Genomic epidemiology of the first London outbreak of antimicrobial resistant sexually transmitted shigellosis

Abstract

Shigellosis is an intestinal infection caused by Shigella bacteria. Shigella cause an estimated ~200,000 global deaths annually. Antimicrobial resistant (AMR) shigellosis is a significant cause of morbidity in high-income nations, with both multidrug resistant (MDR) and extensively drug resistant (XDR) cases being increasingly reported in Australia, England, and the USA. Sexually transmissible shigellosis was first described in San Francisco, 1974, but it would be a further 30 years before its first description in England. In 2004, London experienced an outbreak of Shigella sonnei (S. sonnei) mediated sexually transmitted shigellosis, associated with men-who-have-sex-with-men (MSM). Since then, sexually transmissible shigellosis has become endemic in England, with a greater than two-fold increase in Shigella diagnoses within sexual health services from 2015 to 2019. Through genomic exploration of samples from the original 2004 outbreak (provided by Public Health England (PHE)), we identified that the 2004 London outbreak isolates clustered within the base of genotype 3.1, lineage III, a lineage which has since gone on to dominate the global epidemiology of S. sonnei. The isolates displayed early evidence of varying degrees of antimicrobial resistance to several drug classes: macrolides, tetracyclines, beta-lactams and sulphonamides. Reconstructing the chronological process of how shigellosis has arrived at its current position in AMR and transmissibility is critical. Further investigation is underway to link this outbreak with MSM-associated shigellosis outbreaks occurring in the early 2000s in other countries to establish whether this lineage globally disseminated; determine the timeframe for global connectivity of shigellosis; and examine the outbreak isolates for virulence determinants.