Biography
Career
- 2020–present NIHR Clinical Lecturer in Virology, Department of Pathology, University of Cambridge
- 2020–present Honorary Specialty Registrar in Infectious Diseases and Medical Virology, Cambridge University Hospitals
- 2021–present Senior Postdoctoral Researcher, Trinity College, Cambridge
- 2019–2020 Mason Medical Research Fellow, Department of Applied Mathematics and Theoretical Physics, University of Cambridge
- 2019–2020 Honorary Specialty Registrar in Infectious Diseases and Medical Microbiology, Cambridge University Hospitals
- 2018–2019 Specialty Registrar in Infectious Diseases and Medical Microbiology, Cambridge University Hospitals
- 2015–2018 Academic Clinical Fellow in Infectious Diseases, East of England Deanery
- 2013–2015 Academic Foundation Programme doctor, Brighton and Sussex University Hospitals
- 2009–2013 Student, Cambridge Graduate Course in Medicine
- 2006–2009 Ph.D. in theoretical physics, Department of Applied Mathematics and Theoretical Physics, University of Cambridge
Research
Here following media coverage on pandemic preparedness?
There will be more pandemics - the only question is when. We need to make sure the systems we build in preparation for the next pandemic are still working when it comes, whether that is in a year, five years, ten years, or a hundred years. If you want to read more, look at this article for further detail on building surge capacity in diagnostic services. I am happy to be contacted by people in the media or working in policy to discuss these broader issues, or additional detail of diagnostic plans. Please understand that I receive a lot of mail and sadly cannot always reply to everything I receive from members of the public.
Research Interests (what I normally do!)
I am a clinical academic. My research interests lie at the interface between mathematics and molecular virology. I work to develop and apply novel signal processing algorithms to viral genetic data, aiming to discover previously unrecognised regions of structural and/or functional importance in viruses. This allows us to understand better the life cycle of these viruses and so focus on how we can disrupt the life cycle and avoid, attenuate or cure disease. As with many virologists I have spent some time working on SARS-CoV-2 (the virus that causes COVID-19) recently, but I also have interests in flaviviruses (a group of viruses including, amongst others, dengue, Zika, yellow fever and tick-borne encephalitis viruses) and HIV.
I have additional interests in ensuring clinical diagnostic services can cope with additional demand during emergencies, such as pandemics, and in optimising use of clinical diagnostics for patient care.
Publications
Virus genetics
- Locations and structures of influenza A virus packaging-associated signals and other functional elements via an in silico pipeline for predicting constrained features in RNA viruses
Emma Beniston, Jordan P. SkittrallAbstract
Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging-associated regions, and their structures, by applying a recently-improved pipeline for delineating constrained regions in RNA viruses and applying structural prediction algorithms. We find and characterise other known constrained regions within influenza A genomes, including the region associated with the PA-X frameshift, regions associated with alternative splicing, and constraint around the initiation motif for a truncated PB1 protein, PB1-N92, associated with avian viruses. We further predict the presence of constrained regions that have not previously been described. The extra characterisation our work provides allows investigation of these key regions for drug target potential, and points towards determinants of packaging compatibility between segments.
PLoS Computational Biology 2024;20(4):e1012009. doi:10.1371/journal.pcbi.1012009 - A novel approach to finding conserved features in low‐variability gene alignments characterises RNA motifs in SARS‐CoV and SARS‐CoV‐2
Jordan P. Skittrall, Nerea Irigoyen, Ian Brierley, Julia R. Gog
Abstract
Collections of genetic sequences belonging to related organisms contain information on the evolutionary constraints to which the organisms have been subjected. Heavily constrained regions can be investigated to understand their roles in an organism’s life cycle, and drugs can be sought to disrupt these roles. In organisms with low genetic diversity, such as newly-emerged pathogens, it is key to obtain this information early to develop new treatments. Here, we present methods that ensure we can leverage all the information available in a low-signal, low-noise set of sequences, to find contiguous regions of relatively conserved nucleic acid. We demonstrate the application of these methods by analysing over 5 million genome sequences of the recently-emerged RNA virus SARS-CoV-2 and correlating these results with an analysis of 119 genome sequences of SARS-CoV. We propose the precise location of a previously described packaging signal, and discuss explanations for other regions of high conservation.
