Sexually transmissible Shigella sonnei spread over greater geographic distances and showed greater transmission intensity than other domestically acquired S. sonnei in England, according to a genomic epidemiology study published in The Lancet Infectious Diseases. Sexually transmissible shigellosis represents a distinct public health challenge that may warrant tailored prevention and antimicrobial stewardship strategies.
"This work raises an important gap in infectious disease management because traditional interventions recommended for enteric illnesses (eg, handwashing and food hygiene) are unlikely to impact sexual transmission pathways, so it is imperative that we urgently develop alternative interventions, such as effective vaccines, microbiological clearance pathways, and tailored treatment guidelines, in partnership with patient communities," wrote the study authors.
First author Julia E. Marshall, of the Department of Genetics at the University of Cambridge and the Department of Epidemiology of Microbial Diseases at Yale School of Public Health, and colleagues analyzed 3,514 S. sonnei isolates referred to the UK Health Security Agency's national surveillance system from 138 laboratories across 15 UK health regions from Sept. 20, 2004, through Feb. 28, 2020.
The researchers grouped cases as high-risk travel-associated, presumptive men who have sex with men (pMSM) or non-pMSM. The pMSM group included males aged 16 to 60 years without reported high-risk travel in the previous 28 days, defined as travel to Africa, Asia, or Latin America and the Caribbean. Non-pMSM included cases that did not meet the criteria for either pMSM or high-risk travel-associated infection.
Of the 3,514 sequenced isolates, 1,197 (34.1%) were classified as pMSM, 1,269 (36.1%) as non-pMSM and 1,048 (29.8%) as high-risk travel-associated. Resistance to at least one of three clinically important antimicrobials — ciprofloxacin, azithromycin or ceftriaxone — was detected in 69.4% of pMSM isolates, compared with 48.9% of high-risk travel-associated isolates and 39.6% of non-pMSM isolates.
The investigators found marked differences in geographic spread. Among genetically related isolates separated by no more than 2.5 years of evolutionary time, the mean geographic distance between pMSM isolates was 117.4 km (95% CI, 100.7-132.3), compared with 45.8 km (95% CI, 32.6-62.1) for non-pMSM isolates (P<.0001).
After accounting for population size, the researchers estimated that 100 additional transmission chains were circulating among pMSM compared with non-pMSM (95% CI, 41-171; P=.002). pMSM isolates also remained genetically distinct for up to 15 years, whereas non-pMSM isolates became broadly mixed after approximately 2.5 years.In addition, isolates associated with presumed sexual transmission had greater estimated relative fitness and were 1.15 times as fit as high-risk travel-associated isolates (95% credible interval, 1.08-1.23), suggesting sustained circulation and a transmission advantage within sexual networks.
Antimicrobial resistance also appeared to influence pathogen fitness differently across transmission groups. Before 2018, azithromycin resistance was associated with greater relative growth among pMSM isolates, at 1.71 (95% credible interval, 1.59-1.84), than among non-pMSM and high-risk travel-associated isolates. The estimated fitness advantage declined after UK gonorrhea treatment guidelines changed in 2018 to remove routine azithromycin-containing dual therapy. The temporal association supports what the researchers described as bystander resistance, in which antimicrobial use targeting one pathogen can select for resistance in another pathogen circulating within the same population.
In a secondary analysis of 468 isolates collected in England from 2016 through 2021, investigators examined emergence of an extensively drug-resistant S. sonnei clade, finding that its expansion was associated with acquisition of ceftriaxone resistance.
Conventional measures used to limit enteric infections, including handwashing and food hygiene, are unlikely to adequately address transmission through sexual contact. The researchers instead called for more tailored approaches, including targeted education, microbiological clearance pathways, vaccination and treatment guidance developed with affected communities. They also highlighted the need for antimicrobial stewardship strategies that consider interactions between pathogens treated within sexual health services.
Limitations included use of demographic and travel data as a proxy for sexual transmission, creating potential for misclassification, and use of laboratory rather than residential or transmission postcodes for geographic analyses. Travel history was missing or unknown for 1,795 cases (51.1%), whom investigators assumed had no recent high-risk travel. Sequencing before 2015 was also limited, and the primary analysis ended in February 2020 because the COVID-19 pandemic disrupted shigellosis transmission patterns.
The study was funded by the UK Biotechnology and Biological Sciences Research Council, 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 ETH Zürich Postdoctoral Fellowship Programme. Kate S. Baker, PhD, Noemie Lefrancq, PhD, and Lewis C.E. Mason, PhD, reported relevant grant funding. The remaining authors declared no competing interests.
