Imperial College London

Dr. Elita Jauneikaite

Faculty of MedicineSchool of Public Health

Advanced Research Fellow
 
 
 
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e.jauneikaite

 
 
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UG5Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

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Year
to

55 results found

Imai N, Gaythorpe K, Bhatia S, Mangal T, Cuomo-Dannenburg G, Unwin H, Jauneikaite E, Ferguson NMet al., 2022, COVID-19 in Japan, January – March 2020: insights from the first three months of the epidemic, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334

Background:Understanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data. Methods:We conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs. Results:The corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ±2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95%CrI:1.6, 3.3) nationally. In the final week of the trusted period (16 – 23 March 2020), Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6) respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age with individuals more likely to infect, and be infected by, contacts in a similar age group to them. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients <20 years old developing pneumonia or severe respiratory symptoms.Conclusions:Information collected in the early phases of an out

Journal article

Cordery R, Purba AK, Begum L, Mills E, Mosavie M, Vieira A, Jauneikaite E, Leung RCY, Siggins MK, Ready D, Hoffman P, Lamagni T, Sriskandan Set al., 2022, Frequency of transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes in schoolchildren exposed to scarlet fever: a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in England, UK., Lancet Microbe, Vol: 3, Pages: e366-e375

BACKGROUND: Despite recommendations regarding prompt treatment of cases and enhanced hygiene measures, scarlet fever outbreaks increased in England between 2014 and 2018. We aimed to assess the effects of standard interventions on transmission of Streptococcus pyogenes to classroom contacts, households, and classroom environments to inform future guidance. METHODS: We did a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in six settings across five schools in Greater London, UK. Schools and nurseries were eligible to participate if they had reported two cases of scarlet fever within 10 days of each other among children aged 2-8 years from the same class, with the most recent case arising in the preceding 48 h. We cultured throat swabs from children with scarlet fever, classroom contacts, and household contacts at four timepoints. We also cultured hand swabs and cough plates from all cases in years 1 and 2 of the study, and from classroom contacts in year 2. Surface swabs from toys and other fomites in classrooms were cultured in year 1, and settle plates from classrooms were collected in year 2. Any sample with S pyogenes detected was recorded as positive and underwent emm genotyping and genome sequencing to compare with the outbreak strain. FINDINGS: Six classes, comprising 12 cases of scarlet fever, 17 household contacts, and 278 classroom contacts were recruited between March 1 and May 31, 2018 (year 1), and between March 1 and May 31, 2019 (year 2). Asymptomatic throat carriage of the outbreak strains increased from 11 (10%) of 115 swabbed children in week 1, to 34 (27%) of 126 in week 2, to 26 (24%) of 108 in week 3, and then five (14%) of 35 in week 4. Compared with carriage of outbreak S pyogenes strains, colonisation with non-outbreak and non-genotyped S pyogenes strains occurred in two (2%) of 115 swabbed children in week 1, five (4%) of 126 in week 2, six (6%) of 108 in week 3, and in none of the 35 children in week

Journal article

Taylor E, Jauneikaite E, Sriskandan S, Woodford N, Hopkins KLet al., 2022, Novel 16S rRNA methyltransferase RmtE3 in acinetobacter baumannii ST79., Journal of Medical Microbiology, Vol: 71, ISSN: 0022-2615

Introduction. The 16S rRNA methyltransferase (16S RMTase) gene armA is the most common mechanism conferring high-level aminoglycoside resistance in Acinetobacter baumannii, although rmtA, rmtB, rmtC, rmtD and rmtE have also been reported.Hypothesis/Gap statement. The occurrence of 16S RMTase genes in A. baumannii in the UK and Republic of Ireland is currently unknown.Aim. To identify the occurrence of 16S RMTase genes in A. baumannii isolates from the UK and the Republic of Ireland between 2004 and 2015.Methodology. Five hundred and fifty pan-aminoglycoside-resistant A. baumannii isolates isolated from the UK and the Republic of Ireland between 2004 and 2015 were screened by PCR to detect known 16S RMTase genes, and then whole-genome sequencing was conducted to screen for novel 16S RMTase genes.Results. A total of 96.5 % (531/550) of isolates were positive for 16S RMTase genes, with all but 1 harbouring armA (99.8 %, 530/531). The remaining isolates harboured rmtE3, a new rmtE variant. Most (89.2 %, 473/530) armA-positive isolates belonged to international clone II (ST2), and the rmtE3-positive isolate belonged to ST79. rmtE3 shared a similar genetic environment to rmtE2 but lacked an ISCR20 element found upstream of rmtE2.Conclusion. This is the first report of rmtE in A. baumannii in Europe; the potential for transmission of rmtE3 to other bacterial species requires further research.

