1887

Abstract

Since the 1970s, shigellosis has been reported as a sexually transmissible infection, and in recent years, genomic data have revealed the breadth of spp. transmission among global networks of men who have sex with men (MSM). In 2015, Public Health England (PHE) introduced routine whole-genome sequencing (WGS) of spp. to identify transmission clusters. However, limited behavioural information for the cases hampers interpretation. We investigated whether WGS can distinguish between clusters representing sexual transmission in MSM and clusters representing community (non-sexual) transmission to inform infection control. WGS data for from August 2015 to July 2017 were aggregated into single linkage clusters based on SNP typing using a range of SNP distances (the standard for surveillance at PHE is 10 SNPs). Clusters were classified as ‘adult male’, ‘household’, ‘travel-associated’ or ‘community’ using routine demographic data submitted alongside laboratory cultures. From August 2015 to March 2017, PHE contacted those with shigellosis as part of routine public-health follow-up and collected exposure data on a structured questionnaire, which for the first time included questions about sexual identity and behaviour. The questionnaire data were used to determine whether clusters classified as ‘adult male’ represented likely sexual transmission between men, thereby validating the use of the SNP clustering tool for informing appropriate public-health responses. Overall, 1006 . cases were reported, of which 563 clustered with at least one other case (10-SNP threshold). Linked questionnaire data were available for 106 clustered cases, of which 84.0 % belonged to an ‘adult male’ cluster. At the 10-SNP threshold, 95.1 % [95 % confidence interval (CI) 88.0–98.1%] of MSM belonged to an ‘adult male’ cluster, while 73.2 % (95 % CI 49.1–87.5%) of non-MSM belonged to a ‘community’ or ‘travel-associated’ cluster. At the 25-SNP threshold, all MSM (95 % CI 96.0–100%) belonged to an ‘adult male’ cluster and 77.8 % (95 % CI 59.2–89.4%) of non-MSM belonged to a ‘community’ or ‘travel-associated’ cluster. Within one phylogenetic clade of , 9 clusters were identified (7 ‘adult male’; 2 ‘community’) using a 10-SNP threshold, while a single ‘adult male’ cluster was identified using a 25-SNP threshold. Genotypic markers of azithromycin resistance were detected in 84.5 % (294/348) of ‘adult male’ cases and 20.9 % (9/43) of cases in other clusters (10-SNP threshold), the latter of which contained gay-identifying men who reported recent same-sex sexual contact. Our study suggests that SNP clustering can be used to identify clusters representing likely sexual transmission in MSM to inform infection control. Defining clusters requires a flexible approach in terms of genetic relatedness to ensure a clear understanding of underlying transmission networks.

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2019-11-04
2019-11-21
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References

