학술논문

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Document Type
article
Author
Megan E CareyZoe A DysonDanielle J IngleAfreenish AmirMabel K AworhMarie Anne ChattawayKa Lip ChewJohn A CrumpNicholas A FeaseyBenjamin P HowdenKaren H KeddyMailis MaesChristopher M ParrySandra Van PuyveldeHattie E WebbAyorinde Oluwatobiloba AfolayanAnna P AlexanderShalini AnandanJason R AndrewsPhilip M AshtonBuddha BasnyatAshish BavdekarIsaac I BogochJohn D ClemensKesia Esther da SilvaAnuradha DeJoep de LigtPaula Lucia Diaz GuevaraChristiane DolecekShanta DuttaMarthie M EhlersLouise Francois WatkinsDenise O GarrettGauri GodboleMelita A GordonAndrew R GreenhillChelsey GriffinMadhu GuptaRene S HendriksenRobert S HeydermanYogesh HoodaJuan Carlos HormazabalOdion O IkhimiukorJunaid IqbalJobin John JacobClaire JenkinsDasaratha Ramaiah JinkaJacob JohnGagandeep KangAbdoulie KantehArti KapilAbhilasha KarkeySamuel KariukiRobert A KingsleyRoshine Mary KoshyAC LauerMyron M LevineRavikumar Kadahalli LingegowdaStephen P LubyGrant Austin MackenzieTapfumanei MasheChisomo MsefulaAnkur MutrejaGeetha NagarajSavitha NagarajSatheesh NairTake K NaseriSusana Nimarota-BrownElisabeth NjamkepoIruka N OkekeSulochana Putli Bai PerumalAndrew J PollardAgila Kumari PragasamFirdausi QadriFarah N QamarSadia Isfat Ara RahmanSavitra Devi RambocusDavid A RaskoPallab RayRoy Robins-BrowneTemsunaro Rongsen-ChandolaJean Pierre RutangaSamir K SahaSenjuti SahaKarnika SaigalMohammad Saiful Islam SajibJessica C SeidmanJivan ShakyaVarun ShamannaJayanthi ShastriRajeev ShresthaSonia SiaMichael J SikorskiAshita SinghAnthony M SmithKaitlin A TaggDipesh TamrakarArif Mohammed TanmoyMaria ThomasMathew S ThomasRobert ThomsenNicholas R ThomsonSiaosi TupuaKrista VaidyaMary ValcanisBalaji VeeraraghavanFrançois-Xavier WeillJackie WrightGordon DouganSilvia ArgimónJacqueline A KeaneDavid M AanensenStephen BakerKathryn E HoltGlobal Typhoid Genomics Consortium Group Authorship
Source
eLife, Vol 12 (2023)
Subject
genomics
typhoid fever
antimicrobial resistance
typhoid conjugate vaccine
Medicine
Science
Biology (General)
QH301-705.5
Language
English
ISSN
2050-084X
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]).