ORCID Profile
0000-0003-2541-8545
Current Organisations
University of Sussex
,
Inha University
,
Imperial College London
,
University Hospitals Sussex NHS Foundation Trust
,
Brighton and Sussex Medical School
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Publications
Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing
Publisher: Elsevier BV
Date: 02-2017
Early analysis of a potential link between viral load and the N501Y mutation in the SARS-COV-2 spike protein
Publisher: Cold Spring Harbor Laboratory
Date: 15-01-2021
DOI: 10.1101/2021.01.12.20249080
Abstract: A new variant of SARS-CoV-2 has emerged which is increasing in frequency, primarily in the South East of England (lineage B.1.1.7 ( 1 ) VUI-202012/01). One potential hypothesis is that infection with the new variant results in higher viral loads, which in turn may make the virus more transmissible. We found higher (sequence derived) viral loads in s les from in iduals infected with the new variant with median inferred viral loads were three-fold higher in in iduals with the new variant. Most of the new variants were s led in Kent and Greater London. We observed higher viral loads in Kent compared to Greater London for both the new variant and other circulating lineages. Outside Greater London, the variant has higher viral loads, whereas within Greater London, the new variant does not have significantly higher viral loads compared to other circulating lineages. Higher variant viral loads outside Greater London could be due to demographic effects, such as a faster variant growth rate compared to other lineages or concentration in particular age-groups. However, our analysis does not exclude a causal link between infection with the new variant and higher viral loads. This is a preliminary analysis and further work is needed to investigate any potential causal link between infection with this new variant and higher viral loads, and whether this results in higher transmissibility, severity of infection, or affects relative rates of symptomatic and asymptomatic infection This is an updated report submitted to NERVTAG in December 2020 as part of urgent investigations into the new variant of SARS-COV-2 (VUI-202012/01). It makes full use of (and is restricted to) all sequence data and associated metadata available to us at the time this original report was submitted and remains provisional. Under normal circumstances more genomes and metadata would be obtained and included before making this report public. We will update this preprint when more genomes and metadata are available and before submitting for peer review.
The impact of viral mutations on recognition by SARS-CoV-2 specific T cells
Publisher: Elsevier BV
Date: 11-2021
Genotypic prediction of anti-microbial susceptibilities in Staphylococcus aureus
Publisher: Elsevier BV
Date: 10-2013
Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation
Publisher: American Society for Microbiology
Date: 07-2017
DOI: 10.1128/JCM.00363-17
Abstract: Whole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks. However, for Staphylococcus aureus , the accumulation of within-host ersity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host ersity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks. We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA). The findings were compared with the routine investigation results and epidemiological evidence. Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC ( P = 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1. We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles however, these had only modestly increased pairwise ersity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) ( P 0.0001). Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype. The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted. Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.
Whole-Genome Sequencing Shows That Patient-to-Patient Transmission Rarely Accounts for Acquisition of Staphylococcus aureus in an Intensive Care Unit
Publisher: Oxford University Press (OUP)
Date: 12-12-2013
DOI: 10.1093/CID/CIT807
Clinical and Microbiological Determinants of Outcome inStaphylococcus aureusBacteraemia
Publisher: Hindawi Limited
Date: 2010
DOI: 10.1155/2010/654858
Abstract: Staphylococcus aureus bacteraemia (SAB) is commonly complicated by metastatic infection or relapse after treatment. Objectives . The study aim was to determine the role of bacterial, host, and management factors in development of complicated SAB. Methods . A prospectively-conducted observational study gathered data on predisposition, management and outcome of 100 consecutive SAB cases. Antibiotic susceptibilities and genetic lineage of bacterial isolates were determined. Further clinical and microbiological data were gathered on two retrospective series from 1999–2000 ( n = 57 ) and 2004 ( n = 116 ). Results . In the prospective cases, 27% met our definition of complicated disease. Expressed as RR and 95% CI, complicated disease was associated with diabetes (1.58, 1.00–2.48), injecting-drug use (5.48, 0.88–33.49), community-onset of symptoms (1.4, 1.02–1.92), and symptom duration ≥ 48 hours prior to starting effective antibiotic therapy (2.10, 1.22–3.61). Uncomplicated disease was associated with the presence of a central line (0.69, 0.55–0.88) and prompt removal of a primary focus (0.71, 0.57–0.90). Neither methicillin resistance nor genetic lineage was associated with complicated disease, but methicillin resistance was associated with higher mortality. Conclusions . This study demonstrates that clinical rather than microbial factors are the major determinants of SAB outcome and underscores the importance of early treatment.
Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England
Publisher: Springer Science and Business Media LLC
Date: 25-03-2021
DOI: 10.1038/S41586-021-03470-X
Abstract: The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England
Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies
Publisher: Springer Science and Business Media LLC
Date: 11-03-2021
DOI: 10.1038/S41586-021-03412-7
Abstract: Transmission of SARS-CoV-2 is uncontrolled in many parts of the world control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant
MAJORA: Continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance
Publisher: Cold Spring Harbor Laboratory
Date: 07-10-2020
DOI: 10.1101/2020.10.06.328328
Abstract: Genomic epidemiology has become an increasingly common tool for epidemic response. Recent technological advances have made it possible to sequence genomes rapidly enough to inform outbreak response, and cheaply enough to justify dense s ling of even large epidemics. With increased availability of sequencing it is possible for agile networks of sequencing facilities to collaborate on the sequencing and analysis of epidemic genomic data. In response to the ongoing SARS-CoV-2 pandemic in the United Kingdom, the COVID-19 Genomics UK (COG-UK) consortium was formed with the aim of rapidly sequencing SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of Majora, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and s le-associated metadata produced across the COG-UK network. The system was designed and implemented pragmatically to stand up capacity rapidly in a pandemic caused by a novel virus. This approach has underpinned the success of COG-UK, which has rapidly become the leading contributor of SARS-CoV-2 genomes to international databases and has generated over 60,000 sequences to date.
Severe infections emerge from commensal bacteria by adaptive evolution
Publisher: eLife Sciences Publications, Ltd
Date: 19-12-2017
DOI: 10.7554/ELIFE.30637
Abstract: Bacteria responsible for the greatest global mortality colonize the human microbiota far more frequently than they cause severe infections. Whether mutation and selection among commensal bacteria are associated with infection is unknown. We investigated de novo mutation in 1163 Staphylococcus aureus genomes from 105 infected patients with nose colonization. We report that 72% of infections emerged from the nose, with infecting and nose-colonizing bacteria showing parallel adaptive differences. We found 2.8-to-3.6-fold adaptive enrichments of protein-altering variants in genes responding to rsp, which regulates surface antigens and toxin production agr, which regulates quorum-sensing, toxin production and abscess formation and host-derived antimicrobial peptides. Adaptive mutations in pathogenesis-associated genes were 3.1-fold enriched in infecting but not nose-colonizing bacteria. None of these signatures were observed in healthy carriers nor at the species-level, suggesting infection-associated, short-term, within-host selection pressures. Our results show that signatures of spontaneous adaptive evolution are specifically associated with infection, raising new possibilities for diagnosis and treatment.