  1. Kotloff KL, Winickoff JP, Ivanoff B, Clemens JD, Swerdlow DL et al. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ 1999;77: 651– 666
    [Google Scholar]
  2. Livio S, Strockbine NA, Panchalingam S, Tennant SM, Barry EM et al. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis 2014;59: 933– 941 [CrossRef]
    [Google Scholar]
  3. GBD Diarrhoeal Diseases Collaborators Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the global burden of disease study 2015. Lancet Infect Dis 2017;17: 909– 948 [CrossRef]
    [Google Scholar]
  4. Baker KS, Dallman TJ, Ashton PM, Day M, Hughes G et al. Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study. Lancet Infect Dis 2015;15: 913– 921 [CrossRef]
    [Google Scholar]
  5. Simms I, Field N, Jenkins C, Childs T, Gilbart VL et al. Intensified shigellosis epidemic associated with sexual transmission in men who have sex with men – Shigella flexneri and S. sonnei in England, 2004 to end of February 2015. Euro Surveill 2015;20: 21097 [CrossRef]
    [Google Scholar]
  6. Gilbart VL, Simms I, Jenkins C, Furegato M, Gobin M et al. Sex, drugs and smart phone applications: findings from semistructured interviews with men who have sex with men diagnosed with Shigella flexneri 3a in England and Wales. Sex Transm Infect 2015;91: 598– 602 [CrossRef]
    [Google Scholar]
  7. Baker KS, Dallman TJ, Field N, Childs T, Mitchell H et al. Genomic epidemiology of Shigella in the United Kingdom shows transmission of pathogen sublineages and determinants of antimicrobial resistance. Sci Rep 2018;8: 7389 [CrossRef]
    [Google Scholar]
  8. Baker KS, Dallman TJ, Field N, Childs T, Mitchell H et al. Horizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species. Nat Commun 2018;9: 1462 [CrossRef]
    [Google Scholar]
  9. Dallman TJ, Chattaway MA, Mook P, Godbole G, Crook PD et al. Use of whole-genome sequencing for the public health surveillance of Shigella sonnei in England and Wales, 2015. J Med Microbiol 2016;65: 882– 884 [CrossRef]
    [Google Scholar]
  10. Chattaway MA, Greig DR, Gentle A, Hartman HB, Dallman TJ et al. Whole-genome sequencing for national surveillance of Shigella flexneri. Front Microbiol 2017;8: 1700 [CrossRef]
    [Google Scholar]
  11. Dallman T, Ashton P, Schafer U, Jironkin A, Painset A et al. SnapperDB: a database solution for routine sequencing analysis of bacterial isolates. Bioinformatics 2018;34: 3028– 3029 [CrossRef]
    [Google Scholar]
  12. The National Archive The Health Protection (Notification) Regulations 2010, no. 659 London: The Stationary Office; 2010
    [Google Scholar]
  13. Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv 2013; 1303.3997
    [Google Scholar]
  14. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009;25: 2078– 2079 [CrossRef]
    [Google Scholar]
  15. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010;20: 1297– 1303 [CrossRef]
    [Google Scholar]
  16. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015;43: e15 [CrossRef]
    [Google Scholar]
  17. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014;30: 1312– 1313 [CrossRef]
    [Google Scholar]
  18. Letunic I, Bork P. Interactive Tree of Life (iTOL) V3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res 2016;44: W242– W245 [CrossRef]
    [Google Scholar]
  19. Letunic I, Bork P. Interactive Tree of Life (iTOL) V4: recent updates and new developments. Nucleic Acids Res 2019;47: W256– W259 [CrossRef]
    [Google Scholar]
  20. Doumith M, Godbole G, Ashton P, Larkin L, Dallman T et al. Detection of the plasmid-mediated mcr-1 gene conferring colistin resistance in human and food isolates of Salmonella enterica and Escherichia coli in England and Wales. J Antimicrob Chemother 2016;71: 2300– 2305 [CrossRef]
    [Google Scholar]
  21. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods 2012;9: 357– 359 [CrossRef]
    [Google Scholar]
  22. Public Health England and the Chartered Institute of Environmental Health P rinciples and Practice Recommendations for the Public Health Management of Gastrointestinal Infections London: Public Health England; 2018
    [Google Scholar]
  23. Public Health England Producing Modelled Estimates of the Size of the Lesbian, Gay and Bisexual (LGB) Population of England London: Public Health England; 2017; https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/585349/PHE_Final_report_FINAL_DRAFT_14.12.2016NB230117v2.pdf
    [Google Scholar]
  24. Public Health England Laboratory Surveillance of Non-travel Associated Shigella spp. Infection in Adult Males, England: 2004 to 2017, Health Protection Report vol. 11 no. 42 London: Public Health England; 2017
    [Google Scholar]
  25. Mook P, Gardiner D, Kanagarajah S, Kerac M, Hughes G et al. Use of gender distribution in routine surveillance data to detect potential transmission of gastrointestinal infections among men who have sex with men in England. Epidemiol Infect 2018;146: 1468– 1477 [CrossRef]
    [Google Scholar]
  26. Tam CC, Rodrigues LC, O'Brien SJ. The study of infectious intestinal disease in England: what risk factors for presentation to general practice tell us about potential for selection bias in case-control studies of reported cases of diarrhoea. Int J Epidemiol 2003;32: 99– 105 [CrossRef]
    [Google Scholar]
  27. McCrickard LS, Crim SM, Kim S, Bowen A. Disparities in severe shigellosis among adults - foodborne diseases active surveillance network, 2002-2014. BMC Public Health 2018;18: 221 [CrossRef]
    [Google Scholar]
  28. Sewell J, Miltz A, Lampe FC, Cambiano V, Speakman A et al. Poly drug use, chemsex drug use, and associations with sexual risk behaviour in HIV-negative men who have sex with men attending sexual health clinics. Int J Drug Policy 2017;43: 33– 43 [CrossRef]
    [Google Scholar]
  29. Hughes G, Alexander S, Simms I, Conti S, Ward H et al. Lymphogranuloma venereum diagnoses among men who have sex with men in the UK: interpreting a cross-sectional study using an epidemic phase-specific framework. Sex Transm Infect 2013;89: 542– 547 [CrossRef]
    [Google Scholar]
  30. Fenton KA, Imrie J. Increasing rates of sexually transmitted diseases in homosexual men in Western Europe and the United States: why?. Infect Dis Clin North Am 2005;19: 311– 331 [CrossRef]
    [Google Scholar]
  31. Clutterbuck D, Asboe D, Barber T, Emerson C, Field N et al. 2016 United Kingdom national guideline on the sexual health care of men who have sex with men. Int J STD AIDS doi:10.1177/0956462417746897 [Epub ahead of print]
    [Google Scholar]
  32. Public Health England Update on the Epidemiology of Shigella in Adults in London, 2012 to 2016: Excess of Cases in Men Who Have Sex With Men London: Public Health England; 2017
    [Google Scholar]
  33. Kanagarajah S, Waldram A, Dolan G, Jenkins C, Ashton PM et al. Whole genome sequencing reveals an outbreak of Salmonella enteritidis associated with reptile feeder mice in the United Kingdom, 2012-2015. Food Microbiol 2018;71: 32– 38 [CrossRef]
    [Google Scholar]
  34. Waldram A, Dolan G, Ashton PM, Jenkins C, Dallman TJ. Epidemiological analysis of Salmonella clusters identified by whole genome sequencing, England and Wales 2014. Food Microbiol 2018;71: 39– 45 [CrossRef]
    [Google Scholar]
  35. Rew V, Mook P, Trienekens S, Baker KS, Dallman TJ et al. Whole-genome sequencing revealed concurrent outbreaks of shigellosis in the English Orthodox Jewish Community caused by multiple importations of Shigella sonnei from Israel. Microb Genom 2018;4: mgen.0.000170 [CrossRef]
    [Google Scholar]
  36. Connor TR, Barker CR, Baker KS, Weill FX, Talukder KA et al. Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri. eLife 2015;4: e07335 [CrossRef]
    [Google Scholar]
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