Journal article

Ledda A, Cummins M, Shaw LP, Jauneikaite E, Cole K, Lasalle F, Barry D, Turton J, Rosmarin C, Anaraki S, Wareham D, Stoesser N, Paul J, Manuel R, Cherian BP, Didelot Xet al., 2022, Hospital outbreak of carbapenem-resistant Enterobacterales associated with a bla OXA-48 plasmid carried mostly by Escherichia coli ST399, Microbial Genomics, Vol: 8, ISSN: 2057-5858

A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous blaOXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399 accounted for 35 of all the 55 isolates. Comparative genomics analysis using publicly available E. coli ST399 genomes showed that the outbreak E. coli ST399 isolates formed a unique clade. We developed a mathematical model of pOXA-48-like plasmid transmission between host lineages and used it to estimate its conjugation rate, giving a lower bound of 0.23 conjugation events per lineage per year. Our analysis suggests that co-evolution between the pOXA-48-like plasmid and E. coli ST399 could have played a role in the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying blaOXA-48 as the main cause of a plasmid-borne outbreak within a hospital setting. Our findings suggest complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.

Journal article

Khan U, Jauneikaite E, Andrews R, Chalker V, Owen Set al., 2022, Identifying large-scale recombination and capsular switching events in Streptococcus agalactiae strains causing disease in adults in the United Kingdom between 2014 and 2015, Microbial Genomics, Vol: 8, ISSN: 2057-5858

Cases of invasive Group B Streptococcal infections in the adult UK population have steadily increased over recent years, with most common serotypes being V, III and Ia, but less is known of the genetic background of these strains. We have carried out in-depth analysis of whole genome sequences of 193 clinically important GBS isolates (186 were from invasive and 7 were from non-invasive infection) isolated from adults and submitted to the National Reference Laboratory at UK Health Security Agency between January 2014 and December 2015. We have determined that capsular serotypes III (26.8%), Ia (26.2%) and V (14.9%) were most commonly identified, with slight differences in gender and age distribution. Most isolates (n=185) grouped to 5 clonal complexes: CC1, CC8, CC17, CC19 and CC23 with common associations between specific serotypes and virulence genes. Additionally, we have identified large recombination events mediating potential capsular switching events between ST1 serotype V and serotypes Ib (n=2 isolates), II (n=2 isolates) and VI (n=2 isolates); ST19 serotype III and serotype V (n=5 isolates); CC17 serotype III and serotype IV (n=1 isolate).The high genetic diversity of disease-causing isolates and multiple recombination events reported in this study, highlight the need for routine surveillance of the circulating disease-causing GBS strains. This information is crucial to better understand global spread of GBS serotypes and genotypes and will form the baseline information for any future GBS vaccine research in the UK and worldwide. Impact statementThis study is the first study to report on in-depth genomic analysis of the disease-causing GBS in adult population in the UK. We describe the most common serotype-genotype combinations, including multi-locus sequence types (MLST) and major virulence gene combinations for the specific serotypes, found in our dataset. Importantly, we report on various potential capsular type switching caused by recombination events fo

Journal article

Jauneikaite E, Honeyford K, Blandy O, Mosavie M, Pearson M, Ramzan FA, Ellington MJ, Parkhill J, Costelloe CE, Woodford N, Sriskandan Set al., 2022, Bacterial genotypic and patient risk factors for adverse outcomes in Escherichia coli bloodstream infections: a prospective molecular epidemiological study, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 77, Pages: 1753-1761, ISSN: 0305-7453

Journal article

Taylor E, Jauneikaite E, Sriskandan S, Woodford N, Hopkins Ket al., 2022, Detection and characterisation of 16S rRNA methyltransferase-producing Pseudomonas aeruginosa from the UK and Republic of Ireland from 2003-2015, International Journal of Antimicrobial Agents, Vol: 59, ISSN: 0924-8579