Scientific Reports 2023;13:12079. doi:10.1038/s41598-023-39207-1 PMID: 37495730 - A scale-free analysis of the HIV-1 genome demonstrates multiple conserved regions of structural and functional importance
Jordan P. Skittrall, Carin K. Ingemarsdotter, Julia R. Gog, Andrew M. L. Lever
Abstract
HIV-1 replicates via a low-fidelity polymerase with a high mutation rate; strong conservation of individual nucleotides is highly indicative of the presence of critical structural or functional properties. Identifying such conservation can reveal novel insights into viral behaviour. We analysed 3651 publicly available sequences for the presence of nucleic acid conservation beyond that required by amino acid constraints, using a novel scale-free method that identifies regions of outlying score together with a codon scoring algorithm. Sequences with outlying score were further analysed using an algorithm for producing local RNA folds whilst accounting for alignment properties. 11 different conserved regions were identified, some corresponding to well-known cis-acting functions of the HIV-1 genome but also others whose conservation has not previously been noted. We identify rational causes for many of these, including cis functions, possible additional reading frame usage, a plausible mechanism by which the central polypurine tract primes second-strand DNA synthesis and a conformational stabilising function of a region at the 5′ end of env.
PLoS Computational Biology 2019;15(9):e1007345. doi:10.1371/journal.pcbi.1007345
PMID: 31545786
Pandemic preparedness
- Preparing for the next pandemic: reserve laboratory staff are crucial
Jordan P. Skittrall, Neil Bentley, Tim Wreghitt, Paul Silverston, Huina Yang, Sani H. Aliyu, Anna A. SmielewskaAbstract
Lack of laboratory staff was an important obstacle in scaling up covid-19 testing. Jordan Skittrall and colleagues consider how we can be better prepared in future.
BMJ 2022;378:e072467. doi:10.1136/bmj-2022-072467
PMID: 36167409
Understanding and optimising diagnostics for patient care
- Specificity and positive predictive value of SARS-CoV-2 nucleic acid amplification testing in a low-prevalence setting
Jordan P. Skittrall, Michael Wilson, Anna A. Smielewska, Surendra Parmar, Mary D. Fortune, Dominic Sparkes, Martin D. Curran, Hongyi Zhang, Hamid JalalAbstract
Objectives: When the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is low, many positive test results are false positives. Confirmatory testing reduces overdiagnosis and nosocomial infection and enables real-world estimates of test specificity and positive predictive value. This study estimates these parameters to evaluate the impact of confirmatory testing and to improve clinical diagnosis, epidemiological estimation and interpretation of vaccine trials.
Methods: Over 1 month we took all respiratory samples from our laboratory with a patient's first detection of SARS-CoV-2 RNA (Hologic Aptima SARS-CoV-2 assay or in-house RT-PCR platform), and repeated testing using two platforms. Samples were categorized by source, and by whether clinical details suggested COVID-19 or corroborative testing from another laboratory. We estimated specificity and positive predictive value using approaches based on maximum likelihood.
Results: Of 19 597 samples, SARS-CoV-2 RNA was detected in 107; 52 corresponded to first-time detection (0.27% of tests on samples without previous detection). Further testing detected SARS-CoV-2 RNA once or more (‘confirmed’) in 29 samples (56%), and failed to detect SARS-CoV-2 RNA (‘not confirmed’) in 23 (44%). Depending upon assumed parameters, point estimates for specificity and positive predictive value were 99.91–99.98% and 61.8–89.8% respectively using the Hologic Aptima SARS-CoV-2 assay, and 97.4–99.1% and 20.1–73.8% respectively using an in-house assay.
Conclusions: Nucleic acid amplification testing for SARS-CoV-2 is highly specific. Nevertheless, when prevalence is low a significant proportion of initially positive results fail to confirm, and confirmatory testing substantially reduces the detection of false positives. Omitting additional testing in samples with higher prior detection probabilities focuses testing where it is clinically impactful and minimizes delay.
Clinical Microbiolgy and Infection (2020). doi:10.1016/j.cmi.2020.10.003
PMID: 33068757 - Diagnostic tool or screening programme? Asymptomatic testing for SARS-CoV-2 needs clear goals and protocols
Jordan P. Skittrall, Mary D. Fortune, Hamid Jalal, Hongyi Zhang, David A. Enoch, Nicholas M. Brown, Anne Swift
The Lancet Regional Health – Europe (2021) 1 100002. doi:10.1016/j.lanepe.2020.100002
PMID: 34173617
The following is a complete list of my publications, including those in the “key publications” section above. I aim to keep this list of infection and medical publications up to date, but sometimes fall behind, in which case my ORCID profile or my Google Scholar profile may have more information.
- Locations and structures of influenza A virus packaging-associated signals and other functional elements via an in silico pipeline for predicting constrained features in RNA viruses
Emma Beniston, Jordan P. SkittrallAbstract
Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging-associated regions, and their structures, by applying a recently-improved pipeline for delineating constrained regions in RNA viruses and applying structural prediction algorithms. We find and characterise other known constrained regions within influenza A genomes, including the region associated with the PA-X frameshift, regions associated with alternative splicing, and constraint around the initiation motif for a truncated PB1 protein, PB1-N92, associated with avian viruses. We further predict the presence of constrained regions that have not previously been described. The extra characterisation our work provides allows investigation of these key regions for drug target potential, and points towards determinants of packaging compatibility between segments.
