Publications by authors named "Claire Jenkins"

140 Publications

Acquisition and loss of CTX-M plasmids in species associated with MSM transmission in the UK.

Microb Genom 2021 Aug;7(8)

University of Bath, Claverton Down Campus, Bath, UK.

Shigellosis in men who have sex with men (MSM) is caused by multidrug resistant Shigellae, exhibiting resistance to antimicrobials including azithromycin, ciprofloxacin and more recently the third-generation cephalosporins. We sequenced four -positive MSM isolates (2018-20) using Oxford Nanopore Technologies; three (identified as two MSM clade 2, one MSM clade 5) and one 3a, to explore AMR context. All isolates harboured Tn7/Int2 chromosomal integrons, whereas 3a contained the Resistance Locus. All strains harboured IncFII pKSR100-like plasmids (67-83kbp); where present was located on these plasmids flanked by IS and IS, however was lost in 3a during storage between Illumina and Nanopore sequencing. IncFII AMR regions were mosaic and likely reorganised by IS; three of the four plasmids contained azithromycin-resistance genes ) and ) and one harboured the pKSR100 integron. Additionally, all isolates possessed a large IncB/O/K/Z plasmid, two of which carried and ). Monitoring the transmission of mobile genetic elements with co-located AMR determinants is necessary to inform empirical treatment guidance and clinical management of MSM-associated shigellosis.
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http://dx.doi.org/10.1099/mgen.0.000644DOI Listing
August 2021

Subjective and objective sleep in young people with borderline personality disorder features.

J Sleep Res 2021 Aug 19:e13463. Epub 2021 Aug 19.

Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, Victoria, Australia.

Characterising sleep in young people (aged 15-25 years) with borderline personality disorder (BPD) features is crucial given the association between BPD features and sleep disturbance, negative consequences of poor sleep, and normative developmental sleep changes that occur in this age group. The present study aimed to characterise the sleep profile of young people with BPD to determine whether this profile is non-normative and specific to BPD. Participants were 96 young people (40 with BPD features, 38 healthy individuals, and 18 young people seeking help for mental health difficulties without BPD). Sleep was measured subjectively (self-report questionnaires) and objectively (10 days of actigraphy). Young people with BPD features reported poorer subjective sleep quality, greater insomnia symptoms and later chronotype than same-age healthy and clinical comparison groups. Young people with BPD features also displayed irregular sleep timing, later rise times, greater time in bed and longer sleep durations than healthy young people. Those with BPD features had superior sleep quality (greater sleep efficiency, less wake after sleep onset) and longer sleep durations than the clinical comparison group. Sleep profiles were similar across young people with BPD features with and without co-occurring depression. Overall, the findings revealed a subjective-objective sleep discrepancy and suggest that sleep-improvement interventions might be beneficial to improve subjective sleep in young people with BPD features.
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http://dx.doi.org/10.1111/jsr.13463DOI Listing
August 2021

Phylogenomics and antimicrobial resistance of Typhi and Paratyphi A, B and C in England, 2016-2019.

Microb Genom 2021 Aug;7(8)

Gastrointestinal Bacteria Reference Unit, National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.

The emergence of antimicrobial resistance (AMR) to first- and second-line treatment regimens of enteric fever is a global public-health problem, and routine genomic surveillance to inform clinical and public-health management guidance is essential. Here, we present the prospective analysis of genomic data to monitor trends in incidence, AMR and travel, and assess hierarchical clustering (HierCC) methodology of 1742 isolates of typhoidal salmonellae. Trend analysis of Typhi and . Paratyphi A cases per year increased 48 and 17.3%, respectively, between 2016 and 2019 in England, mainly associated with travel to South Asia. . Paratyphi B cases have remained stable and are mainly associated with travel to the Middle East and South America. There has been an increase in the number of . Typhi exhibiting a multidrug-resistant (MDR) profile and the emergence of extensively drug resistant (XDR) profiles. HierCC was a robust method to categorize clonal groups into clades and clusters associated with travel and AMR profiles. The majority of cases that had XDR . Typhi reported recent travel to Pakistan (94 %) and belonged to a subpopulation of the 4.3.1 (H58) clone (HC5_1452). The phenotypic and genotypic AMR results showed high concordance for . Typhi and . Paratyphi A, B and C, with 99.99 % concordance and only three (0.01 %) discordant results out of a possible 23 178 isolate/antibiotic combinations. Genomic surveillance of enteric fever has shown the recent emergence and increase of MDR and XDR . Typhi strains, resulting in a review of clinical guidelines to improve management of imported infections.
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http://dx.doi.org/10.1099/mgen.0.000633DOI Listing
August 2021

Emergence of Multidrug-Resistant Producing CTX-M, MCR-1, and FosA in Retail Food From Egypt.

Front Cell Infect Microbiol 2021 13;11:681588. Epub 2021 Jul 13.

Bacterial Epidemiology and Antimicrobial Resistance Research Unit, U.S. National Poultry Research Center, U.S. Department of Agriculture, Agricultural Research Service (USDA-ARS), Athens, GA, United States.

In this study, multidrug-resistant (MDR) isolates from retail food and humans assigned into similar Multilocus Sequence Types (MLST) were analyzed using whole genome sequencing (WGS). analysis of assembled sequences revealed the existence of multiple resistance genes among the examined isolates. Of the six CTX-M-producing isolates from retail food, was the prevalent variant identified (83.3%, 5/6). Two plasmid-mediated fosfomycin resistance genes, A3, and A4, were detected from retail food isolates (one each from chicken and beef), where A4 was identified in the chicken isolate 82CH that also carried the colistin resistance gene -1. The and A genes in retail food isolates were located adjacent to insertion sequences IS and IS, respectively. Sequence analysis of the reconstructed plasmid (p82CH) showed 96-97% identity to -carrying IncI2 plasmids previously identified in human and food isolates from Egypt. Hierarchical clustering of core genome MLST (HierCC) revealed clustering of chicken isolate 82CH, co-harboring and A4 genes, with a chicken isolate from China at the HC200 level (≤200 core genome allelic differences). As co-harboring and A4 genes has only been recently reported, this study shows rapid spread of this genotype that shares similar genetic structures with regional and international lineages originating from both humans and food animals. Adopting WGS-based surveillance system is warranted to facilitate monitoring the international spread of MDR pathogens.
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http://dx.doi.org/10.3389/fcimb.2021.681588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315045PMC
August 2021

The emerging importance of Shiga toxin-producing other than serogroup O157 in England.