Prediction of Staphylococcus aureus Antimicrobial Resistance by Whole-Genome Sequencing
Publisher: American Society for Microbiology
Date: 04-2014
DOI: 10.1128/JCM.03117-13
Abstract: Whole-genome sequencing (WGS) could potentially provide a single platform for extracting all the information required to predict an organism's phenotype. However, its ability to provide accurate predictions has not yet been demonstrated in large independent studies of specific organisms. In this study, we aimed to develop a genotypic prediction method for antimicrobial susceptibilities. The whole genomes of 501 unrelated Staphylococcus aureus isolates were sequenced, and the assembled genomes were interrogated using BLASTn for a panel of known resistance determinants (chromosomal mutations and genes carried on plasmids). Results were compared with phenotypic susceptibility testing for 12 commonly used antimicrobial agents (penicillin, methicillin, erythromycin, clindamycin, tetracycline, ciprofloxacin, vancomycin, trimethoprim, gentamicin, fusidic acid, rif in, and mupirocin) performed by the routine clinical laboratory. We investigated discrepancies by repeat susceptibility testing and manual inspection of the sequences and used this information to optimize the resistance determinant panel and BLASTn algorithm. We then tested performance of the optimized tool in an independent validation set of 491 unrelated isolates, with phenotypic results obtained in duplicate by automated broth dilution (BD Phoenix) and disc diffusion. In the validation set, the overall sensitivity and specificity of the genomic prediction method were 0.97 (95% confidence interval [95% CI], 0.95 to 0.98) and 0.99 (95% CI, 0.99 to 1), respectively, compared to standard susceptibility testing methods. The very major error rate was 0.5%, and the major error rate was 0.7%. WGS was as sensitive and specific as routine antimicrobial susceptibility testing methods. WGS is a promising alternative to culture methods for resistance prediction in S. aureus and ultimately other major bacterial pathogens.
Severe infections emerge from the microbiome by adaptive evolution
Publisher: Cold Spring Harbor Laboratory
Date: 14-03-2017
DOI: 10.1101/116681
Abstract: Bacteria responsible for the greatest global mortality colonize the human microbiome far more frequently than they cause severe infections. Whether mutation and selection within the microbiome accompany infection is unknown. We investigated de novo mutation in 1163 Staphylococcus aureus genomes from 105 infected patients with nose-colonization. We report that 72% of infections emerged from the microbiome, with infecting and nose-colonizing bacteria showing parallel adaptive differences. We found 2.8-to-3.6-fold enrichments of protein-altering variants in genes responding to rsp , which regulates surface antigens and toxicity agr , which regulates quorum-sensing, toxicity and abscess formation and host-derived antimicrobial peptides. Adaptive mutations in pathogenesis-associated genes were 3.1-fold enriched in infecting but not nose-colonizing bacteria. None of these signatures were observed in healthy carriers nor at the species-level, suggesting disease-associated, short-term, within-host selection pressures. Our results show that infection, like a cancer of the microbiome, emerges through spontaneous adaptive evolution, raising new possibilities for diagnosis and treatment. Life-threatening S. aureus infections emerge from nose microbiome bacteria in association with repeatable adaptive evolution.
Improved contact tracing using network analysis and spatial-temporal proximity
Publisher: Elsevier BV
Date: 03-2022
Lineage replacement and evolution captured by three years of the United Kingdom Covid Infection Survey
Publisher: Cold Spring Harbor Laboratory
Date: 06-01-2022
DOI: 10.1101/2022.01.05.21268323
Abstract: The Office for National Statistics COVID-19 Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced s les collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors. The sweeps also generated an alternating pattern in which most s les had either S-gene target failure (SGTF) or non- SGTF over time. Evolution was characterised by steadily increasing ergence and ersity within lineages, but with step increases in ergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of ersity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens, particularly in the current phase of the pandemic with routine RT-PCR testing now ended in the community.
Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission
Publisher: Springer Science and Business Media LLC
Date: 08-02-2022
DOI: 10.1038/S41467-021-27942-W
Abstract: Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.
SARS-CoV-2 evolution during treatment of chronic infection
Publisher: Springer Science and Business Media LLC
Date: 05-02-2021
RECONSTRUCTING AND PREDICTING THE SPATIAL EVOLUTION OF CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE OUTBREAKS
Publisher: Elsevier BV
Date: 05-2023
Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data
Publisher: Cold Spring Harbor Laboratory
Date: 04-01-2021
DOI: 10.1101/2020.12.30.20249034
Abstract: The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic ersity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England extrapolation to other transmission contexts therefore requires caution.