PLoS Computational Biology 2024;20(4):e1012009. doi:10.1371/journal.pcbi.1012009 - A novel approach to finding conserved features in low‐variability gene alignments characterises RNA motifs in SARS‐CoV and SARS‐CoV‐2
Jordan P. Skittrall, Nerea Irigoyen, Ian Brierley, Julia R. Gog
Abstract
Collections of genetic sequences belonging to related organisms contain information on the evolutionary constraints to which the organisms have been subjected. Heavily constrained regions can be investigated to understand their roles in an organism’s life cycle, and drugs can be sought to disrupt these roles. In organisms with low genetic diversity, such as newly-emerged pathogens, it is key to obtain this information early to develop new treatments. Here, we present methods that ensure we can leverage all the information available in a low-signal, low-noise set of sequences, to find contiguous regions of relatively conserved nucleic acid. We demonstrate the application of these methods by analysing over 5 million genome sequences of the recently-emerged RNA virus SARS-CoV-2 and correlating these results with an analysis of 119 genome sequences of SARS-CoV. We propose the precise location of a previously described packaging signal, and discuss explanations for other regions of high conservation.
Scientific Reports 2023;13:12079. doi:10.1038/s41598-023-39207-1 - Multiplex MinION sequencing suggests enteric adenovirus F41 genetic diversity comparable to pre-COVID-19 era
Mailis Maes, Fahad Khokhar, Sam A.J. Wilkinson, Andrew D. Smith, Ganna Kovalenko, Gordon Dougan, Joshua Quick, Nicholas J. Loman, Stephen Baker, Martin D. Curran, Jordan P. Skittrall, Charlotte J. Houldcroft
Abstract
Human adenovirus F41 causes acute gastroenteritis in children, and has recently been associated with an apparent increase in paediatric hepatitis of unknown aetiology in the UK, with further cases reported in multiple countries. Relatively little is known about the genetic diversity of adenovirus F41 in UK children; and it is unclear what, if any, impact the COVID-19 pandemic has had on viral diversity in the UK. Methods that allow F41 to be sequenced from clinical samples without the need for viral culture are required to provide the genomic data to address these questions. Therefore, we evaluated an overlapping-amplicon method of sequencing adenovirus genomes from clinical samples using Oxford Nanopore technology. We applied this method to a small sample of adenovirus-species-F-positive extracts collected as part of standard care in the East of England region in January–May 2022. This method produced genomes with >75% coverage in 13/22 samples and >50% coverage in 19/22 samples. We identified two F41 lineages present in paediatric patients in the East of England in 2022. Where F41 genomes from paediatric hepatitis cases were available (n=2), these genomes fell within the diversity of F41 from the UK and continental Europe sequenced before and after the 2020–2021 phase of the COVID-19 pandemic. Our analyses suggest that overlapping amplicon sequencing is an appropriate method for generating F41 genomic data from high-virus-load clinical samples, and currently circulating F41 viral lineages were present in the UK and Europe before the COVID-19 pandemic.
Microbial Genomics 2023;9:000920. doi:10.1099/mgen.0.000920 - Preparing for the next pandemic: reserve laboratory staff are crucial
Jordan P. Skittrall, Neil Bentley, Tim Wreghitt, Paul Silverston, Huina Yang, Sani H. Aliyu, Anna A. Smielewska
Abstract
Lack of laboratory staff was an important obstacle in scaling up covid-19 testing. Jordan Skittrall and colleagues consider how we can be better prepared in future.
BMJ 2022;378:e072467. doi:10.1136/bmj-2022-072467
PMID: 36167409 - Serology versus nucleic acid amplification to diagnose acute hepatitis E, United Kingdom, 2014–18
Jordan P. Skittrall, Hamid Jalal
Abstract
Objectives: Diagnosing hepatitis E infection usually involves specific IgM testing, but sensitivity/specificity concerns mean many guidelines and practices include confirmatory tests. We studied whether additional information confirmatory tests provide justifies their use.
Methods: We examined 9131 records of anti-hepatitis E IgM assays, 7615 of IgG assays, and 1726 of RT-PCR assays from our regional laboratory, spanning October 2014–October 2018. We paired 495 IgM assay results with a RT-PCR result. We examined whether IgM results predicted PCR results, reviewed discrepant pairs, and investigated the correlation between IgG and PCR results in patients with strongly reactive IgM assays.
Results: Anti-hepatitis E IgM titres are bimodal. A high cut-off value optimises prediction of RNA detectability. 7/404 low-IgM samples had detectable RNA, 6 from immunosuppressed patients. 26/91 high-IgM samples did not have detectable RNA. In high-IgM samples, RNA detectability was not associated with IgG titre (one-tailed Mann-Whitney U test, p = 0.14).