J Med Microbiol 2021 Jul;70(7)

National Infection Service, Public Health England, London, UK.

Shiga toxin-producing (STEC) can cause severe disease and large outbreaks. In England, the incidence and clinical significance of STEC serogroups other than O157 (non-O157) is unknown due to a testing bias for detection of STEC O157. Since 2013, the implementation of PCR to detect all STEC serogroups by an increasing number of diagnostic laboratories has led to an increase in the detection of non-O157 STEC. Due to a bias in testing methodologies to select for STEC serogroup O157 in frontline diagnostic laboratories in most countries, very little surveillance data have been previously generated on non-O157 STEC. Five years (2014-2018) of STEC national surveillance data were extracted and descriptive analysis undertaken to assess disease severity of non-O157 STEC strains. Data from 1 January 2014 to 31 December 2018 were extracted from the National Enhanced Surveillance System for STEC and analysed. The implementation of Gastrointestinal Polymerase Chain Reaction (GI-PCR) has resulted in a four-fold increase in the detection of non-O157 STEC cases between 2014 and 2018. There were 2579 cases infected with 97 different non-O157 serogroups. The gender distribution was similar amongst STEC O157 and non-O157 STEC cases with 57 and 56 % of cases being female respectively, but a significantly higher proportion of cases ( <0.001) under 5 years of age was observed among STEC O157 (22 %) cases compared to non-O157 STEC (14 %). The most common non-O157 serogroups were O26 (16 %), O146 (11 %), O91 (10 %), O128 (7 %), O103 (5 %) and O117 (3 %). Overall, rates of bloody diarrhoea were highest in O26 (44 %) and O103 (48 %) cases and lowest in STEC O117 cases (17 %). Strains harbouring Shiga toxin caused the highest proportion of diarrhoea (93 %) and caused the same level of bloody diarrhoea as (39 %). However, caused the highest proportion of vomiting (46 %), hospitalisation (49 %) and considerably more HUS (29 %) than other profiles. The implementation of PCR targeting at diagnostic laboratories has shown that non-O157 STEC, most notably STEC O26, are an emerging risk to public health.
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http://dx.doi.org/10.1099/jmm.0.001375DOI Listing
July 2021

Sleep in Young People with Features of Borderline Personality Disorder: A Scoping Review.

J Pers Disord 2021 Jun 14:1-19. Epub 2021 Jun 14.

Orygen, Parkville, Victoria, Australia.

Sleep disturbance is commonly reported in young people with features of borderline personality disorder (BPD). Examining sleep quality and sleep-wake patterns in young people with features of BPD is essential to inform the development of sleep-improvement interventions. A scoping review was conducted according to the Joanna Briggs Institute methodology. The objectives were to map the literature regarding sleep in young people with features of BPD, highlight areas for further investigation, and provide methodological recommendations for future research. Seven data sets were included in the review. Young people with features of BPD had poorer objective and subjective sleep quality, disturbed sleep architecture (particularly rapid-eye-movement sleep), an increased vulnerability to delayed sleep phase syndrome, and more nightmares and dream anxiety, compared with healthy individuals. Future research should use both objective and subjective sleep measures, include clinical comparison groups, and focus specifically on young people with BPD.
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http://dx.doi.org/10.1521/pedi_2021_35_525DOI Listing
June 2021

Evidence of on-going transmission of Shiga toxin-producing O157:H7 following a foodborne outbreak.

Epidemiol Infect 2021 06 7;149:e147. Epub 2021 Jun 7.

National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5EQ, UK.

In August 2019, public health surveillance systems in Scotland and England identified seven, geographically dispersed cases infected with the same strain (defined as isolates that fell within the same five single nucleotide polymorphism single linage cluster) of Shiga toxin-producing Escherichia coli O157:H7. Epidemiological analysis of enhanced surveillance questionnaire data identified handling raw beef and shopping from the same national retailer (retailer A) as the common exposure. Concurrently, a microbiological survey of minced beef at retail identified the same strain in a sample of minced beef sold by retailer A, providing microbiological evidence of the link. Between September and November 2019, a further four primary and two secondary cases infected with the same strain were identified; two cases developed haemolytic uraemic syndrome. None of the four primary cases reported consumption of beef from retailer A and the transmission route of these subsequent cases was not identified, although all four primary cases visited the same petting farm. Generally, outbreaks of STEC O157:H7 in the UK appear to be distinct, short-lived events; however, on-going transmission linked to contaminated food, animals or environmental exposures and person-to-person contact do occur. Although outbreaks of STEC caused by contaminated fresh produce are increasingly common, undercooked meat products remain a risk of infection.
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http://dx.doi.org/10.1017/S0950268821001278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251666PMC
June 2021

Comparing GENEActiv against Actiwatch-2 over Seven Nights Using a Common Sleep Scoring Algorithm and Device-Specific Wake Thresholds.

Behav Sleep Med 2021 Jun 5:1-11. Epub 2021 Jun 5.

Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, Australia.

