A coliform-targeted metagenomic method facilitating human exposure estimates to Escherichia coli-borne antibiotic resistance genes.

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record.Background: Antimicrobial resistance and the spread of antibiotic resistance genes (ARGs) pose a threat to human health. Community-acquired infections resistant to treatment with first-line antibiotics are increasing, and there are few studies investigating environmental exposures and transmission. Aim: Our objective is to develop a novel targeted metagenomic method to quantify the abundance and diversity of ARGs in a faecal indicator bacterium, and to estimate human exposure to resistant bacteria in a natural environment. Approach: Sequence data from Escherichia coli metagenomes from 13 bathing waters in England were analysed using the ARGs Online Analysis Pipeline to estimate the abundance and diversity of resistance determinants borne by this indicator bacterium. These data were averaged over the 13 sites and used along with data on the levels of E. coli in English bathing waters in 2016 and estimates of the volume of water that water users typically ingest in an average session of their chosen activityto quantify the numbers of ARGs that water users ingest. Findings: Escherichia coli in coastal bathing waters were found to harbour on average 1.24 ARGs per cell. Approximately 2.5 million water sports sessions occurred in England in 2016 that resulted in water users ingesting at least 100 E. coli-borne ARGs.This work was supported by the University of Exeter and the Chinese University of Hong Kong

What is the research evidence for antibiotic resistance exposure and transmission to humans from the environment? A systematic map protocol

This is the final version. Available from the publisher via the DOI in this record.Background: Antimicrobial resistance (AMR) is a public health crisis that is predicted to cause 10 million deaths per year by 2050. The environment has been implicated as a reservoir of AMR and is suggested to play a role in the dissemination of antibiotic resistance genes (ARGs). Currently, most research has focused on measuring concentrations of antibiotics and characterising the abundance and diversity of ARGs and antibiotic resistant bacteria (ARB) in the environment. To date, there has been limited empirical research on whether humans are exposed to this, and whether exposure can lead to measureable impacts on human health. Therefore, the objective of this work is to produce two linked systematic maps to investigate previous research on exposure and transmission of AMR to humans from the environment. The frst map will investigate the available research relating to exposure and transmission of ARB/ARGs from the environment to humans on a global scale and the second will investigate the prevalence of ARB/ARGs in various environments in the UK. These two maps will be useful for policy makers and research funders to identify where there are signifcant gluts and gaps in the current research, and where more primary and synthesis research needs to be undertaken. Methods: Separate search strategies will be developed for the two maps. Searches will be run in 13 databases, and grey literature will be sought from key websites and engagement with experts. Hits will be managed in EndNote and screened in two stages (title/abstract then full text) against predefned inclusion criteria. A minimum of 10% will be double screened with ongoing consistency checking. All included studies will have data extracted into a bespoke form designed and piloted for each map. Data to be extracted will include bibliographic details, study design, location, exposure source, exposure route, health outcome (Map 1); and prevalence/percentage of ARB/ARG (Map 2). No validity appraisal will be undertaken. Results will be tabulated and presented narratively, together with graphics showing the types and areas of research that has been undertaken and heatmaps for key exposure-health outcomes (Map 1) and exposure-prevalence (Map 2).Natural Environment Research Council (NERC

A cross-sectional study on the prevalence of illness in coastal bathers compared to non-bathers in England and Wales: Findings from the Beach User Health Survey

