Co-circulation of Multidrug-resistant Shigella Among Men Who Have Sex With Men in Australia

Abstract

Background In urban Australia, the burden of shigellosis is either in returning travelers from shigellosis-endemic regions or in men who have sex with men (MSM). Here, we combine genomic data with comprehensive epidemiological data on sexual exposure and travel to describe the spread of multidrug-resistant Shigella lineages. Methods A population-level study of all cultured Shigella isolates in the state of Victoria, Australia, was undertaken from 1 January 2016 through 31 March 2018. Antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analyses of 545 Shigella isolates were performed at the Microbiological Diagnostic Unit Public Health Laboratory. Risk factor data on travel and sexual exposure were collected through enhanced surveillance forms or by interviews. Results Rates of antimicrobial resistance were high, with 17.6% (95/541) and 50.6% (274/541) resistance to ciprofloxacin and azithromycin, respectively. There were strong associations between antimicrobial resistance, phylogeny, and epidemiology. Specifically, 2 major MSM-associated lineages were identified: a Shigellasonnei lineage (n = 159) and a Shigella flexneri 2a lineage (n = 105). Of concern, 147/159 (92.4%) of isolates within the S. sonnei MSM-associated lineage harbored mutations associated with reduced susceptibility to recommended oral antimicrobials: namely, azithromycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Long-read sequencing demonstrated global dissemination of multidrug-resistant plasmids across Shigella species and lineages, but predominantly associated with MSM isolates. Conclusions Our contemporary data highlight the ongoing public health threat posed by resistant Shigella, both in Australia and globally. Urgent multidisciplinary public health measures are required to interrupt transmission and prevent infection.

The importance of a multifactorial approach for (inter)national surveillance of Shigella spp. and entero-invasive Escherichia coli

“…These clusters also contained isolates from men that reported no sexual contact with other men or isolates from women. This could possibly be due to spillover to the non-MSM population, or (8,11). Our study confirmed this phenomenon for the Dutch situation, as 30% to 100% of patients infected with isolates within MSM-associated clusters reported also an HIV infection, and only three patients that reported HIV were infected with isolates outside the MSM clusters.…”

“…Additionally, vertically transferred chromosomal point mutations mainly conferring resistance to quinolones can be present (8,17). Multiple studies indicated that the presence of resistance genes or point mutations in whole genome sequences of E. coli and S. sonnei, accurately predicts phenotypic AMR (18)(19)(20)(21).…”

Persistent transmission of shigellosis in England is associated with a recently emerged multi-drug resistant strain ofShigella sonnei

“…Hierarchical single linkage clustering was performed on the pairwise SNP difference between all isolates at various distance thresholds (Δ250, Δ100, Δ50, Δ25, Δ10, Δ5, Δ0) [27]. Genome-derived serotyping and AMR-conferring genes and SNPs was performed using the GeneFinder tool (https://github.com/phe-bioinformatics/gene_finder) [21,28]. Resistance to streptomycin, tetracycline, the sulphonamides and trimethoprim in Shigella species is high, and trends have been consistent for many years [5,[15][16][17]28].…”

“…FASTQ reads from all sequences in this study can be found at the PHE Bioproject PRJNA315192. For international context, 110 S. sonnei sequences isolated from Australian MSMs, previously reported by Ingle et al (2019), were processed as above for phylogenetic comparison.…”

“…Within the S. sonnei population, Baker et al (2018) [16] defined four clades associated with transmission in GBMSM communities, all within lineage III the dominant extant lineage both in the UK and globally [19,20]. A two-year population-level study of all cultured Shigella isolates in the state of Victoria, Australia (2016-2018) identified 2 predominant MSM lineages circulating [21]; the S. flexneri 2a lineage described above and an MDR S. sonnei clade associated with reduced susceptibility to azithromycin, trimethoprim-sulfamethoxazole and ciprofloxacin.…”