Demonstrating inter-device reliability is essential to use devices interchangeably, and accurately integrate, interpret, or compare data from different actigraphs. Despite this, there is a paucity of comparative literature over a timeframe exceeding one night. The aims of this study were to determine an optimal wake threshold for GENEActiv and to evaluate the concordance between Actiwatch-2 and GENEActiv using a common algorithm (Phillips Respironics). Data were collected from 33 individuals (20 female) aged 20-35 years (= 25.33, 4.69) across a total 213 nights. Participants wore both devices simultaneously and continuously for seven days. The sleep parameters of interest were: total sleep time, sleep efficiency, sleep onset latency, and wake after sleep onset. Exploratory analyses of sensitivity, specificity, overall accuracy, mean bias, and paired samples t-tests indicated an optimal wake threshold of 115 for GENEActiv, compared with Actiwatch-2 at the 40 (medium, default) threshold. Using these thresholds, sensitivity, and overall accuracy of GENEActiv were both good (86% and 78%, respectively), however specificity was relatively low (40%). There were no significant inter-device differences for any sleep parameters, and all absolute mean biases were small. Overall, the findings from this study provide the first empirical evidence to support the reliability of GENEActiv against Actiwatch-2 over multiple nights using a common algorithm with device-specific wake thresholds.
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http://dx.doi.org/10.1080/15402002.2021.1924175DOI Listing
June 2021

Beyond Strong Enforcement: Understanding the Factors Related to Retailer Compliance with Tobacco 21.

Nicotine Tob Res 2021 May 13. Epub 2021 May 13.

College of Public Health, The Ohio State University, Columbus, OH, 43210, USA.

Introduction: Tobacco 21 (T21), which sets the minimum legal sales age for tobacco to age 21, is now a national law in the U.S. Although T21 is expected to help curb youth tobacco use, its impact may be dampened due to poor retailer compliance. Even within environments where enforcement is strong (i.e., compliance checks are conducted with tough sanctions for violations), compliance might vary due to other factors.

Methods: Three studies were conducted in Columbus, OH, where T21 became strongly enforced in 2018. These studies examined how retailer compliance related to features of the neighborhood in which a retailer was located (Study 1), features of the retailer (Study 2), and features of the retail cashier (Study 3).

Results: Study 1 found that, after controlling for race- and age-based factors, retailers located in high (vs. low) poverty neighborhoods had a lower likelihood of conducting ID checks. Study 2 found that ID checks were related to whether retailers displayed signage about T21, as required by the city law. Study 3 found that, among cashiers, T21 awareness (which was high) and perceptions about T21 (which were moderate) were not generally related to their retailer's compliance; having (vs. not having) scanners for ID checks was related to a higher likelihood of compliance.

Conclusions: These studies emphasize the many, multi-level factors influencing T21 outcomes. Findings also indicate the potential for T21 to widen disparities in tobacco use, indicating the need for strategies to equitably improve T21 compliance.
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http://dx.doi.org/10.1093/ntr/ntab093DOI Listing
May 2021

Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei.

Nat Commun 2021 05 11;12(1):2684. Epub 2021 May 11.

Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia.

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.
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http://dx.doi.org/10.1038/s41467-021-22700-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113504PMC
May 2021

A cluster of Shiga Toxin-producing O157:H7 highlights raw pet food as an emerging potential source of infection in humans.

Epidemiol Infect 2021 05 6;149:e124. Epub 2021 May 6.

National Infection Service, Public Health England, 61 Colindale Avenue, LondonNW9 5HT, UK.

In August 2017, a cluster of four persons infected with genetically related strains of Shiga toxin-producing Escherichia coli (STEC) O157:H7 was identified. These strains possessed the Shiga toxin (stx) subtype stx2a, a toxin type known to be associated with severe clinical outcome. One person died after developing haemolytic uraemic syndrome. Interviews with cases revealed that three of the cases had been exposed to dogs fed on a raw meat-based diet (RMBD), specifically tripe. In two cases, the tripe had been purchased from the same supplier. Sampling and microbiological screening of raw pet food was undertaken and indicated the presence of STEC in the products. STEC was isolated from one sample of raw tripe but was different from the strain causing illness in humans. Nevertheless, the detection of STEC in the tripe provided evidence that raw pet food was a potential source of human STEC infection during this outbreak. This adds to the evidence of raw pet food as a risk factor for zoonotic transmission of gastrointestinal pathogens, which is widely accepted for Salmonella, Listeria and Campylobacter spp. Feeding RMBD to companion animals has recently increased in popularity due to the belief that they provide health benefits to animals. Although still rare, an increase in STEC cases reporting exposure to RMBDs was detected in 2017. There has also been an increased frequency of raw pet food incidents in 2017, suggesting an increasing trend in potential risk to humans from raw pet food. Recommendations to reduce the risk of infection included improved awareness of risk and promotion of good hygiene practices among the public when handling raw pet food.
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http://dx.doi.org/10.1017/S0950268821001072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161292PMC
May 2021

Accessory Genome Dynamics and Structural Variation of from Persistent Infections.

mBio 2021 04 27;12(2). Epub 2021 Apr 27.

