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Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales.

In April 2018, Public Health England was notified of cases of Shigella sonnei who had eaten food from three different catering outlets in England. The outbreaks were initially investigated as separate events, but whole-genome sequencing (WGS) showed they were caused by the same strain. The investigation included analyses of epidemiological data, the food chain and microbiological examination of food samples. WGS was used to determine the phylogenetic relatedness and antimicrobial resistance profile of the outbreak strain. Ultimately, 33 cases were linked to this outbreak; the majority had eaten food from seven outlets specialising in Indian or Middle Eastern cuisine. Five outlets were linked to two or more cases, all of which used fresh coriander although a shared supplier was not identified. An investigation at one of the venues recorded that 86% of cases reported eating dishes with coriander as an ingredient or garnish. Four cases were admitted to hospital and one had evidence of treatment failure with ciprofloxacin. Phylogenetic analysis showed that the outbreak strain was part of a wider multidrug-resistant clade associated with travel to Pakistan. Poor hygiene practices during cultivation, distribution or preparation of fresh produce are likely contributing factors.

Whole-genome sequencing has enhanced surveillance and facilitated detailed monitoring of the transmission of Shigella species in England. We undertook an epidemiological and phylogenetic analysis of isolates from all cases of shigellosis referred to Public Health England between 2015 and 2018 to explore recent strain characteristics and the transmission dynamics of Shigella species. Of the 4,950 confirmed cases of shigellosis identified during this period, the highest proportion of isolates was Shigella sonnei (54.4%), followed by S. flexneri (39.2%), S. boydii (4.1%), and S. dysenteriae (2.2%). Most cases were adults (82.9%) and male (59.5%), and 34.9% cases reported recent travel outside the United Kingdom. Throughout the study period, diagnoses of S. flexneri and S. sonnei infections were most common in men with no history of recent travel abroad. The species prevalence was not static, with cases of S. flexneri infection in men decreasing between 2015 and 2016 and the number of cases of S. sonnei infection increasing from 2017. Phylogenetic analysis showed this recent increase in S. sonnei infections was attributed to a novel clade that emerged from a Central Asia sublineage exhibiting resistance to ciprofloxacin and azithromycin. Despite changes in species prevalence, diagnoses of Shigella infections in England are persistently most common in adult males without a reported travel history, consistent with sexual transmission among men who have sex with men. The trend toward increasing rates of ciprofloxacin resistance in S. sonnei , in addition to plasmid-mediated azithromycin resistance, is of significant public health concern with respect to the transmission of multidrug-resistant gastrointestinal pathogens and the risk of treatment failures., (© Crown copyright 2020.)

In December 2013, Public Health England (PHE) observed an increase in the number of cases of Shigella sonnei linked to the Orthodox Jewish Community (OJC). Ultimately, 52 cases of S. sonnei phage type (PT) P and PT7 were notified between November 2013 and July 2014. Whole-genome sequencing (WGS) was performed on a HiSeq 2500 platform (Illumina) on isolates of S. sonnei submitted to PHE during the investigation. Quality trimmed sequence reads were mapped to a reference genome using BWA-MEM, and single-nucleotide polymorphisms (SNPs) were identified using GATK2. Analysis of the core genome SNP positions (>90 % consensus, minimum depth 10×, MQ≥30) revealed that isolates linked to the outbreak could be categorized as members of distinct monophyletic clusters (MPCs) representing concurrent regional outbreaks occurring in the OJCs across the United Kingdom. A dated phylogeny predicted the date of the most recent common ancestor of the MPCs to be approximately 3.1 years previously [95 % highest posterior density (HPD), 2.4-3.4]. Isolates of S. sonnei from cases from the OJCs in Israel included in the phylogeny, branched from nodes basal to the UK OJC outbreak clusters, indicating they were ancestral to the UK OJC isolates, and that the UK isolates represented multiple importations of S. sonnei into the UK population from Israel. The level of discrimination exhibited by WGS facilitated the identification of clusters of isolates within the closely related bacterial populations circulating in the OJC that may be linked to a unique point sources or transmission routes, thus enabling a more appropriate public health response and targeted interventions.

Objectives: Phenotypic and genotypic methods for the detection of antimicrobial resistance (AMR) in Shigella sonnei in England and Wales were compared and evaluated., Methods: WGS data from 341 isolates of S. sonnei isolated between June 2015 and January 2016 were mapped to genes known to be associated with phenotypic AMR. Antimicrobial susceptibility testing was performed on all viable isolates (n = 335)., Results: Fifteen of 335 isolates had a discrepancy between phenotypic and genotypic testing for 1 of the 10 antimicrobial classes tested, equating to 15 (0.45%) discordant results out of a possible 3350 isolate/antimicrobial combinations. All 15 mismatched results were genotypically resistant but phenotypically susceptible. Eleven of the 15 discrepancies were observed in streptomycin resistance profiles. The most common resistance profile was trimethoprim, sulphonamides, tetracyclines and streptomycin, occurring in 97 (28.4%) isolates. Resistances to ciprofloxacin and the third-generation cephalosporins, not detected in England and Wales prior to 2002, were identified in 18.2% and 12% of isolates, respectively. Three hundred and four (89.1%) isolates were MDR. There was no significant association between any of the AMR determinants tested and recent foreign travel in male or female cases. The number of isolates of S. sonnei harbouring blaTEM-1 and ermB/mphA was significantly higher in men who reported no recent travel outside the UK., Conclusions: The use of WGS for routine public health surveillance is a reliable method for rapid detection of emerging AMR in isolates of S. sonnei., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In England in 2015, Shigella sonnei isolates from men who have sex with men produced extended-spectrum β-lactamases and exhibited macrolide resistance. Whole-genome sequencing showed a close relationship among the isolates, which harbored a plasmid that was previously identified in a shigellosis outbreak among this population but has acquired a mobile element.

Since 1983 the incidence of resistance to ampicillin in Shigella dysenteriae, Sh. flexneri, and Sh. boydii infections in England and Wales has increased from 42% to 65% and the incidence of resistance to trimethoprim, from 6% to 64%. Furthermore, of 1524 strains received in 1995-1996, 46% were resistant to both of these antimicrobials. For Sh. sonnei almost 50% of isolates were resistant to ampicillin or trimethoprim and 15% were resistant to both of these antimicrobials. These results demonstrate that if antibiotic therapy had been indicated for infections with Sh. dysenteriae, Sh. flexneri, and Sh. boydii, then treatment with either ampicillin or trimethoprim may have been ineffective in almost 50% of cases and for Sh. sonnei, in 15% of cases. It is concluded that if it is necessary to commence treatment before the results of laboratory-based sensitivity tests are available, the best options would be to use nalidixic acid for children and a fluoroquinolone antibiotic such as ciprofloxacin or ofloxacin, for adults.