Conclusions: In immunocompetent patients, tests beyond IgM seldom add clinically useful information. In patients with immunocompromise, IgM and RNA could contribute information. Additional tests' extra costs/intervention delays cannot be justified. IgM assay cut-offs should reflect titres' bimodal distribution, with values standardised using international units.
Journal of Infection, 2022 85 327–333. doi:10.1016/j.jinf.2022.06.017
PMID: 35753571 - SARS-CoV-2 screening: effectiveness and risk of increasing transmission
Jordan P. Skittrall
Abstract
Testing asymptomatic people for SARS-CoV-2 aims to reduce COVID-19 transmission. Screening programmes' effectiveness depends upon testing strategy, sample handling logistics, test sensitivity and individual behaviour, in addition to dynamics of viral transmission. The interaction between these factors is not fully characterized. We investigated the interaction between these factors to determine how to optimize reduction of transmission. We estimate that under idealistic assumptions 70% of transmission may be averted, but under realistic assumptions only 7% may be averted. We show that programmes that overwhelm laboratory capacity or reduce isolation of those with minor symptoms have increased transmission compared with those that do not: programmes need to be designed to avoid these issues, or they will be ineffective or even counter-productive. Our model allows optimal selection of whom to test, quantifies the balance between accuracy and timeliness, and quantifies potential impacts of behavioural interventions. We anticipate our model can be used to understand optimal screening strategies for other infectious diseases with substantially different dynamics.
Journal of the Royal Society Interface, 2021 18(180) 20210164. doi:10.1098/rsif.2021.0164
PMID: 34283945 - Azithromycin susceptibility testing of Salmonella enterica serovar Typhi: impact on management of enteric fever
Jordan P. Skittrall, David Levy, Christian Obichukwu, Amy Gentle, Marie A. Chattaway, David Hayns, Clare Etheridge, Christopher M. Parry, Vanessa Wong, James Whitehorn
Abstract
Background: Drug-resistant enteric fever is increasingly common in the Indian subcontinent. Correctly determining azithromycin resistance matters where drug-resistant enteric fever is common and oral therapy necessary.
Case report: In two patients returning from Pakistan to the UK with cephalosporin-resistant Salmonella enterica serovar Typhi, gradient strip testing erroneously indicated azithromycin resistance; the errors were detected by repeat testing and confirmed by whole genome sequencing.
Results: Both patients were treated with meropenem and, when revised susceptibility results were known, with azithromycin, allowing a switch to oral therapy.
Conclusion: As cephalosporin resistance becomes more common, azithromycin will be key for treating enteric fever and optimizing practice in susceptibility testing will be crucial. Practitioners should be aware of key steps to minimize error in azithromycin susceptibility testing, and should be alert for possible errors when reported azithromycin resistance is discordant with known prevalence of resistance.
Clinical Infection in Practice (2021) 10 100069. doi:10.1016/j.clinpr.2021.100069 - SARS-CoV-2 evolution during treatment of chronic infection
Steven A. Kemp, Dami A. Collier, Rawlings P. Datir, Isabella A.T.M. Ferreira, Salma Gayed, Aminu Jahun, Myra Hosmillo, Choe Rees-Spear, Petra Mlocochova, Ines Ushiro Lumb, David J. Roberts, Anita Chandra, Nigel Temperton, The CITIID-NIHR BioResource COVID-19 Collaboration, The COVID-19 Genomics UK (COG-UK) Consortium, Katherine Sharrocks, Elizabeth Blane, Yorgo Modis, Kendra Leigh, John Briggs, Marit van Gils, Kenneth G.C. Smith, John R. Bradley, Chris Smith, Rainer Doffinger, Lourdes Ceron-Gutierrez, Gabriela Barcenas-Morales, David D. Pollock, Richard A. Goldstein, Anna Smielewska, Jordan P. Skittrall, Theodore Goulioris, Ian G. Goodfellow, Effrossyni Gkrania-Klotsas, Christopher J.R. Illingworth, Laura E. McCoy, Ravindra K. Gupta
Abstract
SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.