Clinical Infection, Microbiology and Immunity, Institute of Infection, Veterinary and Ecological Sciences, The University of Liverpool, Liverpool, United Kingdom

Shigellosis is a diarrheal disease caused mainly by and Infection is thought to be largely self-limiting, with short- to medium-term and serotype-specific immunity provided following clearance. However, cases of men who have sex with men (MSM)-associated shigellosis have been reported where of the same serotype were serially sampled from individuals between 1 and 1,862 days apart, possibly due to persistent carriage or reinfection with the same serotype. Here, we investigate the accessory genome dynamics of MSM-associated and isolates serially sampled from individual patients at various days apart to shed light on the adaptation of these important pathogens during infection. We find that pairs likely associated with persistent infection/carriage and with a smaller single nucleotide polymorphism (SNP) distance, demonstrated significantly less variation in accessory genome content than pairs likely associated with reinfection, and with a greater SNP distance. We observed antimicrobial resistance acquisition during carriage, including the gain of an extended-spectrum beta-lactamase gene during carriage. Finally, we explored large chromosomal structural variations and rearrangements in seven (five chronic and two reinfection associated) pairs of 3a isolates from an MSM-associated epidemic sublineage, which revealed variations at several common regions across isolate pairs, mediated by insertion sequence elements and comprising a distinct predicted functional profile. This study provides insight on the variation of accessory genome dynamics and large structural genomic changes in during persistent infection/carriage. In addition, we have also created a complete reference genome and biobanked isolate of the globally important pathogen, 3a. spp. are Gram-negative bacteria that are the etiological agent of shigellosis, the second most common cause of diarrheal illness among children under the age of five in low-income countries. In high-income countries, shigellosis is also a sexually transmissible disease among men who have sex with men. Within the latter setting, we have captured prolonged and/or recurrent infection with shigellae of the same serotype, challenging the belief that infection is short lived and providing an early opportunity to study the evolution of the pathogen over the course of infection. Using this recently emerged transmission scenario, we comprehensively characterize the genomic changes that occur over the course of individual infection with and uncover a distinct functional profile of variable genomic regions, findings that have relevance for other .
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http://dx.doi.org/10.1128/mBio.00254-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092226PMC
April 2021

Outbreak of Shiga toxin-producing Escherichia coli O157 linked with consumption of a fast-food product containing imported cucumbers, United Kingdom, August 2020.

Int J Infect Dis 2021 Apr 22. Epub 2021 Apr 22.

Field Service, Public Health England, Birmingham, UK; Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, Liverpool, UK.

Background: In August 2020, an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157:H7 occurred in the United Kingdom. Whole genome sequencing revealed that these cases formed a genetically distinct cluster.

Methods: Hypotheses generated from case interviews were tested in analytical studies, and results informed environmental sampling and food chain analysis. A case-case study used non-outbreak 'comparison' STEC cases; a case-control study used a market research panel to recruit controls.

Results: A total of 36 cases were identified; all cases reported symptom onset between August 3 and August 16, 2020. The majority of cases (83%) resided in the Midlands region of England and in Wales. A high proportion of cases reported eating out, with one fast-food restaurant chain mentioned by 64% (n = 23) of cases. Both the case-case study (adjusted odds ratio (aOR) 31.8, 95% confidence interval (CI) 1.6-624.9) and the case-control study (aOR 9.19, 95% CI 1.0-82.8) revealed statistically significant results, showing that the consumption of a specific fast-food product was independently associated with infection.

Conclusions: Consumption of a specific fast-food product was a likely cause of this outbreak. The only ingredient specific to the product was cucumbers. The supply of cucumbers was immediately halted, and no further cases have been identified.
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http://dx.doi.org/10.1016/j.ijid.2021.04.001DOI Listing
April 2021

Phylogenetic context of Shiga toxin-producing serotype O26:H11 in England.

Microb Genom 2019 Sep;7(6)

National Infection Service, Public Health England, London, NW9 5EQ, UK.

The increasing use of PCR for the detection of gastrointestinal pathogens in hospital laboratories in England has improved the detection of Shiga toxin-producing (STEC), and the diagnosis of haemolytic uraemic syndrome (HUS). We aimed to analyse the microbiological characteristics and phylogenetic relationships of STEC O26:H11, clonal complex (CC) 29, in England to inform surveillance, and to assess the threat to public health. There were 502 STEC belonging to CC29 isolated between 2014 and 2019, of which 416 were from individual cases. The majority of isolates belonged to one of three major sequence types (STs), ST16 (=37), ST21 (=350) and ST29 (=24). ST16 and ST29 were mainly isolated from cases reporting recent travel abroad. Within ST21, there were three main clades associated with domestic acquisition. All three domestic clades had Shiga toxin subtype gene () profiles associated with causing severe clinical outcomes including STEC-HUS, specifically either , or . Isolates from the same patient, same household or same outbreak with an established source for the most part fell within 5-SNP single linkage clusters. There were 19 5-SNP community clusters, of which six were travel-associated and one was an outbreak of 16 cases caused by the consumption of contaminated salad leaves. Of the remaining 12 clusters, 9/12 were either temporally or geographically related or both. Exposure to foodborne STEC O26:H11 ST21 capable of causing severe clinical outcomes, including STEC-HUS, is an emerging risk to public health in England. The lack of comprehensive surveillance of this STEC serotype is a concern, and there is a need to expand the implementation of methods capable of detecting STEC in local hospital settings.
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http://dx.doi.org/10.1099/mgen.0.000551DOI Listing
September 2019

Phylogenetic structure of Shiga toxin-producing O157:H7 from sub-lineage to SNPs.

Microb Genom 2021 03 15;7(3). Epub 2021 Mar 15.

National Infection Services, Public Health England, 61 Colindale Avenue, London, NW9 5EQ, UK.

Sequence similarity of pathogen genomes can infer the relatedness between isolates as the fewer genetic differences identified between pairs of isolates, the less time since divergence from a common ancestor. Clustering based on hierarchical single linkage clustering of pairwise SNP distances has been employed to detect and investigate outbreaks. Here, we evaluated the evidence-base for the interpretation of phylogenetic clusters of Shiga toxin-producing (STEC) O157:H7. Whole genome sequences of 1193 isolates of STEC O157:H7 submitted to Public Health England between July 2015 and December 2016 were mapped to the Sakai reference strain. Hierarchical single linkage clustering was performed on the pairwise SNP difference between all isolates at descending distance thresholds. Cases with known epidemiological links fell within 5-SNP single linkage clusters. Five-SNP single linkage community clusters where an epidemiological link was not identified were more likely to be temporally and/or geographically related than sporadic cases. Ten-SNP single linkage clusters occurred infrequently and were challenging to investigate as cases were few, and temporally and/or geographically dispersed. A single linkage cluster threshold of 5-SNPs has utility for the detection of outbreaks linked to both persistent and point sources. Deeper phylogenetic analysis revealed that the distinction between domestic UK and imported isolates could be inferred at the sub-lineage level. Cases associated with domestically acquired infection that fall within clusters that are predominantly travel associated are likely to be caused by contaminated imported food.
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http://dx.doi.org/10.1099/mgen.0.000544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190602PMC
March 2021

ESBL-producing strains isolated from imported cases of enteric fever in England and Wales reveal multiple chromosomal integrations of blaCTX-M-15 in XDR Salmonella Typhi.

