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dc.contributor.authorBritto, Carl D
dc.contributor.authorDyson, Zoe A
dc.contributor.authorDuchene, Sebastian
dc.contributor.authorCarter, Michael J
dc.contributor.authorGurung, Meeru
dc.contributor.authorKelly, Dominic F
dc.contributor.authorMurdoch, David R
dc.contributor.authorAnsari, Imran
dc.contributor.authorThorson, Stephen
dc.contributor.authorShrestha, Shrijana
dc.contributor.authorAdhikari, Neelam
dc.contributor.authorDougan, Gordon
dc.contributor.authorHolt, Kathryn E
dc.contributor.authorPollard, Andrew J
dc.date.accessioned2018-09-08T06:29:26Z
dc.date.available2018-09-08T06:29:26Z
dc.date.issued2018-04
dc.identifier.issn1935-2727
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279757
dc.description.abstractBACKGROUND: Children are substantially affected by enteric fever in most settings with a high burden of the disease, including Nepal. However pathogen population structure and transmission dynamics are poorly delineated in young children, the proposed target group for immunization programs. Here we present whole genome sequencing and antimicrobial susceptibility data on 198 S. Typhi and 66 S. Paratyphi A isolated from children aged 2 months to 15 years of age during blood culture surveillance at Patan Hospital, Nepal, 2008-2016. PRINCIPAL FINDINGS: S. Typhi was the dominant agent and comprised several distinct genotypes, dominated by 4.3.1 (H58). The heterogeneity of genotypes in children under five was reduced compared to data from 2005-2006, attributable to ongoing clonal expansion of H58. Most isolates (86%) were non-susceptible to fluoroquinolones, associated mainly with S. Typhi H58 lineage II and S. Paratyphi A harbouring mutations in the quinolone resistance-determining region (QRDR); non-susceptible strains from these groups accounted for 50% and 25% of all isolates. Multi-drug resistance (MDR) was rare (3.5% of S. Typhi, 0 S. Paratyphi A) and restricted to chromosomal insertions of resistance genes in H58 lineage I strains. Temporal analyses revealed a shift in dominance from H58 Lineage I to H58 Lineage II, with the latter being significantly more common after 2010. Comparison to global data sets showed the local S. Typhi and S. Paratyphi A strains had close genetic relatives in other South Asian countries, indicating regional strain circulation. Multiple imports from India of ciprofloxacin-resistant H58 lineage II strains were identified, but these were rare and showed no evidence of clonal replacement of local S. Typhi. SIGNIFICANCE: These data indicate that enteric fever in Nepal continues to be a major public health issue with ongoing inter- and intra-country transmission, and highlights the need for regional coordination of intervention strategies. The absence of a S. Paratyphi A vaccine is cause for concern, given its prevalence as a fluoroquinolone resistant enteric fever agent in this setting.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectSalmonella typhi
dc.subjectTyphoid Fever
dc.subjectFluoroquinolones
dc.subjectCiprofloxacin
dc.subjectTyphoid-Paratyphoid Vaccines
dc.subjectAnti-Infective Agents
dc.subjectDrug Resistance, Bacterial
dc.subjectGenotype
dc.subjectAdolescent
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectNepal
dc.subjectFemale
dc.subjectMale
dc.titleLaboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy.
dc.typeArticle
prism.issueIdentifier4
prism.publicationDate2018
prism.publicationNamePLoS Negl Trop Dis
prism.startingPagee0006408
prism.volume12
dc.identifier.doi10.17863/CAM.27127
dcterms.dateAccepted2018-03-25
rioxxterms.versionofrecord10.1371/journal.pntd.0006408
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-04-23
dc.contributor.orcidBritto, Carl D [0000-0002-1674-8801]
dc.contributor.orcidDyson, Zoe A [0000-0002-8887-3492]
dc.contributor.orcidCarter, Michael J [0000-0003-3403-4746]
dc.contributor.orcidGurung, Meeru [0000-0003-4366-6403]
dc.contributor.orcidThorson, Stephen [0000-0002-9546-6406]
dc.contributor.orcidDougan, Gordon [0000-0003-0022-965X]
dc.contributor.orcidHolt, Kathryn E [0000-0003-3949-2471]
dc.identifier.eissn1935-2735
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (106158/Z/14/Z)
cam.issuedOnline2018-04-23


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Attribution 4.0 International (CC BY 4.0)
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