Amee Manges

Urinary tract infections (UTIs) are one of the most common bacterial infections worldwide. Extra-intestinal pathogenic Escherichia coli (ExPEC) are responsible for more than 80% of UTIs. ExPEC have been isolated from the environment, food sources and companion animals. Once acquired from an external source, ExPEC asymptomatically colonize the intestinal tract, and act as an immediate reservoir for subsequent extra-intestinal infection. Despite considerable ExPEC diversity, only a few multi-locus sequence types (STs) cause the majority of infections. Our study examines the population structure and exposures associated with UTI caused by major ExPEC lineages. A total of 385 women with community-acquired UTI caused by E. coli across Canada were questioned about their diet, travel and other exposure history. Genome sequencing was used to determine both ST and genomic similarity. ST69, ST73, ST95, ST127 and ST131 were responsible for 54% of all UTIs. Seven UTI clusters were identified, but genomes from the ST95 and ST420 clusters exhibited fewer than 4 single nucleotide variations, suggesting recent transmission from a common source. The predominant STs were all associated with consumption of high-risk foods such as seafood and raw meat, and all STs, except for ST73, were associated with travel. These results suggest specific exposures exist for pandemic ExPEC lineages. Identifying the reservoirs of common, community-acquired ExPEC lineages will aid our understanding of the evolution, emergence, and dissemination of high-risk clones within the community setting.

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Background.Environmental enteric dysfunction (EED) is commonly defined as an acquired subclinicaldisorder of the small intestine, characterized by villous atrophy and crypt hyperplasia. EED hasbeen proposed to underlie stunted growth among children in developing countries. A collectionof biomarkers, organized into distinct domains, has been used to measure different aspects ofEED. Here, we examine whether these hypothesized relationships, among EED domains andbetween each domain and stunting, are supported by data from recent studies.Methodology.A systematic literature search was conducted using PubMed, MEDLINE, EMBASE, Web ofScience, and CINAHL between January 1, 2010 and April 20, 2017. Information on studyobjective, design, population, location, biomarkers, and results were recorded, as well asqualitative and quantitative definitions of EED. Biomarkers were organized into five EEDdomains, and the number of studies that support or do not support relationships among domainsand between each domain with stunting were summarized.Results.There was little evidence to support the pathway from intestinal permeability to microbialtranslocation and from microbial translocation to stunting, but stronger support existed for thelink between intestinal inflammation and systemic inflammation and for intestinal inflammationand stunting. There was conflicting evidence for the pathways from intestinal damage tointestinal permeability and intestinal damage to stunting.Conclusions.These results suggest that certain EED biomarkers may require reconsideration, particularlythose most difficult to measure, such as microbial translocation and intestinal permeability. Wediscuss several issues with currently used biomarkers and recommend further analysis ofpathogen-induced changes to the intestinal microbiota as a pathway leading to stunting.

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