Abstract
Since the 1970s, shigellosis has been reported as a sexually transmissible infection, and in recent years, genomic data have revealed the breadth of Shigella 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 Shigella 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 Shigella flexneri 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 Shigella 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 S. flexneri 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 S. flexneri, 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 Shigella 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.
| Original language | English |
|---|---|
| Article number | 000311 |
| Journal | Microbial Genomics |
| Volume | 5 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2019 |
Bibliographical note
Funding Information:No specific consent was required from the patients whose data were used in this analysis. This is because PHE has authority to handle patient data for public-health monitoring and infection control under section 251 of the UK National Health Service Act of 2006 (previously section 60 of the Health and Social Care Act of 2001), which was reviewed annually by the ethics and confidentiality committee of the National Information Governance Board until 2013. Since then, the power of approval of public-health surveillance activity has been granted directly to PHE. This study was approved by the PHE Research Support and Governance Office and Caldicott Panel in June 2017.
Funding Information:
Received 09 July 2019; Accepted 15 October 2019; Published 04 November 2019 Author affiliations: 1Centre for Molecular Epidemiology and Translational Research, Institute for Global Health, University College London, London, UK; 2National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections, London, UK; 3National Infection Service, Public Health England, London, UK; 4National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections, Liverpool, UK; 5Parasites and Microbes, Wellcome Trust Sanger Institute, Hinxton, UK; 6Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, UK. *Correspondence: Holly D. Mitchell, [email protected] Keywords: whole-genome sequencing; surveillance; England; Shigella. Abbreviations: CC, clonal complex; CI, confidence interval; GBRU, Gastrointestinal Bacteria Reference Unit; HIV, human immunodeficiency virus; HPRU, Health Protection Research Unit; HPT, Health Protection Team; MSM, men who have sex with men; NIHR, National Institute for Health Research; PHE, Public Health England; WGS, whole-genome sequencing. †These authors contributed equally to this work Data statement: All supporting data, code and protocols have been provided within the article or through supplementary data files. Supplementary material is available with the online version of this article.
Funding Information:
This research was conducted through the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections at University College London in partnership with PHE, in collaboration with the London School of Hygiene and Tropical Medicine, and the NIHR HPRU in Gastrointestinal Infections at the University of Liverpool in partnership with PHE, in collaboration with the University of East Anglia, the University of Oxford and the Quadram Institute.
Funding Information:
H. D. M. and G. H. are affiliated to the NIHR HPRU in Blood Borne and Sexually Transmitted Infections at University College London in partnership with PHE, in collaboration with the London School of Hygiene and Tropical Medicine. A. P., T. J. D. and C. J. are affiliated to the NIHR HPRU in Gastrointestinal Infections at the University of Liverpool in partnership with PHE, in collaboration with the University of East Anglia, the University of Oxford and the Quadram Institute (109524). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care or PHE.. The authors would like to thank colleagues at the HPTs and Environmental Health Departments who were involved in the pilot of the standardized questionnaire, and members of the Shigella guidance working group. We would also like to thank John Were and Rachel Glass for support with data collection, and Tracey Cairns and Krishna Gupta for data entry support. We acknowledge the support of the steering committee members of the NIHR HPRU in Blood Borne and Sexually Transmitted Infections: Caroline Sabin (Director), John Saunders (PHE Lead), Catherine Mercer, Gwenda Hughes, Jackie Cassell, Greta Rait, Samreen Ijaz, Tim Rhodes, Kholoud Porter, Sema Mandal and William Rosenberg.
Publisher Copyright:
© 2019 Crown.
Keywords
- England
- Shigella
- Surveillance
- Whole-genome sequencing
