Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes.
Carey ME., Dyson ZA., Ingle DJ., Amir A., Aworh MK., Chattaway MA., Chew KL., Crump JA., Feasey NA., Howden BP., Keddy KH., Maes M., Parry CM., Van Puyvelde S., Webb HE., Afolayan AO., Alexander AP., Anandan S., Andrews JR., Ashton PM., Basnyat B., Bavdekar A., Bogoch II., Clemens JD., da Silva KE., De A., de Ligt J., Diaz Guevara PL., Dolecek C., Dutta S., Ehlers MM., Francois Watkins L., Garrett DO., Godbole G., Gordon MA., Greenhill AR., Griffin C., Gupta M., Hendriksen RS., Heyderman RS., Hooda Y., Hormazabal JC., Ikhimiukor OO., Iqbal J., Jacob JJ., Jenkins C., Jinka DR., John J., Kang G., Kanteh A., Kapil A., Karkey A., Kariuki S., Kingsley RA., Koshy RM., Lauer AC., Levine MM., Lingegowda RK., Luby SP., Mackenzie GA., Mashe T., Msefula C., Mutreja A., Nagaraj G., Nagaraj S., Nair S., Naseri TK., Nimarota-Brown S., Njamkepo E., Okeke IN., Perumal SPB., Pollard AJ., Pragasam AK., Qadri F., Qamar FN., Rahman SIA., Rambocus SD., Rasko DA., Ray P., Robins-Browne R., Rongsen-Chandola T., Rutanga JP., Saha SK., Saha S., Saigal K., Sajib MSI., Seidman JC., Shakya J., Shamanna V., Shastri J., Shrestha R., Sia S., Sikorski MJ., Singh A., Smith AM., Tagg KA., Tamrakar D., Tanmoy AM., Thomas M., Thomas MS., Thomsen R., Thomson NR., Tupua S., Vaidya K., Valcanis M., Veeraraghavan B., Weill F-X., Wright J., Dougan G., Argimón S., Keane JA., Aanensen DM., Baker S., Holt KE., Global Typhoid Genomics Consortium Group Authorship None.
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 (126.96.36.199.1) 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]).