Nature (2021) 592(7853) 277–282. doi:10.1038/s41586-021-03291-y
PMID: 33545711 - Diagnostic tool or screening programme? Asymptomatic testing for SARS-CoV-2 needs clear goals and protocols
Jordan P. Skittrall, Mary D. Fortune, Hamid Jalal, Hongyi Zhang, David A. Enoch, Nicholas M. Brown, Anne Swift
The Lancet Regional Health – Europe (2021) 1 100002. doi:10.1016/j.lanepe.2020.100002
PMID: 34173617 - Specificity and positive predictive value of SARS-CoV-2 nucleic acid amplification testing in a low-prevalence setting
Jordan P. Skittrall, Michael Wilson, Anna A. Smielewska, Surendra Parmar, Mary D. Fortune, Dominic Sparkes, Martin D. Curran, Hongyi Zhang, Hamid Jalal
Abstract
Objectives: When the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is low, many positive test results are false positives. Confirmatory testing reduces overdiagnosis and nosocomial infection and enables real-world estimates of test specificity and positive predictive value. This study estimates these parameters to evaluate the impact of confirmatory testing and to improve clinical diagnosis, epidemiological estimation and interpretation of vaccine trials.
Methods: Over 1 month we took all respiratory samples from our laboratory with a patient's first detection of SARS-CoV-2 RNA (Hologic Aptima SARS-CoV-2 assay or in-house RT-PCR platform), and repeated testing using two platforms. Samples were categorized by source, and by whether clinical details suggested COVID-19 or corroborative testing from another laboratory. We estimated specificity and positive predictive value using approaches based on maximum likelihood.
Results: Of 19 597 samples, SARS-CoV-2 RNA was detected in 107; 52 corresponded to first-time detection (0.27% of tests on samples without previous detection). Further testing detected SARS-CoV-2 RNA once or more (‘confirmed’) in 29 samples (56%), and failed to detect SARS-CoV-2 RNA (‘not confirmed’) in 23 (44%). Depending upon assumed parameters, point estimates for specificity and positive predictive value were 99.91–99.98% and 61.8–89.8% respectively using the Hologic Aptima SARS-CoV-2 assay, and 97.4–99.1% and 20.1–73.8% respectively using an in-house assay.
Conclusions: Nucleic acid amplification testing for SARS-CoV-2 is highly specific. Nevertheless, when prevalence is low a significant proportion of initially positive results fail to confirm, and confirmatory testing substantially reduces the detection of false positives. Omitting additional testing in samples with higher prior detection probabilities focuses testing where it is clinically impactful and minimizes delay.
Clinical Microbiolgy and Infection (2020). doi:10.1016/j.cmi.2020.10.003
PMID: 33068757 - Point of care nucleic acid testing for SARS-CoV-2 in hospitalised patients: a clinical validation trial and implementation study
Dami A. Collier, Sonny M. Assennato, Ben Warne, Nyarie Sithole, Katherine Sharrocks, Allyson Ritchie, Pooja Ravji, Matthew Routledge, Dominic Sparkes, Jordan Skittrall, Anna Smielewska, Isobel Ramsey, Neha Goel, Martin Curran, David Enoch, Rhys Tassell, Michelle Lineham, Devan Vaghela, Clare Leong, Hoi Ping Mok, John Bradley, Kenneth G.C. Smith, Vivienne Mendoza, Nikos Demiris, Martin Besser, Gordon Dougan, Paul J. Lehner, Mark J. Siedner, Hongyi Zhang, Claire S. Waddington, Helen Lee, Ravindra K. Gupta, CITIID-NIHR COVID BioResource Collaboration
Abstract
There is an urgent need for rapid SARS-CoV-2 testing in hospitals to limit nosocomial spread. We report an evaluation of point of care (POC) nucleic acid amplification testing (NAAT) in 149 participants with parallel combined nasal and throat swabbing for POC versus standard lab RT-PCR testing. Median time to result is 2.6 (IQR 2.3–4.8) versus 26.4 h (IQR 21.4–31.4, p < 0.001), with 32 (21.5%) positive and 117 (78.5%) negative. Cohen’s κ correlation between tests is 0.96 (95% CI 0.91–1.00). When comparing nearly 1,000 tests pre- and post-implementation, the median time to definitive bed placement from admission is 23.4 (8.6–41.9) versus 17.1 h (9.0–28.8), p = 0.02. Mean length of stay on COVID-19 “holding” wards is 58.5 versus 29.9 h (p < 0.001). POC testing increases isolation room availability, avoids bed closures, allows discharge to care homes, and expedites access to hospital procedures. POC testing could mitigate the impact of COVID-19 on hospital systems.
Cell Reports Medicine (2020) 1(5) 100062. doi:10.1016/j.xcrm.2020.100062
PMID: 32838340 - Higher incidence but similar outcomes from bloodstream infections in people with type 2 diabetes mellitus: a retrospective case-controlled analysis
A.N. Bryce, R. Phillips, J.P. Skittrall, A.J. Chakera, J.K. McLoughlin, C.S. Sargent
Abstract
Aims: People with type 2 diabetes mellitus are more susceptible to infections. This study aimed to compare the microbiology, incidence and clinical outcome of bloodstream infections (BSIs) in people with type 2 diabetes and matched controls amongst a cohort of hospital inpatients in the United Kingdom.
