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

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 become dominant 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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.7554/elife.85867

Authors

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Role:
Author
ORCID:
0000-0002-7797-9080
More by this author
Role:
Author
ORCID:
0000-0002-8887-3492
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Role:
Author
ORCID:
0000-0003-4213-6929

Contributors

Division:
MSD
Department:
NDM
Sub department:
Big Data Institute
Role:
Contributor


Publisher:
eLife Sciences Publications
Journal:
eLife More from this journal
Volume:
12
Article number:
e85867
Place of publication:
England
Publication date:
2023-09-12
Acceptance date:
2023-08-02
DOI:
EISSN:
2050-084X
Pmid:
37697804


Language:
English
Pubs id:
1525737
Local pid:
pubs:1525737
Deposit date:
2023-10-09
ARK identifier:

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