Shigellosis is a sexually transmissible enteric infection caused by Shigella bacteria. Between 2009 and 2014, Shigella flexneri (S. flexneri) 3a was the most dominant species and serotype of sexually transmissible shigellosis among men who have sex with men (MSM) in England, United Kingdom. Subsequently, S. flexneri 3a diagnoses declined to pre-epidemic levels. However, in 2020, despite SARS-CoV-2 restrictions, S. flexneri 3a re-emerged as the dominant species and serotype associated with sexual transmission. Through a combination of whole-genome-sequencing and epidemiological methods, our work aimed to elucidate the reason(s) for the re-emergence of S. flexneri 3a. The age and geographical distribution of cases in the 2009-2014 cohort compared to the 2018-2020 cohort is largely unchanged, with most cases among those aged 35 - 64 years, in London and the Southeast of England. Enhanced surveillance questionnaires (ESQ) were available for 37.9% (n = 67/177) of cases in 2019-2020, and 35.8% (n = 24/177) reported being hospitalised, with a median admission length of 2 days. The majority (n = 36/177, 53.7%) self-identified as a gay or bisexual man. Phylogenetic analysis showed that most strains driving the re-emergence had evolved from the 2009-2013 epidemic strains, although the antibiotic resistance (AMR) profiles had changed. The most recent isolates had lost blaTEM-1 and erm(B). We combined enhanced surveillance and genomic data to investigate correlations between disease severity, virulence, and AMR determinants. Our work demonstrates the importance of collaboration between genomic and population epidemiologists, to gain insight into emerging threats to public health and to predict and prevent gastrointestinal disease.
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