Methods: A retrospective analysis was conducted on all positive blood cultures obtained over a one-year period, identifying inpatients with type 2 diabetes and BSIs (n = 151). Matched controls were collated from the same cohort. Admission data were obtained from clinical coding. Patient outcomes were analysed in terms of 90-day mortality, length of stay (LOS) and admission rate to high or intensive dependency units (HDU/ICU). Microbial culture and clinical source of infection were compared between groups.
Results: Patients with type 2 diabetes comprised 10.6% of admissions but 21.1% (n = 151) of analysed BSIs (OR: 2.27, p < .001). Similar 90-day mortality rates were seen between people with type 2 diabetes (D) and controls (C) (D: 23/151, C: 28/151, p = .54). Mean LOS was also similar (D: 19.8 days, C: 21.1 days p = .62). In both groups, Escherichia coli was the most commonly isolated organism (D: 64/173, C: 55/171) and the urinary tract the most common identified primary site of BSI (D: 47/151, C: 45/151).
Conclusions: Whilst inpatients with type 2 diabetes have increased odds of experiencing BSIs, our single-centre study suggests a diagnosis of type 2 diabetes does not necessarily confer a worse outcome.
Clinical Infection in Practice 7–8 100030. doi:10.1016/j.clinpr.2020.100030 - A scale-free analysis of the HIV-1 genome demonstrates multiple conserved regions of structural and functional importance
Jordan P. Skittrall, Carin K. Ingemarsdotter, Julia R. Gog, Andrew M. L. Lever
Abstract
HIV-1 replicates via a low-fidelity polymerase with a high mutation rate; strong conservation of individual nucleotides is highly indicative of the presence of critical structural or functional properties. Identifying such conservation can reveal novel insights into viral behaviour. We analysed 3651 publicly available sequences for the presence of nucleic acid conservation beyond that required by amino acid constraints, using a novel scale-free method that identifies regions of outlying score together with a codon scoring algorithm. Sequences with outlying score were further analysed using an algorithm for producing local RNA folds whilst accounting for alignment properties. 11 different conserved regions were identified, some corresponding to well-known cis-acting functions of the HIV-1 genome but also others whose conservation has not previously been noted. We identify rational causes for many of these, including cis functions, possible additional reading frame usage, a plausible mechanism by which the central polypurine tract primes second-strand DNA synthesis and a conformational stabilising function of a region at the 5′ end of env.
PLoS Computational Biology 15(9):e1007345. doi:10.1371/journal.pcbi.1007345
PMID: 31545786 - Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea
D. Mawer, F. Byrne, S. Drake, C. Brown, A. Prescott, B. Warne, R. Bousfield, J. P. Skittrall, I. Ramsay, D. Somasunderamb, M. Bevan, J. Coslett, J. Rao, P. Stanley, A. Kennedy, R. Dobson, S. Long, T. Obisanya, T. Esmailji, C. Petridou, K. Saeed, K. Brechany, K. Davis-Blue, H. O’Horan, B. Wakeh, J. Martin, J. Featherstone, C. Hall, J. Allen, G. Johnson, C. Hornigold, N. Amir, K. Henderson, C. McClements, I. Liew, A. Deshpande, E. Vink, D. Trigg, J. Guilfoyle, M. Scarborough, C. Scarborough, T. H. N. Wong, T. Walker, N. Fawcett, G. Morris, K. Tomlin, C. Grix, E. O’Cofaigh, D. McCaffrey, M. Cooper, K. Corbett, K. French, S. Harper, C. Hayward, M. Reid, V. Whatley, J. Winfield, S. Hoque, L. Kelly, I. King, A. Bradley, B. McCullagh, C. Hibberd, M. Merron, C. McCabe, S. Horridge, J. Taylor, S. Koo, F. Elsanousi, R. Saunders, F. Lim, A. Bond, S. Stone, I. D. Milligan, D. J. F. Mack, A. Nagar, R. M. West, M. H. Wilcox, A. Kirby, J. A. T. Sandoe
Abstract
Background: The National Health Service in England advises hospitals collect data on hospital-onset diarrhoea (HOD). Contemporaneous data on HOD are lacking.
Aim: To investigate prevalence, aetiology and management of HOD on medical, surgical and elderly-care wards.
Methods: A cross-sectional study in a volunteer sample of UK hospitals, which collected data on one winter and one summer day in 2016. Patients admitted ≥72 h were screened for HOD (definition: ≥2 episodes of Bristol Stool Type 5-7 the day before the study, with diarrhoea onset >48 h after admission). Data on HOD aetiology and management were collected prospectively.
