Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes

Megan E. Carey, Zoe A. Dyson, Danielle J. Ingle, Afreenish Amir, Mabel K. Aworh, Marie Anne Chattaway, Ka Lip Chew, John A. Crump, Nicholas A. Feasey, Benjamin P. Howden, Karen H. Keddy, Mailis Maes, Christopher M. Parry, Sandra Van Puyvelde, Hattie E. Webb, Ayorinde Oluwatobiloba Afolayan, Anna P. Alexander, Shalini Anandan, Jason R. Andrews, Philip M. AshtonBuddha Basnyat, Ashish Bavdekar, Isaac I. Bogoch, John D. Clemens, Kesia Esther da Silva, Anuradha De, Joep de Ligt, Paula Lucia Diaz Guevara, Christiane Dolecek, Shanta Dutta, Marthie M. Ehlers, Louise Francois Watkins, Denise O. Garrett, Gauri Godbole, Melita A. Gordon, Andrew R. Greenhill, Chelsey Griffin, Madhu Gupta, Rene S. Hendriksen, Robert S. Heyderman, Yogesh Hooda, Juan Carlos Hormazabal, Odion O. Ikhimiukor, Junaid Iqbal, Jobin John Jacob, Claire Jenkins, Dasaratha Ramaiah Jinka, Jacob John, Robert A. Kingsley, Gemma Langridge, Global Typhoid Genomics Consortium Group Authorship

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal ‘sentinel’ surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (=3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has becomedominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.

Original languageEnglish
Article numbere85867
JournaleLife
Volume12
DOIs
Publication statusPublished - 12 Sep 2023

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