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The risks of illness associated with bathing in UK coastal waters have not been quantified since the early 1990s. Efforts have been made since then to improve the quality of bathing waters. The aim of this study was to quantify the prevalence of symptoms of illness associated with sea bathing in bathers in England and Wales. A cross-sectional study was conducted between June 2014 and April 2015. An online survey collected information from sea bathers and non-bathers on their visits to beaches in England and Wales along with the occurrence of symptoms of illness. 2631 people (1693 bathers, 938 non-bathers) responded to the survey. Compared to non-bathers, bathers were more likely to report skin ailments (adjusted prevalence odds ratio (AOR) = 2.64, 95% confidence interval (CI) 1.23 to 5.65, p = 0.01), ear ailments (AOR = 3.77, 95% CI 1.84 to 7.73, p < 0.001), and any symptoms of illness (AOR = 3.73, 95% CI 2.63 to 5.29, p < 0.001). There was weak evidence of an increase in the odds of gastrointestinal illness (AOR = 1.59, 95% CI 0.96 to 2.65, p = 0.07), respiratory ailments (AOR = 2.44, 95% CI 0.92 to 6.48, p = 0.07) and eye ailments (AOR = 2.12, 95% CI 0.83 to 5.39, p = 0.11). While the study design does not allow inference of causality, we do observe an association between sea bathing in England and Wales and reported symptoms of ill health. This suggests that despite higher rates of compliance with water quality criteria among bathing waters nowadays, the odds of illness for bathers relative to non-bathers is similar in magnitude to estimates made in the 1990s.Natural Environment Research Council (NERC)European Regional Development FundNational Institute for Health Researc

Existing evidence on antibiotic resistance exposure and transmission to humans from the environment: a systematic map

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials; All data is provided as additional files.Background Antimicrobial resistance (AMR) is predicted to become the leading cause of death by 2050 with antibiotic resistance being an important component. Anthropogenic pollution introduces antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) to the natural environment. Currently, there is limited empirical evidence demonstrating whether humans are exposed to environmental AMR and whether this exposure can result in measurable human health outcomes. In recent years there has been increasing interest in the role of the environment and disparate evidence on transmission of AMR to humans has been generated but there has been no systematic attempt to summarise this. We aim to create two systematic maps that will collate the evidence for (1) the transmission of antibiotic resistance from the natural environment to humans on a global scale and (2) the state of antibiotic resistance in the environment in the United Kingdom. Methods Search strategies were developed for each map. Searches were undertaken in 13 bibliographic databases. Key websites were searched and experts consulted for grey literature. Search results were managed using EndNote X8. Titles and abstracts were screened, followed by the full texts. Articles were double screened at a minimum of 10% at both stages with consistency checking and discussion when disagreements arose. Data extraction occurred in Excel with bespoke forms designed. Data extracted from each selected study included: bibliographic information; study site location; exposure source; exposure route; human health outcome (Map 1); prevalence/percentage/abundance of ARB/antibiotic resistance elements (Map 2) and study design. EviAtlas was used to visualise outputs. Results For Map 1, 40 articles were included, from 11,016 unique articles identified in searches, which investigated transmission of AMR from the environment to humans. Results from Map 1 showed that consumption/ingestion was the most studied transmission route. Exposure (n = 17), infection (n = 16) and colonisation (n = 11) being studied as an outcome a similar number of times, with mortality studied infrequently (n = 2). In addition, E. coli was the most highly studied bacterium (n = 16). For Map 2, we included 62 studies quantifying ARB or resistance elements in the environment in the UK, from 6874 unique articles were identified in the searches. The most highly researched species was mixed communities (n = 32). The most common methodology employed in this research question was phenotypic testing (n = 37). The most commonly reported outcome was the characterisation of ARBs (n = 40), followed by characterisation of ARGs (n = 35). Other genetic elements, such as screening for intI1 (n = 15) (which encodes a Class 1 integron which is used as a proxy for environmental ARGs) and point mutations (n = 1) were less frequently reported. Both maps showed that research was focused towards aquatic environments. Conclusions Both maps can be used by policy makers to show the global (Map 1) and UK (Map 2) research landscapes and provide an overview of the state of AMR in the environment and human health impacts of interacting with the environment. We have also identified (1) clusters of research which may be used to perform meta-analyses and (2) gaps in the evidence base where future primary research should focus.Natural Environment Research Council (NERC

The complex interplay between antibiotic resistance and pharmaceutical and personal care products in the environment.