J Antimicrob Chemother 2021 05;76(6):1459-1466

Gastrointestinal Pathogens Department, National Infection Service, Public Health England, London, UK.

Background: There are approximately 300 cases of enteric fever reported annually from England and Wales; most are imported infections. Clinical management of enteric fever remains a challenge with the emergence of ESBL-producing strains, especially XDR Salmonella Typhi from Sindh, Pakistan.

Methods: All strains of S. Typhi and Salmonella Paratyphi A isolated from cases presenting with symptoms of enteric fever in England and Wales, between 1 April 2014 and 31 March 2020, were characterized using WGS. Antibiotic susceptibility testing was performed using an agar dilution method.

Results: ESBL strains contributed to 69 cases of enteric fever (S. Typhi n = 68, S. Paratyphi A n = 1); 68 were imported (Pakistan n = 64, Iraq n = 2, Bangladesh n = 1 and India n = 1). Ages ranged from 1 to 56 years, 36/69 (52%) were children, 52% were female and the duration of hospital stay ranged from 1 to 23 days. The ESBL phenotype was conferred by the presence of blaCTX-M-15 (S. Typhi n = 67 and S. Paratyphi A n = 1) or blaCTX-M-55 (S. Typhi n = 1). An IncY plasmid harbouring blaCTX-M-15 and qnr was detected in 56 strains from Pakistan. The IncY plasmid was absent in the remaining strains and there was evidence of a 4 kb ISEcpl-blaCTX-M-15-tnp gene cassette insertion into the chromosome at one of three integration points.

Conclusions: Chromosomal integration of blaCTX-M-15 within the XDR Sindh strains may lead to the maintenance of resistance in the absence of antibiotic selection pressure. Empirical treatment of cases of complicated enteric fever returning from Pakistan will henceforth have to include a carbapenem.
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http://dx.doi.org/10.1093/jac/dkab049DOI Listing
May 2021

Analysis of a small outbreak of Shiga toxin-producing O157:H7 using long-read sequencing.

Microb Genom 2021 03 8;7(3). Epub 2021 Mar 8.

Division of Infection and Immunity, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, EH25 9RG, UK.

Compared to short-read sequencing data, long-read sequencing facilitates single contiguous assemblies and characterization of the prophage region of the genome. Here, we describe our methodological approach to using Oxford Nanopore Technology (ONT) sequencing data to quantify genetic relatedness and to look for microevolutionary events in the core and accessory genomes to assess the within-outbreak variation of four genetically and epidemiologically linked isolates. Analysis of both Illumina and ONT sequencing data detected one SNP between the four sequences of the outbreak isolates. The variant calling procedure highlighted the importance of masking homologous sequences in the reference genome regardless of the sequencing technology used. Variant calling also highlighted the systemic errors in ONT base-calling and ambiguous mapping of Illumina reads that results in variations in the genetic distance when comparing one technology to the other. The prophage component of the outbreak strain was analysed, and nine of the 16 prophages showed some similarity to the prophage in the Sakai reference genome, including the -encoding phage. Prophage comparison between the outbreak isolates identified minor genome rearrangements in one of the isolates, including an inversion and a deletion event. The ability to characterize the accessory genome in this way is the first step to understanding the significance of these microevolutionary events and their impact on the evolutionary history, virulence and potentially the likely source and transmission of this zoonotic, foodborne pathogen.
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http://dx.doi.org/10.1099/mgen.0.000545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190617PMC
March 2021

Utility of whole-genome sequencing during an investigation of multiple foodborne outbreaks of .

Epidemiol Infect 2021 03 1;149:e71. Epub 2021 Mar 1.

National Infection Service, Public Health England, London, UK.

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.
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http://dx.doi.org/10.1017/S0950268821000509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060841PMC
March 2021

A Shiga Toxin-Encoding Prophage Recombination Event Confounds the Phylogenetic Relationship Between Two Isolates of O157:H7 From the Same Patient.

Front Microbiol 2020 23;11:588769. Epub 2020 Oct 23.

National Infection Service, Public Health England, London, United Kingdom.

We compared genomes from multiple isolations of Shiga toxin-producing (STEC) O157:H7 from the same patient, in cases notified to Public Health England (PHE) between 2015 and 2019. There were 261 cases where multiple isolates were sequenced from the same patient comprising 589 isolates. Serial isolates from the same patient fell within five single nucleotide polymorphisms (SNPs) of each other for 260/261 (99.6%) of the cases, indicating that there was little evidence of within host variation. The investigation into the 13 SNP discrepancy between one isolate pair revealed the cause to be a recombination event within a -encoding prophage resulting in the insertion/deletion of a fragment of the genome. This 50 kbp prophage fragment was homologous to a prophage in the reference genome, and the short reads from the isolate that had the 50 kbp fragment, mapped unambiguously to this region. The discrepant variants in the isolate without the 50 kbp fragment were attributed to ambiguous mapping of the short reads from other prophage regions to the 50 kbp fragment in the reference genome. Identification of such recombination events in this dataset appeared to be rare, most likely because the majority of prophage regions in the Sakai reference genome are masked during the analysis. Identification of SNPs under neutral selection, and masking recombination events, is a requirement for phylogenetic analysis used for public health surveillance, and for the detection of point source outbreaks. However, assaying the accessory genome by combining the use of short and long read technologies for public health surveillance may provide insight into how recombination events impact on the evolutionary course of STEC O157:H7.
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http://dx.doi.org/10.3389/fmicb.2020.588769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645076PMC
October 2020

Analysis Shiga Toxin-Encoding Bacteriophage in a Rare Strain of Shiga Toxin-Producing O157:H7 .

