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dc.contributor.authorRahman, Sadia Isfat Ara
dc.contributor.authorDyson, Zoe A.
dc.contributor.authorKlemm, Elizabeth J.
dc.contributor.authorKhanam, Farhana
dc.contributor.authorHolt, Kathryn E.
dc.contributor.authorChowdhury, Emran Kabir
dc.contributor.authorDougan, Gordon
dc.contributor.authorQadri, Firdausi
dc.date.accessioned2020-03-11T03:15:10Z
dc.date.available2020-03-11T03:15:10Z
dc.date.issued2020-02-27
dc.date.submitted2019-07-03
dc.identifier.otherpntd-d-19-01039
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303293
dc.description.abstractBackground: Multi-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the epidemiology and genomics of S. Typhi in many regions. Here we have undertaken a detailed genomic analysis of typhoid in urban Dhaka, Bangladesh to unravel the population structure and antimicrobial resistance patterns in S. Typhi isolated between 2004–2016. Principal findings: Whole genome sequencing of 202 S. Typhi isolates obtained from three study locations in urban Dhaka revealed a diverse range of S. Typhi genotypes and AMR profiles. The bacterial population within Dhaka were relatively homogenous with little stratification between different healthcare facilities or age groups. We also observed evidence of exchange of Bangladeshi genotypes with neighboring South Asian countries (India, Pakistan and Nepal) suggesting these are circulating throughout the region. This analysis revealed a decline in H58 (genotype 4.3.1) isolates from 2011 onwards, coinciding with a rise in a diverse range of non-H58 genotypes and a simultaneous rise in isolates with reduced susceptibility to fluoroquinolones, potentially reflecting a change in treatment practices. We identified a novel S. Typhi genotype, subclade 3.3.2 (previously defined only to clade level, 3.3), which formed two localized clusters (3.3.2.Bd1 and 3.3.2.Bd2) associated with different mutations in the Quinolone Resistance Determining Region (QRDR) of gene gyrA. Significance: Our analysis of S. Typhi isolates from urban Dhaka, Bangladesh isolated over a twelve year period identified a diverse range of AMR profiles and genotypes. The observed increase in non-H58 genotypes associated with reduced fluoroquinolone susceptibility may reflect a change in treatment practice in this region and highlights the importance of continued molecular surveillance to monitor the ongoing evolution of AMR in Dhaka. We have defined new genotypes and lineages of Bangladeshi S. Typhi which will facilitate the identification of these emerging AMR clones in future surveillance efforts.
dc.languageen
dc.publisherPublic Library of Science
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectMedicine and health sciences
dc.subjectBiology and life sciences
dc.subjectPeople and places
dc.subjectComputer and information sciences
dc.titlePopulation structure and antimicrobial resistance patterns of Salmonella Typhi isolates in urban Dhaka, Bangladesh from 2004 to 2016
dc.typeArticle
dc.date.updated2020-03-11T03:15:09Z
prism.issueIdentifier2
prism.publicationNamePLOS Neglected Tropical Diseases
prism.volume14
dc.identifier.doi10.17863/CAM.50377
dcterms.dateAccepted2020-01-08
rioxxterms.versionofrecord10.1371/journal.pntd.0008036
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Senok, Abiola
dc.contributor.orcidDyson, Zoe A. [0000-0002-8887-3492]
dc.contributor.orcidHolt, Kathryn E. [0000-0003-3949-2471]
dc.identifier.eissn1935-2735
pubs.funder-project-idWellcome Trust (106158/Z/14/Z)
pubs.funder-project-idNational Institute of Allergy and Infectious Diseases (AI100023,AI058935)
pubs.funder-project-idFogarty International Center Training Grant in Vaccine Development and Public Health (TW005572)
pubs.funder-project-idBill and Melinda Gates Foundation (OPP50419)
pubs.funder-project-idSIDA (54100020, 51060029)
pubs.funder-project-idWellcome Trust (098051)
pubs.funder-project-idBill and Melinda Gates Foundation (OPP1151153)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)