Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from 13,000SalmonellaTyphi genomes

Author:

Carey Megan E.ORCID,Dyson Zoe A.ORCID,Ingle Danielle J.ORCID,Amir AfreenishORCID,Aworh Mabel K.ORCID,Chattaway Marie AnneORCID,Chew Ka LipORCID,Crump John A.ORCID,Feasey Nicholas A.ORCID,Howden Benjamin P.ORCID,Keddy Karen H.ORCID,Maes MailisORCID,Parry Christopher M.ORCID,Puyvelde Sandra Van,Webb Hattie E.ORCID,Afolayan Ayorinde O.ORCID,Anandan ShaliniORCID,Andrews Jason R.ORCID,Ashton Philip M.,Basnyat Buddha,Bavdekar Ashish,Bogoch Isaac I.ORCID,Clemens John D.ORCID,da Silva Kesia E.,De AnuradhaORCID,de Ligt JoepORCID,Diaz Guevara Paula Lucia,Dolecek ChristianeORCID,Dutta ShantaORCID,Watkins Louise FrancoisORCID,Garrett Denise O.,Godbole GauriORCID,Gordon Melita A.ORCID,Greenhill Andrew R.ORCID,Griffin ChelseyORCID,Gupta MadhuORCID,Hendricksen ReneORCID,Heyderman Robert S.ORCID,Hooda Yogesh,Hormazabal Juan Carlos,Ikhimiukor Odion O.,Iqbal JunaidORCID,Jacob Jobin J.,Jenkins ClaireORCID,Jinka Dasaratha RamaiahORCID,John JacobORCID,Kang GagandeepORCID,Kanteh AbdoulieORCID,Kapil Arti,Karkey AbhilashaORCID,Kariuki SamuelORCID,Kingsley Robert A.,Koshy Roshine MaryORCID,Lauer A. C.ORCID,Levine Myron M.ORCID,Lingegowda Ravikumar KadahalliORCID,Luby Stephen P.ORCID,Mackenzie Grant A.ORCID,Mashe Tapfumanei A.,Msefula ChisomoORCID,Mutreja Ankur,Nagaraj GeethaORCID,Nagaraj Savitha,Nair SatheeshORCID,Naseri Take K.,Nimarota-Brown Susana,Njamkepo ElisabethORCID,Okeke Iruka N.,Perumal Sulochana Putli BaiORCID,Pollard Andrew J.ORCID,Pragasam Agila Kumari,Qadri FirdausiORCID,Qamar Farah N.ORCID,Rahman Sadia Isfat AraORCID,Rambocus Savitra D.,Rasko David A.,Ray PallabORCID,Robins-Browne RoyORCID,Rongsen-Chandola TemsunaroORCID,Rutanga Jean PierreORCID,Saha Samir K.,Saha SenjutiORCID,Saigal Karnika,Sajib Mohammad Saiful IslamORCID,Seidman Jessica C.,Shakya Jivan,Shamanna VarunORCID,Shastri Jayanthi,Shrestha Rajeev,Sia Sonia,Sikorski Michael J.ORCID,Singh AshitaORCID,Smith Anthony M.ORCID,Tagg Kaitlin A.ORCID,Tamrakar DipeshORCID,Tanmoy Arif MohammadORCID,Thomas MariaORCID,Thomas Mathew S.,Thomsen Robert,Thomson Nicholas R.,Tupua Siaosi,Vaidya Krista,Valcanis Mary,Veeraraghavan Balaji,Weill François-XavierORCID,Wright JackieORCID,Dougan Gordon,Argimón SilviaORCID,Keane Jacqueline A.ORCID,Aanensen David M.ORCID,Baker StephenORCID,Holt Kathryn E.ORCID,

Abstract

AbstractThe Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyseSalmonella entericaserovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks twenty-one years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000), and provides a detailed overview of global genotype and antimicrobial resistance (AMR) distribution and temporal trends, generated using open analysis platforms (GenoTyphi and Pathogenwatch). 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 potential of travel-associated data to provide informal “sentinel” surveillance for such locations. The data indicate ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level 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. 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.

Publisher

Cold Spring Harbor Laboratory

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