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 Kamweli Aworh, Marie Anne Chattaway, Ka Lip Chew, John A. Crump, Nicholas Feasey, Benjamin P. Howden, Karen H. Keddy, Mailis Maes, Christopher M. Parry, Sandra Van Puyvelde, Hattie E. Webb, Ayorinde O. Afolayan, Anna P. Alexander, Shalini Anandan, Jason R. Andrews, Philip Ashton, Buddha Basnyat, Ashish Bavdekar, Isaac I. Bogoch, John D. Clemens, Késia Esther da Silva, Anuradha De, Joep de Ligt, Paula Díaz, 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, René S. Hendriksen, Robert S. Heyderman, Yogesh Hooda, Juan Carlos Hormazábal, Odion O. Ikhimiukor, Junaid Iqbal, Jobin John Jacob, Claire Jenkins, Dasaratha Ramaiah Jinka, Jacob John, Gagandeep Kang, Abdoulie Kanteh, Arti Kapil, Abhilasha Karkey, Samuel Kariuki, Robert A. Kingsley, Roshine Mary Koshy, A.C. Lauer, Myron M. Levine, Ravikumar Kadahalli Lingegowda, Stephen P. Luby, Grant Mackenzie, Tapfumanei Mashe, Chisomo Msefula, Ankur Mutreja, Geetha Nagaraj, Savitha Nagaraj, Satheesh Nair, Take Naseri, Susana Nimarota-Brown, Elisabeth Njamkepo, Iruka N. Okeke, Sulochana Putli Bai Perumal, Andrew J. Pollard, Agila Kumari Pragasam, Firdausi Qadri, Farah Naz Qamar, Sadia Rahman, Savitra Rambocus, David A. Rasko, Pallab Ray, Roy M. Robins‐Browne, Temsunaro Rongsen‐Chandola, Jean Pierre Rutanga, Samir K. Saha, Senjuti Saha, Karnika Saigal, Mohammad Saiful Islam Sajib, Jessica C. Seidman, Jivan Shakya, Varun Shamanna, Jayanthi Shastri, Rajeev Shrestha, Sonia Sia, Michael J. Sikorski, Ashita Singh, Anthony M. Smith, Kaitlin A. Tagg, Dipesh Tamrakar, Arif Mohammad Tanmoy, Maria Thomas, M. Thomas
Abstract
Background: 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]).