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 Shigella . Sexually transmissible shigellosis was first reported in 1974, but recently there has been a global increase in the transmission of extensively drug-resistant strains. Here, we sought to characterise the natural history of sexually transmissible shigellosis through literature review and genomic epidemiological analysis of early outbreaks. The literature review revealed a significant gap in reporting of sexually transmissible shigellosis between the first report in 1974 and the early 2000s after which reporting increased. To better understand this sustained emergence of sexually transmissible shigellosis in the 21 ^st 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 S. sonnei Genotype 3.1, an ancestral branch of the globally disseminated Lineage III subtype, which is distinct from the currently extensively drug-resistant 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% HPD 1998 - 2000) which is coincident with the introduction of highly active antiretroviral therapy (HAART) for HIV. This suggests that changes associated with the introduction of HAART likely contributed to the re-emergence of sexually transmissible shigellosis in the 21 ^st Century.