16S rRNA methyltransferase (16S RMTase) genes confer high-level aminoglycoside resistance, reducing treatment options for multidrug-resistant Gram-negative bacteria. Pseudomonas aeruginosa isolates (n = 221) exhibiting high-level pan-aminoglycoside resistance (amikacin, gentamicin and tobramycin MICs ≥64, ≥32 and ≥32 mg/L, respectively) were screened for 16S RMTase genes to determine their occurrence among isolates submitted to a national reference laboratory from December 2003 to December 2015. 16S RMTase genes were identified using two multiplex PCRs, and whole-genome sequencing (WGS) was used to identify other antibiotic resistance genes, sequence types (STs) and the genetic environment of 16S RMTase genes. 16S RMTase genes were found in 8.6% (19/221) of isolates, with rmtB4 (47.4%; 9/19) being most common, followed by rmtD3 (21.1%; 4/19), rmtF2 (15.8%; 3/19) and single isolates harbouring rmtB1, rmtC and rmtD1. Carbapenemase genes were found in 89.5% (17/19) of 16S RMTase-positive isolates, with blaVIM (52.9%; 9/17) being most common. 16S RMTase genes were found in ‘high-risk’ clones known to harbour carbapenemase genes (ST233, ST277, ST357, ST654 and ST773). Analysis of the genetic environment of 16S RMTase genes identified that IS6100 was genetically linked to rmtB1; IS91 to rmtB4, rmtC or rmtD3; ISCR14 to rmtD1; and rmtF2 was linked to Tn3, IS91 or Tn1721. Although 16S RMTase genes explained only 8.6% of pan-aminoglycoside resistance in the P. aeruginosa isolates studied, the association of 16S RMTase genes with carbapenemase-producers and ‘high-risk’ clones highlights that continued surveillance is required to monitor spread as well as the importance of suppressing the emergence of dually-resistant clones in hospital settings.

Journal article

Myall A, Peach R, Wan Y, Mookerjee S, Jauneikaite E, Bolt F, Price J, Davies F, Weisse A, Holmes AH, Barahona Met al., 2022, Improved contact tracing using network analysis and spatial-temporal proximity, IMED conference, Publisher: ELSEVIER SCI LTD, Pages: S20-S20, ISSN: 1201-9712

Conference paper

Imai N, Gaythorpe KAM, Bhatia S, Mangal TD, Cuomo-Dannenburg G, Unwin HJT, Jauneikaite E, Ferguson NMet al., 2022, COVID-19 in Japan: insights from the first three months of the epidemic, Publisher: Cold Spring Harbor Laboratory

BackgroundUnderstanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data. MethodsWe conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs. ResultsThe corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ±2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95%CrI:1.6, 3.3) nationally. In the final week of the trusted period, Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6) respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients &lt;20 years old developing pneumonia or severe respiratory symptoms.ConclusionsInformation collected in the early phases of an outbreak are important in characterising any novel pathogen. Timely recognition of key symptoms and high-risk settings for transmi

Working paper

Aliabadi S, Jauneikaite E, Muller-Pebody B, Hope R, Vihta K-D, Horner C, Costelloe CEet al., 2021, Exploring temporal trends and risk factors for resistance in Escherichia coli-causing bacteraemia in England between 2013 and 2018: an ecological study, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 77, Pages: 782-792, ISSN: 0305-7453

Journal article

Wan Y, Mills E, Leung RCY, Vieira A, Zhi X, Croucher NJ, Woodford N, Jauneikaite E, Ellington MJ, Sriskandan Set al., 2021, Alterations in chromosomal genes nfsA, nfsB, and ribE are associated with nitrofurantoin resistance in escherichia coli from the UK, Microbial Genomics, Vol: 7, Pages: 1-19, ISSN: 2057-5858