This is the final version. Available from Wiley via the DOI in this record. Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are important environmental contaminants. Nonetheless, what drives the evolution, spread, and transmission of antibiotic resistance dissemination is still poorly understood. The abundance of ARB and ARGs is often elevated in human-impacted areas, especially in environments receiving fecal wastes, or in the presence of complex mixtures of chemical contaminants, such as pharmaceuticals and personal care products. Self-replication, mutation, horizontal gene transfer, and adaptation to different environmental conditions contribute to the persistence and proliferation of ARB in habitats under strong anthropogenic influence. Our review discusses the interplay between chemical contaminants and ARB and their respective genes, specifically in reference to co-occurrence, potential biostimulation, and selective pressure effects, and gives an overview of mitigation by existing man-made and natural barriers. Evidence and strategies to improve the assessment of human health risks due to environmental antibiotic resistance are also discussed.Portuguese Foundation for Science and Technology (FCT)European Union's Horizon 202Australian Research CouncilAustralian Research CouncilNatural Environment Research CouncilFCT/Ministry of Science, Technology, and Higher EducationFCT/Ministry of Science, Technology, and Higher EducationFCT/Ministry of Science, Technology, and Higher Educatio

Exposure to and colonisation by antibiotic-resistant E. coli in UK coastal water users: environmental surveillance, exposure assessment, and epidemiological study (Beach Bum Survey) (article)

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record. The dataset associated with this article is located in ORE at: http://hdl.handle.net/10871/30448BACKGROUND: Antibiotic-resistant bacteria (ARB) present a global public health problem. With numbers of community-acquired resistant infections increasing, understanding the mechanisms by which people are exposed to and colonised by ARB can help inform effective strategies to prevent their spread. The role natural environments play in this is poorly understood. This is the first study to combine surveillance of ARB in bathing waters, human exposure estimates and association between exposure and colonisation by ARB in water users. METHODS: 97 bathing water samples from England and Wales were analysed for the proportion of E. coli harbouring blaCTX-M. These data were used to estimate the likelihood of water users ingesting blaCTX-M-bearing E. coli. Having identified surfers as being at risk of exposure to ARB, a cross-sectional study was conducted. Regular surfers and non-surfers were recruited to assess whether there is an association between surfing and gut colonisation by blaCTX-M-bearing E. coli. RESULTS: 11 of 97 bathing waters sampled were found to contain blaCTX-M-bearing E. coli. While the percentage of blaCTX-M-bearing E. coli in bathing waters was low (0.07%), water users are at risk of ingesting these ARB. It is estimated that over 25 million water sports sessions occurred in 2015 resulting in the ingestion of at least one blaCTX-M-bearing E. coli. In the epidemiological survey, 9/143 (6.3%) surfers were colonised by blaCTX-M-bearing E. coli, as compared to 2/130 (1.5%) of non-surfers (risk ratio=4.09, 95% CI 1.02 to 16.4, p=0.046). CONCLUSIONS: Surfers are at risk of exposure to and colonisation by clinically important antibiotic-resistant E. coli in coastal waters. Further research must be done on the role natural environments play in the transmission of ARB.This work was supported by the European Regional Development Fund [grant number 500020], and Lihong Zhang was supported by the Natural Environment Research Council [grant number NE/M011259/ 1

Grasping motor impairments in autism: Not action planning but movement execution is deficient

Contains fulltext : 125501.pdf (publisher's version ) (Closed access)Different views on the origin of deficits in action chaining in autism spectrum disorders (ASD) have been posited, ranging from functional impairments in action planning to internal models supporting motor control. Thirty-one children and adolescents with ASD and twenty-nine matched controls participated in a two-choice reach-to-grasp paradigm wherein participants received cueing information indicating either the object location or the required manner of grasping. A similar advantage for location cueing over grip cueing was found in both groups. Both accuracy and reaction times of the ASD group were indistinguishable from the control group. In contrast, movement times of the ASD group were significantly delayed in comparison with controls. These findings suggest that movement execution rather than action planning is deficient in ASD, and that deficits in action chaining derive from impairments in internal action models supporting action execution