Characterising contact in disease outbreaks via a network model of spatial-temporal proximity
Publisher: Cold Spring Harbor Laboratory
Date: 09-04-2021
DOI: 10.1101/2021.04.07.21254497
Abstract: Contact tracing is a key tool in epidemiology to identify and control outbreaks of infectious diseases. Existing contact tracing methodologies produce contact maps of in iduals based on a binary definition of contact which can be h ered by missing data and indirect contacts. Here, we present a Spatial-temporal Epidemiological Proximity (StEP) model to recover contact maps in disease outbreaks based on movement data. The StEP model accounts for imperfect data by considering probabilistic contacts between in iduals based on spatial-temporal proximity of their movement trajectories, creating a robust movement network despite possible missing data and unseen transmission routes. Using real-world data we showcase the potential of StEP for contact tracing with outbreaks of multidrug-resistant bacteria and COVID-19 in a large hospital group in London, UK. In addition to the core structure of contacts that can be recovered using traditional methods of contact tracing, the StEP model reveals missing contacts that connect seemingly separate outbreaks. Comparison with genomic data further confirmed that these recovered contacts indeed improve characterisation of disease transmission and so highlights how the StEP framework can inform effective strategies of infection control and prevention.
Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 13-08-2020
DOI: 10.2807/1560-7917.ES.2020.25.32.2001410
Abstract: We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.
Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
Publisher: Elsevier BV
Date: 2021
Do Labor Unions Always Lead to Underinvestment?
Publisher: American Accounting Association
Date: 07-2016
DOI: 10.2308/JMAR-51534
Abstract: We examine the relation between labor union strength and investment efficiency using the comprehensive firm-level data of Korean-listed companies. We find that the perceived underinvestment related to unionization documented in previous studies is attributable to a negative relation between union strength and investment in overinvesting firms. In fact, union strength is positively related to the level of investment in underinvesting firms. We further find that the relation between union strength and investment efficiency is more pronounced for chaebol firms where inefficient investments are more likely due to greater agency problems between the controlling and minority shareholders. Finally, we document that the investment has more positive value implications in firms with a stronger union. Our results suggest that unions play an important role as a nonfinancial stakeholder in curbing inefficient investments. JEL Classifications: G30 G31 J53 J54 M41 M54.
Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus bacteraemia: role of a cryptic variant of an epidemic clone
Publisher: Elsevier BV
Date: 02-2014
Viral burdens are associated with age and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection related sampling bias
Publisher: Cold Spring Harbor Laboratory
Date: 02-12-2022
DOI: 10.1101/2022.12.02.518847
Abstract: In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burdens, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of s les, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. Analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated in iduals with no known prior infection, the average Ct value was 0.94 lower among Alpha variant infections, compared those with the predecessor strain, B.1.177. However, among vaccinated in iduals, it was 0.34 lower among Delta variant infections, compared to those with the Alpha variant. In addition, the average Ct value decreased by 0.20 for every 10 year age increment of the infected in idual. In summary, within-host viral burdens are associated with age, in addition to the interplay of vaccination status and viral variant.
SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2
Publisher: Springer Science and Business Media LLC
Date: 27-07-2022
DOI: 10.1186/S12879-022-07628-4
Abstract: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community s le of in iduals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive in iduals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community s les can augment routine surveillance data without the potential biases introduced due to higher s ling rates of symptomatic in iduals.
Reply to Mills and Linkin
Publisher: Oxford University Press (OUP)
Date: 20-05-2014
DOI: 10.1093/CID/CIU370
Flexible CPA staffing in non‐Big 4 audit firms: Its determinants and implications for audit fees and audit quality
Publisher: Wiley
Date: 06-10-2023
DOI: 10.1111/IJAU.12335
Genomics-informed outbreak investigations of SARS-CoV-2 using civet
Publisher: Cold Spring Harbor Laboratory
Date: 14-12-2021
DOI: 10.1101/2021.12.13.21267267
Abstract: The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 5 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background ersity, resolving the query into different ’catchments’ and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus ersity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health.
Related Organisations
University Of Sussex
Location: United Kingdom of Great Britain and Northern Ireland
Imperial College London
Location: United Kingdom of Great Britain and Northern Ireland
University Hospitals Sussex NHS Foundation Trust
Location: United Kingdom of Great Britain and Northern Ireland
Brighton And Sussex Medical School
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for James Price.