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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.

Funding

No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

SUBMITTER: Carey ME 

PROVIDER: S-EPMC10506625 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Carey Megan E ME   Dyson Zoe A ZA   Ingle Danielle J DJ   Amir Afreenish A   Aworh Mabel K MK   Chattaway Marie Anne MA   Chew Ka Lip KL   Crump John A JA   Feasey Nicholas A NA   Howden Benjamin P BP   Keddy Karen H KH   Maes Mailis M   Parry Christopher M CM   Van Puyvelde Sandra S   Webb Hattie E HE   Afolayan Ayorinde Oluwatobiloba AO   Alexander Anna P AP   Anandan Shalini S   Andrews Jason R JR   Ashton Philip M PM   Basnyat Buddha B   Bavdekar Ashish A   Bogoch Isaac I II   Clemens John D JD   da Silva Kesia Esther KE   De Anuradha A   de Ligt Joep J   Diaz Guevara Paula Lucia PL   Dolecek Christiane C   Dutta Shanta S   Ehlers Marthie M MM   Francois Watkins Louise L   Garrett Denise O DO   Godbole Gauri G   Gordon Melita A MA   Greenhill Andrew R AR   Griffin Chelsey C   Gupta Madhu M   Hendriksen Rene S RS   Heyderman Robert S RS   Hooda Yogesh Y   Hormazabal Juan Carlos JC   Ikhimiukor Odion O OO   Iqbal Junaid J   Jacob Jobin John JJ   Jenkins Claire C   Jinka Dasaratha Ramaiah DR   John Jacob J   Kang Gagandeep G   Kanteh Abdoulie A   Kapil Arti A   Karkey Abhilasha A   Kariuki Samuel S   Kingsley Robert A RA   Koshy Roshine Mary RM   Lauer A C AC   Levine Myron M MM   Lingegowda Ravikumar Kadahalli RK   Luby Stephen P SP   Mackenzie Grant Austin GA   Mashe Tapfumanei T   Msefula Chisomo C   Mutreja Ankur A   Nagaraj Geetha G   Nagaraj Savitha S   Nair Satheesh S   Naseri Take K TK   Nimarota-Brown Susana S   Njamkepo Elisabeth E   Okeke Iruka N IN   Perumal Sulochana Putli Bai SPB   Pollard Andrew J AJ   Pragasam Agila Kumari AK   Qadri Firdausi F   Qamar Farah N FN   Rahman Sadia Isfat Ara SIA   Rambocus Savitra Devi SD   Rasko David A DA   Ray Pallab P   Robins-Browne Roy R   Rongsen-Chandola Temsunaro T   Rutanga Jean Pierre JP   Saha Samir K SK   Saha Senjuti S   Saigal Karnika K   Sajib Mohammad Saiful Islam MSI   Seidman Jessica C JC   Shakya Jivan J   Shamanna Varun V   Shastri Jayanthi J   Shrestha Rajeev R   Sia Sonia S   Sikorski Michael J MJ   Singh Ashita A   Smith Anthony M AM   Tagg Kaitlin A KA   Tamrakar Dipesh D   Tanmoy Arif Mohammed AM   Thomas Maria M   Thomas Mathew S MS   Thomsen Robert R   Thomson Nicholas R NR   Tupua Siaosi S   Vaidya Krista K   Valcanis Mary M   Veeraraghavan Balaji B   Weill François-Xavier FX   Wright Jackie J   Dougan Gordon G   Argimón Silvia S   Keane Jacqueline A JA   Aanensen David M DM   Baker Stephen S   Holt Kathryn E KE  

eLife 20230912


<h4>Background</h4>The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse <i>Salmonella enterica</i> 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).<h4>Methods</h4>This is a meta-analysis of global genotype and antimicrobial resistance (AMR) dete  ...[more]

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