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Whole-genome sequencing to determine transmission of Neisseria gonorrhoeae: an observational study

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Title: Whole-genome sequencing to determine transmission of Neisseria gonorrhoeae: an observational study
Authors: De Silva, D
Peters, J
Cole, K
Cole, MJ
Cresswell, F
Dean, G
Dave, J
Thomas, DR
Foster, K
Waldram, A
Wilson, DJ
Didelot, X
Grad, YH
Crook, DW
Peto, TE
Walker, AS
Paul, J
Eyre, DW
Item Type: Journal Article
Abstract: BACKGROUND: New approaches are urgently required to address increasing rates of gonorrhoea and the emergence and global spread of antibiotic-resistant Neisseria gonorrhoeae. We used whole-genome sequencing to study transmission and track resistance in N gonorrhoeae isolates. METHODS: We did whole-genome sequencing of isolates obtained from samples collected from patients attending sexual health services in Brighton, UK, between Jan 1, 2011, and March 9, 2015. We also included isolates from other UK locations, historical isolates from Brighton, and previous data from a US study. Samples from symptomatic patients and asymptomatic sexual health screening underwent nucleic acid amplification testing; positive samples and all samples from symptomatic patients were cultured for N gonorrhoeae, and resulting isolates were whole-genome sequenced. Cefixime susceptibility testing was done in selected isolates by agar incorporation, and we used sequence data to determine multi-antigen sequence types and penA genotypes. We derived a transmission nomogram to determine the plausibility of direct or indirect transmission between any two cases depending on the time between samples: estimated mutation rates, plus diversity noted within patients across anatomical sites and probable transmission pairs, were used to fit a coalescent model to determine the number of single nucleotide polymorphisms expected. FINDINGS: 1407 (98%) of 1437 Brighton isolates between Jan 1, 2011, and March 9, 2015 were successfully sequenced. We identified 1061 infections from 907 patients. 281 (26%) of these infections were indistinguishable (ie, differed by zero single nucleotide polymorphisms) from one or more previous cases, and 786 (74%) had evidence of a sampled direct or indirect Brighton source. We observed multiple related samples across geographical locations. Of 1273 infections in Brighton (including historical data), 225 (18%) were linked to another case elsewhere in the UK, and 115 (9%) to a case in the USA. Four lineages initially identified in Brighton could be linked to 70 USA sequences, including 61 from a lineage carrying the mosaic penA XXXIV allele, which is associated with reduced cefixime susceptibility. INTERPRETATION: We present a whole-genome-sequencing-based tool for genomic contact tracing of N gonorrhoeae and demonstrate local, national, and international transmission. Whole-genome sequencing can be applied across geographical boundaries to investigate gonorrhoea transmission and to track antimicrobial resistance. FUNDING: Oxford National Institute for Health Research Health Protection Research Unit and Biomedical Research Centre.
Issue Date: 1-Nov-2016
Date of Acceptance: 1-Jul-2016
URI: http://hdl.handle.net/10044/1/60215
DOI: https://dx.doi.org/10.1016/S1473-3099(16)30157-8
ISSN: 1473-3099
Publisher: Elsevier: Lancet
Start Page: 1295
End Page: 1303
Journal / Book Title: Lancet Infectious Diseases
Volume: 11
Issue: 11
Copyright Statement: © 2016 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/K010174/1B
Keywords: Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Anti-Bacterial Agents
Cephalosporin Resistance
Microbial Sensitivity Tests
Neisseria gonorrhoeae
Retrospective Studies
Sequence Analysis, DNA
United Kingdom
1103 Clinical Sciences
1108 Medical Microbiology
Publication Status: Published
Open Access location: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086424/pdf/emss-70025.pdf
Online Publication Date: 2016-07-11
Appears in Collections:School of Public Health