Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: A cross-sectional study

Kate S. Baker, Tim Dallman, Philip M. Ashton, Martin Day, Gwenda Hughes, Paul Crook, Victoria L. Gilbart, Sandra Zittermann, Vanessa G. Allen, Benjamin P. Howden, Takehiro Tomita, Mary Valcanis, Simon R. Harris, Thomas R. Connor, Vitali Sintchenko, Peter Howard, Jeremy D. Brown, Nicola K. Petty, Malika Gouali, Duy Pham ThanhKaren H. Keddy, Anthony M. Smith, Kaisar A. Talukder, Shah M. Faruque, Julian Parkhill, Stephen Baker, François Xavier Weill, Claire Jenkins, Nicholas R. Thomson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

199 Citations (Scopus)

Abstract

Background: Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK. Methods: We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships. Findings: We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated atypical infection patterns (eg, reinfection). Interpretation: We identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM. Funding: Wellcome Trust (grant number 098051).

Original languageEnglish
Pages (from-to)913-921
Number of pages9
JournalThe Lancet Infectious Diseases
Volume15
Issue number8
DOIs
Publication statusPublished - 1 Aug 2015

Bibliographical note

Funding Information:
We are grateful to staff at the Wellcome Trust Sanger Institute (WTSI), including David Harris, Theresa Feltwell, Derek Pickard, and core members of the sequencing and informatics teams, as well as Alison Mather for bioinformatics training. The authors also thank the anonymous reviewers and Estee Torok for helpful comments on the report. Wellcome Trust grant number 098051 funded authors from the WTSI. We thank Isabelle Carle, Monique Lejay-Collin, and Corinne Ruckly from the Pasteur Institute for their excellent technical assistance. The Institut Pasteur authors are funded by the Institut Pasteur, the Institut de Veille Sanitaire, and by the French Government “Investissement d'Avenir” programme (Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, grant number ANR-10-LABX-62-IBEID). VS was supported by the Australian National Health and Medical Research Council's Career Development Award. We acknowledge the expert technical assistance of Alex Kuzevski for isolate characterisation at The University of Melbourne, which is funded by the Department of Health in Victoria, Australia. SB is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (100087/Z/12/Z). BPH is supported by a Fellowship from the National Health and Medical Research Council, Australia ( APP1023526 ).

Funding Information:
KSB, NRT, SRH, and JP report grants from the Wellcome Trust during the conduct of the study. JP declares non-financial support from Illumina, outside the submitted work. All other authors declare no competing interests.

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