Front Microbiol 2020 21;11:577658. Epub 2020 Oct 21.

National Infection Service, Public Health England, London, United Kingdom.

In December 2015, six cases of Shiga toxin (Stx)-producing (STEC) O157:H7 phage type (PT) 24 were identified by the national gastrointestinal disease surveillance system at Public Health England (PHE). Frozen grated coconut imported from India was implicated as the vehicle of infection. Short and long read sequencing data were interrogated for genomic markers to provide evidence that the outbreak strain was from an imported source. The outbreak strain belonged to a sub-lineage (IIa) rare in domestically acquired infection in the United Kingdom, and indicative of an imported strain. Phylogenetic analysis identified the most closely related isolates to the outbreak strain were from cases reporting recent travel not to India, but to Uganda. Phylo-geographical signals based on travel data may be confounded by the failure of local and/or global monitoring systems to capture the full diversity of strains in a given country. This may be due to low prevalence strains circulating in-country under the surveillance radar, or a recent importation event involving the migration of animals and/or people. Comparison of -encoding prophage harbored by the outbreak strain with publicly available -encoding prophage sequences revealed that it was most closely related to -encoding prophage acquired by STEC O157:H7 that caused the first outbreak of STEC-hemolytic uremic syndrome (HUS) in England in 1982-83. Animal and people migration events may facilitate the transfer of -encoding prophage from indigenous STEC O157:H7 to recently imported strains, or vice versa. Monitoring the global transmission of STEC O157:H7 and tracking the exchange of -encoding phage between imported and indigenous strains may provide an early warning of emerging threats to public health.
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http://dx.doi.org/10.3389/fmicb.2020.577658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609406PMC
October 2020

Association between Shiga Toxin-Producing Escherichia coli O157:H7 stx Gene Subtype and Disease Severity, England, 2009-2019.

Emerg Infect Dis 2020 10;26(10):2394-2400

Signs and symptoms of Shiga toxin-producing Escherichia coli (STEC) serogroup O157:H7 infection range from mild gastrointestinal to bloody diarrhea and hemolytic uremic syndrome (HUS). We assessed the association between Shiga toxin gene (stx) subtype and disease severity for »3,000 patients with STEC O157:H7 in England during 2009-2019. Odds of bloody diarrhea, HUS, or both, were significantly higher for patients infected with STEC O157:H7 possessing stx2a only or stx2a combined with other stx subtypes. Odds of severe signs/symptoms were significantly higher for isolates encoding stx2a only and belonging to sublineage Ic and lineage I/II than for those encoding stx2a only and belonging to sublineage IIb, indicating that stx2a is not the only driver causing HUS. Strains of STEC O157:H7 that had stx1a were also significantly more associated with severe disease than strains with stx2c only. This finding confounds public health risk assessment algorithms based on detection of stx2 as a predictor of severe disease.
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http://dx.doi.org/10.3201/eid2610.200319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510717PMC
October 2020

Isolation and characterisation of from fish examined postmortem at ZSL London Zoo between 2014 and 2018.

Vet Rec 2020 Nov 21;187(10):e86. Epub 2020 Aug 21.

Gastrointestinal Bacteria Referral Unit, Public Health England Colindale, London, UK.

Background: When suspect were cultured from fish at ZSL London Zoo, investigations were carried out to determine whether they were possible causes of cholera.

Methods: Bacterial culture was carried out on fish examined postmortem and colonies were identified using standard techniques including the API 20NE biochemical test kits. Suspect isolates were submitted to the Public Health England laboratory for additional testing. Separately, a number of fish were submitted for routine histopathology.

Results: On 13 occasions between 2014 and 2018, suspected were cultured from individuals of eight different freshwater fish species. Archived cultures for eight of these (from six different fish species) were investigated and seven isolates (from five fish species) were confirmed as , but all were non-O1, non-O139 strains. Whole-genome sequencing showed that the five fish species had unique multilocus sequence types (three isolates from were identical), all of which were genetically distant from human isolates.

Conclusions: There was no evidence that these isolates could cause cholera. Histopathological changes consistent with vibriosis were seen in several fish, suggesting that were causing the disease, but there were also concurrent infections or predisposing stress factors.
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http://dx.doi.org/10.1136/vr.105682DOI Listing
November 2020

Investigation into a national outbreak of STEC O157:H7 associated with frozen beef burgers, UK, 2017.

Epidemiol Infect 2020 07 16;148:e215. Epub 2020 Jul 16.

Field Service, National Infections Service, Public Health England, 2 Rivergate, Bristol, UK.

In November 2017, Public Health England identified an outbreak of Shiga toxin-producing Escherichia coli O157:H7 in England where whole genome sequencing results indicated cases were likely to be linked to a common source, and began investigations. Hypothesis generation included a review of enhanced surveillance data, a case-case study and trawling interviews. The hypothesis of interest was tested through the administration of focussed questionnaires and review of shopping history using loyalty card data. Twelve outbreak cases were detected, eight were hospitalised and four developed haemolytic uraemic syndrome. Frozen beef burgers supplied by a national retailer were identified as the vehicle of the outbreak. Testing of two left-over burger samples obtained from the freezers of two separate (unlinked) cases and a retained sample from the production premises were tested and found to be positive for the outbreak strain. A voluntary recall of the burgers was implemented by the retailer. Investigations at the production premises identified no contraventions of food safety legislation. Cooking guidance on the product packaging was deemed to be adequate and interviews with the cases/carers who prepared the burgers revealed no deficiencies in cooking practices at home. Given the long-shelf life of frozen burgers, the product recall likely prevented more cases.
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http://dx.doi.org/10.1017/S0950268820001582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522850PMC
July 2020

Whole genome sequencing and metagenomics for outbreak investigation, source attribution and risk assessment of food-borne microorganisms.