Antimicrobial resistance in enteric or urinary Escherichia coli is a risk factor for invasive E. coli infections. Due to widespread trimethoprim resistance amongst urinary E. coli and increased bacteraemia incidence, a national recommendation to prescribe nitrofurantoin for uncomplicated urinary tract infection was made in 2014. Nitrofurantoin resistance is reported in <6% urinary E. coli isolates in the UK, however, mechanisms underpinning nitrofurantoin resistance in these isolates remain unknown. This study aimed to identify the genetic basis of nitrofurantoin resistance in urinary E. coli isolates collected from north west London and then elucidate resistance-associated genetic alterations in available UK E. coli genomes. As a result, an algorithm was developed to predict nitrofurantoin susceptibility.Deleterious mutations and gene-inactivating insertion sequences in chromosomal nitroreductase genes nfsA and/or nfsB were identified in genomes of nine nitrofurantoin-resistant urinary E. coli isolates, as well as all further 11 E. coli isolates that were experimentally validated to be nitrofurantoin resistant. Eight categories of allelic changes in nfsA, nfsB, and the associated gene ribE were detected in 12,412 E. coli genomes from the UK. Evolutionary analysis of these three genes revealed homoplasic mutations and explained the previously reported order of stepwise mutations. The mobile gene complex oqxAB, which is associated with reduced nitrofurantoin susceptibility, was identified in only one of the 12,412 genomes.In conclusion, mutations and insertion sequences in nfsA and nfsB were leading causes of nitrofurantoin resistance in UK E. coli. As nitrofurantoin exposure increases in human populations, the prevalence of nitrofurantoin resistance in carriage E. coli isolates and those from urinary and bloodstream infections should be monitored.

Journal article

Aliabadi S, Anyanwu P, Beech E, Jauneikaite E, Wilson P, Hope R, Majeed A, Muller-Pebody B, Costelloe, Costelloe Cet al., 2021, Do antibiotic stewardship interventions in primary care have an effect on antimicrobial resistance of Escherichia coli bacteraemia in England? An ecological analysis of national data between 2013-2018, The Lancet Infectious Diseases, Vol: 21, ISSN: 1473-3099

Background: We sought to evaluate the effectiveness of a national antimicrobial stewardship intervention, the Quality Premium (QP), on broad-spectrum antibiotic prescribing and Escherichia coli bacteraemia resistance to broad-spectrum antibiotics in England. Methods: We used longitudinal data on patients registered with a general practitioner in the English National Health Service and patients with E. coli bacteraemia notified to the national mandatory surveillance programme between January 2013-December 2018.We conducted an ecological analysis using interrupted time series (ITS) analyses and generalised estimating equations (GEE) to estimate the change in broad-spectrum antibiotics prescribing over time and change in the proportion of E. coli bacteraemia cases where the causative bacteria were resistant to each antibiotic individually or to at least one of the five antibiotics, after implementation of the QP. Findings: Following the implementation of the QP in April 2015, we observed an immediate downward step-change in broad-spectrum antibiotic prescribing incidence rate of 0.867per 1000 patients (95% CI: 0.837 to 0.898, p<0·001). We found that the pre-intervention slope for total antibiotic usage was an IRR of 1.002(CI: 1.000to 1.004, p-value=0.046). The change in slope for total antibiotic usage was an IRR of 0.993(CI: 0.991to 0.995, p<0·001). We also observed a downward step-change in resistance rate of 0.947 per 1000 E. coli isolates tested (95% CI: 0.918 to 0.977, p<0·001).We found that the pre-intervention slope for total antibiotic resistance was an IRR of 1.001 (CI: 0.999 to 1.003, p-value=0.346). The change in slope level for total antibiotic usage was an IRR of 0.999 (CI: 0.997 to 1.000, p=0.112). On examination of the long-term effect following implementation of the QP, there was an increase in the number of isolates resistant to at least one of the five broad-spectrum antibiotics tested.134Interpretati

Journal article

Cordery R, Purba A, Begum L, Mills E, Mosavie M, Vieira A, Jauneikaite E, Leung RCY, Siggins M, Ready D, Hoffman P, Lamagni T, Sriskandan Set al., 2021, Frequency of Transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes among school children exposed to scarlet fever: a longitudinal multi-cohort molecular epidemiology contact tracing study, The Lancet Microbe, ISSN: 2666-5247

