The spread of sexually transmissible drug-resistant shigellosis in England: a genomic epidemiology study

Background: Shigellosis, caused by Shigella bacteria, is a leading cause of diarrhoeal disease globally. In the last two decades, Shigella circulation in high-income countries has expanded from being a sporadic travel-associated illness to also being an endemic sexually transmissible illness among men who have sex with men (MSM). We aimed to characterise the nature and drivers of this multimodal Shigella transmission in a high-income setting. Methods: In this genomic epidemiology study, we used Shigella sonnei isolates referred for national surveillance from 138 laboratories across 15 UK health regions. Cases that had recent (defined as in the past 28 days) travel to Africa, Asia, or Latin America and the Caribbean were defined as high-risk travel-associated cases. Presumptive MSM (pMSM) cases were defined as men aged 16–60 years without recent high-risk travel history. Non-pMSM were defined as cases that were not pMSM or high-risk travel. We implemented phylodynamic and geospatial modelling on national genomic surveillance data of S sonnei isolates collected in the UK between Sept 20, 2004, and Feb 28, 2020, to quantitate and compare geospatial spread and transmission intensity of S sonnei across demographic groups (the primary outcome). We also determined the relative influence of antimicrobial resistance on pathogen dynamics in these demographic groups and evaluate the emergence of an extensively drug-resistant S sonnei clade collected in England between Jan 1, 2016, and Dec 30, 2021, as a secondary analysis. Findings: 3514 isolates were collected during the study period. Of these isolates, 1197 (34·1%) came from pMSM, 1269 (36·1%) from non-pMSM, and 1048 (29·8%) from high-risk travel. We found that sexually transmitted S sonnei spread more rapidly (ie, had a greater mean pairwise spatial distance after 2·5 years or less of evolutionary time: pMSM 117·4 km [95% CI 100·7–132·3], non-pMSM 45·8 km [32·6–62·1], p<0·0001) and transmitted more intensely (100 more transmission chains for a given population size [95% CI 41–171], p=0·0020) than other domestically acquired S sonnei. Isolates deriving from sexually transmitted shigellosis also had greater relative fitness and were 1·15 (95% credible interval 1·08–1·23) times as fit as isolates from high-risk travel transmission. The relative fitness of azithromycin resistance among pMSM was greater (1·71 relative growth [1·59–1·84]) than in either non-pMSM or high-risk travel demographics, and that declines of azithromycin fitness in sexual transmission networks coincided with changes in treatment policies for gonorrhoea. In a secondary analysis of 468 isolates, pathogen emergence was associated with resistance to ceftriaxone. Interpretation: Our study shows the distinct and intensifying sexual transmission of shigellosis, highlighting the urgent need to address sexually transmissible shigellosis as a distinct health threat. Traditional interventions for enteric diseases, such as handwashing and food hygiene practices, are not likely to affect sexual transmission of shigellosis, highlighting a crucial gap in public health management. The development of alternative interventions to address this public health threat is urgently needed. Furthermore, the unequivocal evidence of bystander resistance driven by treatment guidelines in a syndemic setting underscores the need to better manage antimicrobial stewardship across pathogens at a public health level. Funding: The UK Biotechnology and Biological Sciences Research Council, the UK Research and Innovation Medical Research Council, National Institute for Health and Care Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool, and the Eidgenössische Technische Hochschule Zürich Postdoctoral Fellowship Programme.