EFSA J 2019 Dec 3;17(12):e05898. Epub 2019 Dec 3.

This Opinion considers the application of whole genome sequencing (WGS) and metagenomics for outbreak investigation, source attribution and risk assessment of food-borne pathogens. WGS offers the highest level of bacterial strain discrimination for food-borne outbreak investigation and source-attribution as well as potential for more precise hazard identification, thereby facilitating more targeted risk assessment and risk management. WGS improves linking of sporadic cases associated with different food products and geographical regions to a point source outbreak and can facilitate epidemiological investigations, allowing also the use of previously sequenced genomes. Source attribution may be favoured by improved identification of transmission pathways, through the integration of spatial-temporal factors and the detection of multidirectional transmission and pathogen-host interactions. Metagenomics has potential, especially in relation to the detection and characterisation of non-culturable, difficult-to-culture or slow-growing microorganisms, for tracking of hazard-related genetic determinants and the dynamic evaluation of the composition and functionality of complex microbial communities. A SWOT analysis is provided on the use of WGS and metagenomics for and Shigatoxin-producing (STEC) serotyping and the identification of antimicrobial resistance determinants in bacteria. Close agreement between phenotypic and WGS-based genotyping data has been observed. WGS provides additional information on the nature and localisation of antimicrobial resistance determinants and on their dissemination potential by horizontal gene transfer, as well as on genes relating to virulence and biological fitness. Interoperable data will play a major role in the future use of WGS and metagenomic data. Capacity building based on harmonised, quality controlled operational systems within European laboratories and worldwide is essential for the investigation of cross-border outbreaks and for the development of international standardised risk assessments of food-borne microorganisms.
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http://dx.doi.org/10.2903/j.efsa.2019.5898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008917PMC
December 2019

Novel multiplex real-time PCR assays reveal a high prevalence of diarrhoeagenic Escherichia coli pathotypes in healthy and diarrhoeal children in the south of Vietnam.

BMC Microbiol 2020 07 3;20(1):192. Epub 2020 Jul 3.

Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) Department of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AW, UK.

Background: Diarrhoeagenic Escherichia coli (DEC) infections are common in children in low-middle income countries (LMICs). However, detecting the various DEC pathotypes is complex as they cannot be differentiated by classical microbiology. We developed four multiplex real-time PCR assays were to detect virulence markers of six DEC pathotypes; specificity was tested using DEC controls and other enteric pathogens. PCR amplicons from the six E. coli pathotypes were purified and amplified to be used to optimize PCR reactions and to calculate reproducibility. After validation, these assays were applied to clinical samples from healthy and diarrhoeal Vietnamese children and associated with clinical data.

Results: The multiplex real-time PCRs were found to be reproducible, and specific. At least one DEC variant was detected in 34.7% (978/2815) of the faecal samples from diarrhoeal children; EAEC, EIEC and atypical EPEC were most frequent Notably, 41.2% (205/498) of samples from non-diarrhoeal children was positive with a DEC pathotype. In this population, only EIEC, which was detected in 34.3% (99/289) of diarrhoeal samples vs. 0.8% (4/498) non-diarrhoeal samples (p < 0.001), was significantly associated with diarrhoea. Multiplex real-time PCR when applied to clinical samples is an efficient and high-throughput approach to DEC pathotypes.

Conclusions: This approach revealed high carriage rates of DEC pathotypes among Vietnamese children. We describe a novel diagnostic approach for DEC, which provides baseline data for future surveillance studies assessing DEC burden in LMICs.
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http://dx.doi.org/10.1186/s12866-020-01878-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333254PMC
July 2020

Tracing Back the Evolutionary Route of Enteroinvasive (EIEC) and Through the Example of the Highly Pathogenic O96:H19 EIEC Clone.

Front Cell Infect Microbiol 2020 3;10:260. Epub 2020 Jun 3.

Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy.

Enteroinvasive (EIEC) cause intestinal illness through the same pathogenic mechanism used by spp. The latter species can be typed through genomic and phenotypic methods used for and have been proposed for reclassification within species. Recently the first appearance of a highly pathogenic EIEC O96:H19 was described in Europe as the causative agent of two large outbreaks that occurred in Italy and in the United Kingdom. In contrast to spp and to the majority of EIEC strains, EIEC O96:H19 fermented lactose, lacked pathoadaptive mutations, and showed good fitness in extracellular environment, similarly to non-pathogenic , suggesting they have emerged following acquisition of the invasion plasmid by a non-pathogenic . Here we describe the whole genome comparison of two EIEC O96:H19 strains isolated from severe cases of diarrhea in Uruguay in 2014 with the sequences of EIEC O96:H19 available in the public domain. The phylogenetic comparison grouped all the O96:H19 strains in a single cluster, while reference EIEC strains branched into different clades with strains occupying apical positions. The comparison of the virulence plasmids showed the presence of a complete conjugation region in at least one O96:H19 EIEC. Reverse Transcriptase Real Time PCR experiments confirmed in this strain the expression of the pilin-encoding gene and conjugation experiments suggested its ability to mobilize an accessory plasmid in a recipient strain. Noteworthy, the region was comprised between two reversely oriented IS elements, which were also found as remnants in another EIEC O96:H19 plasmid lacking the . We hypothesize that an IS-mediated recombination mechanism may have caused the loss of the conjugation region commonly observed in EIEC and virulence plasmids. The results of this study support the hypothesis of EIEC originating from non-pathogenic through the acquisition of the virulence plasmid via conjugation. Remarkably, this study showed the ability of a circulating EIEC strain to mobilize plasmids through conjugation, suggesting a mechanism for the emergence of novel EIEC clones.
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http://dx.doi.org/10.3389/fcimb.2020.00260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283534PMC
June 2021

Microevolution of Campylobacter jejuni during long-term infection in an immunocompromised host.

