Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Authors: Carey Megan E , Dyson Zoe A , Ingle Danielle J , Amir Afreenish , Aworh Mabel K , Chattaway Marie Anne , Chew Ka Lip , Crump John A , Feasey Nicholas A , Howden Benjamin P , Keddy Karen H , Maes Mailis , Parry Christopher M , Van Puyvelde Sandra , Webb Hattie E , Afolayan Ayorinde Oluwatobiloba , Alexander Anna P , Anandan Shalini , Andrews Jason R , Ashton Philip M , Basnyat Buddha , Bavdekar Ashish , Bogoch Isaac I , Clemens John D , da Silva Kesia Esther , De Anuradha , de Ligt Joep , Diaz Guevara Paula Lucia , Dolecek Christiane , Dutta Shanta , Ehlers Marthie M , Francois Watkins Louise , Garrett Denise O , Godbole Gauri , Gordon Melita A , Greenhill Andrew R , Griffin Chelsey , Gupta Madhu , Hendriksen Rene S , Heyderman Robert S , Hooda Yogesh , Hormazabal Juan Carlos , Ikhimiukor Odion O , Iqbal Junaid , Jacob Jobin John , Jenkins Claire , Jinka Dasaratha Ramaiah , John Jacob , Kang Gagandeep , Kanteh Abdoulie , Kapil Arti , Karkey Abhilasha , Kariuki Samuel , Kingsley Robert A , Koshy Roshine Mary , Lauer AC , Levine Myron M , Lingegowda Ravikumar Kadahalli , Luby Stephen P , Mackenzie Grant Austin , Mashe Tapfumanei , Msefula Chisomo , Mutreja Ankur , Nagaraj Geetha , Nagaraj Savitha , Nair Satheesh , Naseri Take K , Nimarota-Brown Susana , Njamkepo Elisabeth , Okeke Iruka N , Perumal Sulochana Putli Bai , Pollard Andrew J , Pragasam Agila Kumari , Qadri Firdausi , Qamar Farah N , Rahman Sadia Isfat Ara , Rambocus Savitra Devi , Rasko David A , Ray Pallab , Robins-Browne Roy , Rongsen-Chandola Temsunaro , Rutanga Jean Pierre , Saha Samir K , Saha Senjuti , Saigal Karnika , Sajib Mohammad Saiful Islam , Seidman Jessica C , Shakya Jivan , Shamanna Varun , Shastri Jayanthi , Shrestha Rajeev , Sia Sonia , Sikorski Michael J , Singh Ashita , Smith Anthony M , Tagg Kaitlin A , Tamrakar Dipesh , Tanmoy Arif Mohammed , Thomas Maria , Thomas Mathew S , Thomsen Robert , Thomson Nicholas R , Tupua Siaosi , Vaidya Krista , Valcanis Mary , Veeraraghavan Balaji , Weill François-Xavier , Wright Jackie , Dougan Gordon , Argimón Silvia , Keane Jacqueline A , Aanensen David M , Baker Stephen , Holt Kathryn E ,   Global Typhoid Genomics Consortium Group Authorship
Published: September 2023

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]).