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dc.contributor.authorBritto, CD
dc.contributor.authorDyson, ZA
dc.contributor.authorDuchene, S
dc.contributor.authorCarter, MJ
dc.contributor.authorGurung, M
dc.contributor.authorKelly, DF
dc.contributor.authorMurdoch, DR
dc.contributor.authorAnsari, I
dc.contributor.authorThorson, S
dc.contributor.authorShrestha, S
dc.contributor.authorAdhikari, N
dc.contributor.authorDougan, G
dc.contributor.authorHolt, KE
dc.contributor.authorPollard, AJ
dc.date.accessioned2020-12-17T03:38:21Z
dc.date.available2020-12-17T03:38:21Z
dc.date.issued2018-04-01
dc.identifierpii: PNTD-D-18-00081
dc.identifier.citationBritto, C. D., Dyson, Z. A., Duchene, S., Carter, M. J., Gurung, M., Kelly, D. F., Murdoch, D. R., Ansari, I., Thorson, S., Shrestha, S., Adhikari, N., Dougan, G., Holt, K. E. & Pollard, A. J. (2018). Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy. PLOS NEGLECTED TROPICAL DISEASES, 12 (4), https://doi.org/10.1371/journal.pntd.0006408.
dc.identifier.issn1935-2735
dc.identifier.urihttp://hdl.handle.net/11343/254968
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.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.titleLaboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pntd.0006408
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titlePLoS Neglected Tropical Diseases
melbourne.source.volume12
melbourne.source.issue4
dc.rights.licenseCC BY
melbourne.elementsid1325537
melbourne.contributor.authorDyson, Zoe
melbourne.contributor.authorHolt, Kathryn
melbourne.contributor.authorDuchene Garzon, Sebastian
melbourne.contributor.authorDougan, Gordon
dc.identifier.eissn1935-2735
melbourne.accessrightsOpen Access


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