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 language | English |
---|---|
Article number | e85867 |
Journal | eLife |
Volume | 12 |
DOIs | |
Publication status | Published - 12 Sep 2023 |
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Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes. / Carey, Megan E.; Dyson, Zoe A.; Ingle, Danielle J. et al.
In: eLife, Vol. 12, e85867, 12.09.2023.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
AU - Carey, Megan E.
AU - Dyson, Zoe A.
AU - Ingle, Danielle J.
AU - Amir, Afreenish
AU - Aworh, Mabel K.
AU - Chattaway, Marie Anne
AU - Chew, Ka Lip
AU - Crump, John A.
AU - Feasey, Nicholas A.
AU - Howden, Benjamin P.
AU - Keddy, Karen H.
AU - Maes, Mailis
AU - Parry, Christopher M.
AU - Van Puyvelde, Sandra
AU - Webb, Hattie E.
AU - Afolayan, Ayorinde Oluwatobiloba
AU - Alexander, Anna P.
AU - Anandan, Shalini
AU - Andrews, Jason R.
AU - Ashton, Philip M.
AU - Basnyat, Buddha
AU - Bavdekar, Ashish
AU - Bogoch, Isaac I.
AU - Clemens, John D.
AU - da Silva, Kesia Esther
AU - De, Anuradha
AU - Ligt, Joep de
AU - Guevara, Paula Lucia Diaz
AU - Dolecek, Christiane
AU - Dutta, Shanta
AU - Ehlers, Marthie M.
AU - Watkins, Louise Francois
AU - Garrett, Denise O.
AU - Godbole, Gauri
AU - Gordon, Melita A.
AU - Greenhill, Andrew R.
AU - Griffin, Chelsey
AU - Gupta, Madhu
AU - Hendriksen, Rene S.
AU - Heyderman, Robert S.
AU - Hooda, Yogesh
AU - Hormazabal, Juan Carlos
AU - Ikhimiukor, Odion O.
AU - Iqbal, Junaid
AU - Jacob, Jobin John
AU - Jenkins, Claire
AU - Jinka, Dasaratha Ramaiah
AU - John, Jacob
AU - Kingsley, Robert A.
AU - Langridge, Gemma
AU - Global Typhoid Genomics Consortium Group Authorship
N1 - Data availability All data analysed during this study are publicly accessible. Raw Illumina sequence reads have been submitted to the European Nucleotide Archive (ENA), and individual sequence accession numbers are listed in Supplementary file 2. The full set of n=13,000 genome assemblies generated for this study are available for download from FigShare: https://doi.org/10.26180/21431883. All assemblies of suitable quality (n=12,849) are included as public data in the online platform Pathogenwatch (https://pathogen.watch). The data are organised into collections, which each comprise a neighbour-joining phylogeny annotated with metadata, genotype, AMR determinants, and a linked map. Each contributing study has its own collection, browsable at https://pathogen.watch/collections/all?organismId=90370. In addition, we have provided three large collections, each representing roughly a third of the total dataset presented in this study: Typhi 4.3.1.1 (https://pathogen.watch/collection/2b7mp173dd57-clade-4311), Typhi lineage 4 (excluding 4.3.1.1) (https://pathogen.watch/collection/wgn6bp1c8bh6-clade-4-excluding-4311), and Typhi lineages 0-3 (https://pathogen.watch/collection/9o4bpn0418n3-clades-0-1-2-and-3). In addition, users can browse the full set of Typhi genomes in Pathogenwatch and select subsets of interest (e.g. by country, genotype, and/or resistance) to generate a collection including neighbour-joining tree for interactive exploration. Funding information: HORIZON EUROPE Marie Sklodowska-Curie Actions (845681); Bill and Melinda Gates Foundation (OPP1217121, OPP1194582, OPP1113007, INV-042340, OPPGH5231, OPP1020327, INV-036234, OPP1558210, OPP1151153, INV-008335, INV-029806, OPP1161058, OPP1141321, INV-108979, OPP1175797); Biotechnology and Biological Sciences Research Council (BB/R012504/1 and BBS/E/F/00PR10348); Wellcome Trust (Senior Fellowship); National Institutes of Health (F30AI156973, U01AI062563, 16_136_111, R01AI099525) Wellcome Trust (206194); Canadian Institutes of Health Research; National Institute for Health Research (Global Health Unit on Genomic Surveillance of AMR); Department of Health and Social Care (Fleming Fund); UK Medical Research Council (MR/L00464X/1, (Joint Global Health Trials Scheme MR/TOO5033/1); Institut Pasteur and Santé Publique France; United States Department of Health and Human Services (U19AI110820); Indian Council of Medical Research; World Health Organization and Gavi, the Vaccine Alliance; National Institute for Health and Care Research (NIHR Professor of Global Health); Department for Health and Social Care, the Department for International Development/Global Challenges Research Fund, the UK Medical Research Council, and the Wellcome Trust; National Institute for Health Research (National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Genomics and Enabling Data at University of Warwick in partnership with the UK Health Security Agency (UKHSA)); National Institutes of Health (R01TW009237); National Institutes of Health (R01AI121378); Wellcome (206545/7/17/Z and 106158/7/14/Z); National Institute for Health Research (Professorship NIHR300039, NIHR300039). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Rights Retention Statement: For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.
PY - 2023/9/12
Y1 - 2023/9/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85175204073&partnerID=8YFLogxK
U2 - 10.7554/ELIFE.85867
DO - 10.7554/ELIFE.85867
M3 - Article
AN - SCOPUS:85175204073
VL - 12
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e85867
ER -