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

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          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.

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          Most cited references27

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          Is Open Access

          Hierarchical and Spatially Explicit Clustering of DNA Sequences with BAPS Software

          Phylogeographical analyses have become commonplace for a myriad of organisms with the advent of cheap DNA sequencing technologies. Bayesian model-based clustering is a powerful tool for detecting important patterns in such data and can be used to decipher even quite subtle signals of systematic differences in molecular variation. Here, we introduce two upgrades to the Bayesian Analysis of Population Structure (BAPS) software, which enable 1) spatially explicit modeling of variation in DNA sequences and 2) hierarchical clustering of DNA sequence data to reveal nested genetic population structures. We provide a direct interface to map the results from spatial clustering with Google Maps using the portal http://www.spatialepidemiology.net/ and illustrate this approach using sequence data from Borrelia burgdorferi. The usefulness of hierarchical clustering is demonstrated through an analysis of the metapopulation structure within a bacterial population experiencing a high level of local horizontal gene transfer. The tools that are introduced are freely available at http://www.helsinki.fi/bsg/software/BAPS/.
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            Shigellosis

            Shigellosis is a clinical syndrome caused by invasion of the epithelium lining the terminal ileum, colon, and rectum by Shigella species. Although infections occur globally, and in people of all ages, endemic infections among children aged 1-4 years living in low-income and middle-income settings constitute most of the disease burden. The versatile manifestations of these highly contagious organisms range from acute watery diarrhoea to fulminant dysentery characterised by frequent scant bloody stools with fever, prostration, and abdominal cramps. A broad array of uncommon, but often severe, intestinal and extraintestinal complications can occur. Despite marked reductions in mortality during the past three decades, there are roughly 164 000 annual deaths attributable to shigellosis. Intercontinental dissemination of multiresistant shigella strains, facilitated by travellers and men who have sex with men, has prompted new recommendations for antibiotic therapy. Awareness of disease burden and the emerging threats posed by shigella have accelerated interest in development of shigella vaccines, many of which are being tested in clinical trials.
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              Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe

              Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery 1,2 , spreading efficiently via low-dose fecal-oral transmission 3,4 . Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality 4-6 . Classical approaches have shown S. sonnei is genetically conserved and clonal 7 . We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage.
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                Author and article information

                Journal
                Clinical Infectious Diseases
                Oxford University Press (OUP)
                1058-4838
                1537-6591
                November 01 2019
                October 15 2019
                January 07 2019
                November 01 2019
                October 15 2019
                January 07 2019
                : 69
                : 9
                : 1535-1544
                Affiliations
                [1 ]Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne
                [2 ]National Centre for Epidemiology and Population Health, The Australian National University, Canberra
                [3 ]Victorian Department of Health and Human Services, Melbourne
                [4 ]Melbourne Bioinformatics Group, Victoria, Australia
                [5 ]Doherty Applied Microbial Genomics, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Australia
                [6 ]Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Australia
                [7 ]London School of Hygiene and Tropical Medicine, United Kingdom
                [8 ]Melbourne Sexual Health Centre, Alfred Health, Carlton
                [9 ]Central Clinical School, Monash University, Melbourne, Australia
                Article
                10.1093/cid/ciz005
                30615105
                5c074db3-a606-468e-9724-319916abcdc3
                © 2019

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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