in Harare, Zimbabwe, from 2012 to 2019 was dominated by multidrug resistant genotype 4.3.1.1.EA1 (H58) that spread to Zimbabwe from neighbouring countries in around 2009 (95% credible interval 2008·5–2010·0). Acquisition of an IncN plasmid carrying antimicrobial resistance genes including a qnrS gene and a mutation in the quinolone resistance determining region of gyrA gene contributed to non-susceptibility and resistance to quinolone antibiotics. A minority population of antimicrobial susceptible S Typhi genotype 3.3.1 strains were present throughout. Interpretation: The currently dominant S Typhi population is genotype 4.3.1.1 that spread to Zimbabwe and acquired additional antimicrobial resistance though acquisition of a plasmid and mutation in the gyrA gene. This study provides a baseline population structure for future evaluation of the effect of the typhoid conjugate vaccine programme in Harare. Funding: Bill & Melinda Gates Foundation and the Biotechnology and Biological Sciences Research Council Institute Strategic Programme.
Author(s): Thilliez G, Mashe T, Chaibva BV, Robertson V, Bawn M, Tarupiwa A, Takawira FT, Kock MM, Midzi S, Mwamakamba LW, Matheu J, Juru A, Kingsley RA, Ehlers MM
Publication type: Article
Publication status: Published
Journal: The Lancet Microbe
Year: 2023
Volume: 4
Issue: 12
Pages: e1005-e1014
Print publication date: 01/12/2023
Online publication date: 09/11/2023
Acceptance date: 02/04/2018
Date deposited: 10/02/2025
ISSN (electronic): 2666-5247
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/ S2666-5247(23)00214-8
DOI: 10.1016/S2666-5247(23)00214-8
Data Access Statement: All sequence data are freely available from the Short Read Archive of the National Center for Biotechnology Information under accession numbers listed in the appendix (pp 12–63). Sample metadata are summarised in the appendix (pp 12–63)
Altmetrics provided by Altmetric