Sci Rep 2020 06 22;10(1):10109. Epub 2020 Jun 22.

Gastrointestinal Bacteria Reference Unit, Public Health England, Colindale, London, UK.

Campylobacteriosis typically manifests as a short-lived, self-limiting gastrointestinal infection in humans, however prolonged infection can be seen in cases with underlying immunodeficiency. Public Health England received 25 isolates of Campylobacter jejuni from an individual with combined variable immunodeficiency over a period of 15 years. All isolates were typed and archived at the time of receipt. Whole genome sequencing (WGS) and antimicrobial susceptibility testing were performed to examine the relatedness of the isolates and to investigate the changes in the genome that had taken place over the course of the infection. Genomic typing methods were compared to conventional phenotypic methods, and revealed that the infection was caused by a single, persistent strain of C. jejuni belonging to clonal complex ST-45, with evidence of adaptation and selection in the genome over the course of the infection. Genomic analysis of sequence variants associated with antimicrobial resistance identified the genetic background behind rRNA gene mutations causing variable levels of resistance to erythromycin. This application of WGS to examine a persistent case of campylobacteriosis provides insight into the mutations and selective pressures occurring over the course of an infection, some of which have important clinical relevance.
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http://dx.doi.org/10.1038/s41598-020-66771-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308304PMC
June 2020

An outbreak of Shiga toxin-producing Escherichia coli O157:H7 linked to a mud-based obstacle course, England, August 2018.

Zoonoses Public Health 2020 08 21;67(5):467-473. Epub 2020 Jun 21.

Yorkshire and the Humber Health Protection Team, Public Health England, Leeds, UK.

In August 2018, Public Health England (PHE) was made aware of five probable cases of Shiga toxin-producing Escherichia coli (STEC) O157:H7 among individuals reporting participation in a mud-based obstacle race. An additional four cases, identified via routine whole-genome sequencing, were subsequently linked to the same event. Two of the nine cases were due to secondary household transmission. Despite an agreement between the event organizers and the local authority, to ensure that all livestock were removed from the site 28 days before the event, sheep were observed grazing on some of the routes taken by the runners 2 days prior to the race taking place. A retrospective review of incidents reported to PHE between 2015 and 2018 identified 41 cases of gastroenteritis associated with muddy assault course events. Of these, 25 cases were due to infection with STEC O157:H7, of which all but one were associated with outbreaks. Due to the environment in which such events take place, it is impossible to entirely remove the risk of exposure to potentially pathogenic zoonoses. However, race organizers should ensure that livestock are removed from the course 28 days before the event. They should also ensure that participants are made aware of the risk of contracting gastrointestinal disease from the environment, and to stress the importance of hand hygiene post-event and the risk of secondary transmission, particularly to children who are at risk of developing haemolytic uraemic syndrome.
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http://dx.doi.org/10.1111/zph.12744DOI Listing
August 2020

Antimicrobial resistance profiles of diarrhoeagenic isolated from travellers returning to the UK, 2015-2017.

J Med Microbiol 2020 Jul 12;69(7):932-943. Epub 2020 Jun 12.

Gastrointestinal Bacteria Reference Unit, National Infection Service, PHE, 61 Colindale Avenue, London NW9 5EQ, UK.

Diarrhoeagenic (DEC) are difficult to distinguish from non-pathogenic commensal using traditional culture methods. The implementation of PCR targeting specific virulence genes characteristic of the five DEC pathotypes, has improved the detection of DEC in faecal specimens from patients with symptoms of gastrointestinal disease. Antimicrobial resistance (AMR) profiles of 660 strains of DEC isolated between 2015 and 2017 from UK travellers reporting symptoms of gastrointestinal disease were reviewed to look for evidence of emerging AMR associated with travellers' diarrhoea. All isolates of DEC were sequenced, and sequence type, serotype, pathotype markers and AMR profiles were derived from the genome data. A travel history was provided for 54.1 % (357/660) of cases, of which 77.0 % (275/357) reported travel outside the UK within 7 days of onset of symptoms, and 23.0 % (82/357) reported no travel in that time frame. Of the 660 strains of DEC in this study, 265 (40.2 %) samples were identified as EAEC, 48 (7.3 %) as EIEC, 61 (9.2 %) were ETEC and 286 (43.3 %) were EPEC. EPEC caused the highest percentage of infections in children (40.6 %) whilst the highest proportion of cases reporting recent travel were infected with ETEC (86.1 %). There were 390/660 (59.0 %) isolates resistant to at least one antimicrobial on the panel tested (EIEC, 81.3 %; ETEC, =65.6 %; EAEC, =73.2 %; EPEC, 40.9 %) and 265/660 (40.2 %) were multidrug-resistant (EIEC, 33.3 %; ETEC, 32.8 %; EAEC, 56.2 %; EPEC, 28.0 %). Genes conferring resistance to the beta-lactams and fluroquinolones were highest in the EAEC pathotype, 56.6 and 60.7%, respectively. Increasing MDR, along with resistance to the fluroquinolones and the third-generation cephalosporins, in DEC causing travellers' diarrhoea provides further evidence for the need to restrict the use of antimicrobial agents and continuous monitoring.
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http://dx.doi.org/10.1099/jmm.0.001214DOI Listing
July 2020
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