Findings: Data were collected on 141 wards in 32 hospitals (16 acute, 16 teaching). Point prevalence of HOD was 4.5% (230/5142 patients; 95% confidence interval (CI) 3.9-5.0%). Teaching hospital HOD prevalence (5.9%, 95% CI 5.1-6.9%) was twice that of acute hospitals (2.8%, 95% CI 2.1-3.5%; odds ratio 2.2, 95% CI 1.7-3.0). At least one potential cause was identified in 222/230 patients (97%): 107 (47%) had a relevant underlying condition, 125 (54%) were taking antimicrobials, and 195 (85%) other medication known to cause diarrhoea. Nine of 75 tested patients were Clostridium difficile toxin positive (4%). Eighty (35%) patients had a documented medical assessment of diarrhoea. Documentation of HOD in medical notes correlated with testing for C. difficile (78% of those tested vs 38% not tested, P<0.001). One-hundred and forty-four (63%) patients were not isolated following diarrhoea onset.
Conclusion: HOD is a prevalent symptom affecting thousands of patients across the UK health system each day. Most patients had multiple potential causes of HOD, mainly iatrogenic, but only a third had medical assessment. Most were not tested for C. difficile and were not isolated.
Journal of Hospital Infection 103 (2019) 200-209. doi:10.1016/j.jhin.2019.05.001
PMID: 31077777 - Use of a retrospective methodology to examine the process of care surrounding serious medical events in HIV-positive patients: a feasibility study
Erica R. M. Pool, Vanessa Cooper, Elaney Youssef, Juliet Wright, Jordan Skittrall, Ola Blach, Martin Fisher, Helen Smith
Abstract
Introduction: Comorbidities are increasingly common among people living with HIV (PLWH) as they age. There is no evidence regarding models of care. We aimed to assess feasibility of a novel methodology to investigate care processes for serious medical events in PLWH.
Method: The method was based on the National Confidential Enquiry into Patient Outcome and Death (NCEPOD). Data were extracted from medical records and questionnaires completed by general practitioners (GPs), HIV physicians, and non-HIV specialist physicians. A panel reviewed anonymized cases and gave feedback on the review process.
Results: Eleven of 13 patients consented to the study. Questionnaires were completed by 64% of HIV physicians, 67% of non-HIV specialist physicians, and 55% of GPs. The independent review panel (IRP) advised improvement in the methodology including data presentation and timing.
Conclusion: This method was acceptable to patients and secondary care physicians. Further work is needed to the improve GP responses and facilitate IRP.
Journal of the International Association of Providers of AIDS Care (2019) 18. doi:10.1177/2325958219868747
PMID: 31480913 - A new method for detecting signal regions in ordered sequences of real numbers, and application to viral genomic data
Julia R. Gog, Andrew M. L. Lever, Jordan P. Skittrall
Abstract
We present a fast, robust and parsimonious approach to detecting signals in an ordered sequence of numbers. Our motivation is in seeking a suitable method to take a sequence of scores corresponding to properties of positions in virus genomes, and find outlying regions of low scores. Suitable statistical methods without using complex models or making many assumptions are surprisingly lacking. We resolve this by developing a method that detects regions of low score within sequences of real numbers. The method makes no assumptions a priori about the length of such a region; it gives the explicit location of the region and scores it statistically. It does not use detailed mechanistic models so the method is fast and will be useful in a wide range of applications. We present our approach in detail, and test it on simulated sequences. We show that it is robust to a wide range of signal morphologies, and that it is able to capture multiple signals in the same sequence. Finally we apply it to viral genomic data to identify regions of evolutionary conservation within influenza and rotavirus.
PLoS ONE 13(4): e0195763. doi:10.1371/journal.pone.0195763
PMID: 29652903 - The changing face of bacteraemia in an HIV-1 positive cohort in the United Kingdom
Aliya Bryce, Jordan P. Skittrall, Yvonne Gilleece, Catherine Sargent
Journal of Infection, 2017 74(3)325-328. doi:10.1016/j.jinf.2016.12.014
PMID: 28077282 - An ageing population and changing UK bacteraemia profile may affect the characteristics and microbiology of infective spondylodiscitis
Joseph Donovan, Jordan P. Skittrall, Thomas Moore, Catherine Sargent, Daniel Agranoff, Martin Llewelyn
Journal of Infection, 2016 Jul;73(1):91-3. doi:10.1016/j.jinf.2016.04.005
PMID: 27066877 - Rigid sigmoidoscopy: no contamination of the sigmoidoscopist's face with faecal flora in a small study
J.P. Skittrall, L. Eid-Arimoku, M. Joshi, M.J. Newport, E.M. Moore
Journal of Hospital Infection, 93(1)112-113. doi:10.1016/j.jhin.2016.01.017
PMID: 26996086 - Drug Reaction, Eosinophilia and Systemic Symptoms (DRESS) syndrome secondary to allopurinol with early lymphadenopathy and symptom relapse
Rhiannon Turney, Jordan Peter Skittrall, Joseph Donovan, Daniel Agranoff
Abstract
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare condition with a mortality rate of up to 10%. Herein, we describe a case of DRESS syndrome secondary to allopurinol and which may have been precipitated by amoxicillin, the diagnostic challenge it represented and the successful treatment of the condition with corticosteroids.
