The natural history of the emergence of sexually transmissible shigellosis

Shigellosis is a gastrointestinal illness caused by bacteria belonging to one of four species of <i>Shigella</i>. Sexually transmissible (ST) shigellosis was first reported in 1974, but recently there has been a global increase in the transmission of extensively drug-resistant (XDR) strains. Here, we sought to characterise the natural history of ST shigellosis through literature review and genomic epidemiological analysis of early outbreaks. The literature review revealed a significant gap in reporting of ST shigellosis between the first report in 1974 and the early 2000s, after which reporting increased. To better understand this sustained emergence of ST shigellosis in the 21st century, we explored potential pathogen factors and linked these with changes in host populations. Specifically, we analysed the genomic epidemiology of preserved strains from outbreaks in both Berlin (2000-2002) and London (2004-2006). Both outbreaks were <i>Shigella sonnei</i> Genotype 3.1, an ancestral branch of the globally disseminated lineage III subtype, which is distinct from the currently globally dominant XDR forms (Genotypes 3.6.1.1.2 and 3.6.1.1) circulating in sexual transmission networks. We also describe the variable antimicrobial resistance, conserved colicin genes and differing virulence and plasmid profiles between the London and Berlin outbreaks. Finally, we conducted temporal reconstruction of Genotype 3.1 and found that the most recent common ancestor occurred in 1999 (95% highest posterior density 1997-2000), which is coincident with the introduction of highly active antiretroviral therapy (HAART) for human immunodeficiency virus. This suggests that changes associated with the introduction of HAART may have contributed to the re-emergence of ST shigellosis in the 21st century.