BMJ Case Reports, published online 6th October 2015. doi:10.1136/bcr-2015-211222
PMID: 26438678 - Gluon-initiated production of a Kaluza-Klein gluon in a Bulk Randall-Sundrum model
B.C. Allanach, F. Mahmoudi, J.P. Skittrall, K. Sridhar
Abstract
In the Bulk Randall-Sundrum model, the Kaluza-Klein excitations of the gauge bosons are the primary signatures. In particular, the search for the Kaluza-Klein (KK) excitation of the gluon at hadron colliders is of great importance in testing this model. At the leading order in QCD, the production of this KK-gluon proceeds only via q qbar-initial states. We study the production of KK-gluons from gluon initial states at next-to-leading order in QCD. We find that, even after including the sub-dominant KK-gluon loops at this order, the next-to-leading order (NLO) cross-section is tiny compared to the leading order cross-section and unlikely to impact the searches for this resonance at hadron colliders.
SPIRES entry
Published as JHEP 1003:014,2010
arXiv:0910.1350 (mirrors: au br cn de es fr il in it jp kr ru tw uk za aps lanl) - Production of a Z boson and a photon via a Randall-Sundrum-type graviton at the Large Hadron Collider
Jordan P. Skittrall
Abstract
Abstract: In extra dimensional models with Kaluza-Klein graviton states that are well separated in mass, such states may be observed as resonances in collider experiments. We extend previous works on such scenarios by considering the one-loop resonant production of a Z boson in association with a photon. We find the production rate to be negligible in conservative scenarios, and sufficiently small for observation to be very difficult even for reasonable luminosity in less conservative scenarios.
SPIRES entry
Published as Eur. Phys. J. C 60, 291-295 (2009)
arXiv:0809.4383 (mirrors: au br cn de es fr il in it jp kr ru tw uk za aps lanl)
DAMTP-2008-87 - Z boson decay to photon plus Kaluza-Klein graviton: large extra dimensional bounds
Benjamin C. Allanach and Jordan P. Skittrall
Abstract
Abstract: We consider the phenomenology of the decay of a Z boson into a photon and a Kaluza-Klein excitation of the graviton in the ADD model. Using LEP data, we obtain an upper bound on the branching ratio corresponding to this process of ~10-11. This bound would be useful for model discrimination in the event of such a signal at a future collider. We also investigate energy profiles of the process, showing that with sufficient data this process could distinguish between numbers of extra dimensions in the event of discovery of a toroidally-compactified ADD model.
SPIRES entry
Published as Eur. Phys. J. C 55, 107-112 (2008)
arXiv:0709.2929 (mirrors: au br cn de es fr il in it jp kr ru tw uk za aps lanl)
DAMTP-2007-87 - Z boson decay to photon plus Kaluza-Klein graviton in large extra dimensions
Benjamin C. Allanach, Jordan P. Skittrall and K. Sridhar
Abstract
Abstract: In the large extra dimensional ADD scenario, Z bosons undergo a one-loop decay into a photon and Kaluza-Klein towers of gravitons/gravi-scalars. We calculate such a decay width, extending previous arguments about the general form of the four-dimensional on-shell amplitude. The amplitudes calculated are relevant to processes in other extra dimensional models where the Standard Model fields are confined to a 4-brane.
SPIRES entry
Published as JHEP11(2007)089
arXiv:0705.1953 (mirrors: au br cn de es fr il in it jp kr ru tw uk za aps lanl)
DAMTP-2007-42
TIFR/TH/07-08
Teaching and Supervisions
Lecturing
- Natural Sciences Tripos Part II Virology: I give the antivirals lecture in the Part II Virology course.
- Medical Sciences and Veterinary Sciences Tripos Part IA Foundations of Evidence-Based Practice: I have guest lectured on applications of screening in the Foundations of Evidence-Based Practice course.
Undergraduate supervision
I co-ordinate Natural Sciences Tripos Part IA Mathematical Biology teaching for Trinity College. In addition to supervising that course, I supervise the Natural Sciences Tripos Mathematics courses.
Prospective students
I am unable to take PhD students at present, although prospective students who have identified a suitable supervisor and who may have interests that overlap with my research areas are welcome to contact me. University of Cambridge students wishing to undertake shorter projects with me, and clinical academics looking for academic placement opportunities, are very welcome to make contact to discuss possible options.