Background: Despite recommendations regarding prompt treatment of cases and enhanced hygiene measures, scarlet fever outbreaks increased in England between 2014-2018. Methods: We undertook a prospective, intensive contact tracing study in schools with consecutive scarlet fever cases to assess the impact of standard interventions on transmission of Streptococcus pyogenes between cases, classroom contacts, households, and classroom environments over 4 weeks using genome sequencing. Findings: Six classes, comprising 12 scarlet fever cases, 17 household contacts, and 278 classroom contacts were recruited. Prevalence of the outbreak strain in asymptomatic classroom contacts was high, increasing from 9.6% in week 1, to 26.9% in week 2, 23.9% in week 3, then 14.3% in week 4. Colonisation with non-outbreak strains was 0 - 7.5%. Genome sequencing showed clonality of isolates within each of six classes, confirming recent transmission accounted for high carriage. Of asymptomatic classroom contacts with S. pyogenes -positive throat swabs who were tested for transmissibility, 6/28 (21%) had positive cough plates and/or hand swabs, of whom three remained S. pyogenes -positive for 3 weeks. Only 1/60 surface swabs taken in 3 classrooms yielded S. pyogenes . In contrast, settle plates placed in elevated locations were S. pyogenes -positive in both classrooms tested. Interpretation: S. pyogenes transmission in schools is intense and may occur prior to, or in spite of reported treatment of cases, underlining a need for rapid case management. Despite guideline adherence, heavy shedding of S. pyogenes by small numbers of classroom contacts may perpetuate outbreaks, and airborne transmission has a plausible role in spread. Funding: Action Medical Research, UKRI, NIHR

Journal article

Boonyasiri A, Myall AC, Wan Y, Bolt F, Ledda A, Mookerjee S, Weiße AY, Turton JF, Abbas H, Prakapaite R, Sabnis A, Abdolrasouli A, Malpartida-Cardenas K, Miglietta L, Donaldson H, Gilchrist M, Hopkins KL, Ellington MJ, Otter JA, Larrouy-Maumus G, Edwards AM, Rodriguez-Manzano J, Didelot X, Barahona M, Holmes AH, Jauneikaite E, Davies Fet al., 2021, Integrated patient network and genomic plasmid analysis reveal a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both <i>bla</i><sub>IMP</sub> and <i>mcr-9</i> genes

<jats:title>Abstract</jats:title><jats:p>The incidence of carbapenemase-producing Enterobacterales (CPE) is rising globally, yet Imipenemase (IMP) carbapenemases remain relatively rare. This study describes an investigation of the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network.</jats:p><jats:p>A network analysis approach to patient pathways, using routinely collected electronic health records, identified previously unrecognised contacts between patients who were IMP CPE positive on screening, implying potential bacterial transmission events. Whole genome sequencing of 85 Enterobacterales isolates from these patients revealed that 86% (73/85) were diverse species (predominantly <jats:italic>Klebsiella</jats:italic> spp, <jats:italic>Enterobacter</jats:italic> spp, <jats:italic>E. coli</jats:italic>) and harboured an IncHI2 plasmid, which carried both <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub> and the putative mobile colistin resistance gene <jats:italic>mcr-9</jats:italic>. Detailed phylogenetic analysis identified two distinct IncHI2 plasmid lineages, A and B, both of which showed significant association with patient movements between four hospital sites and across medical specialities.</jats:p><jats:p>Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub>CPE, which remained unidentified during standard microbiology and infection control investigations. With whole genome sequencing (WGS) technologies and large-data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Analysing outbreaks at the plasmid level reveal

Journal article

To K-N, Powell O, Jamrozy D, Kopunova R, Anastasiadou K, Faal A, Secka O, Chalker V, Le Doare K, Jauneikaite Eet al., 2021, RAPD PCR detects co-colonisation of multiple Group B Streptococcus genotypes: a practical molecular technique for screening multiple colonies, Journal of Microbiological Methods, Vol: 190, ISSN: 0167-7012

Group B Streptococcus (GBS) is a leading cause of neonatal meningitis, pneumonia, and sepsis. The biggest contributing factor of neonatal infections is due to vertical transmission from maternal colonisation of GBS in the genitourinary tract. Multiple serotype colonisation is often not investigated in epidemiological studies, but it is an important consideration for serotype-based vaccine development and implementation to ensure less abundant serotypes are not under-represented. In this study, we show that RAPD PCR is a quick tool useful in screening the presence of genetically different strains using multiple colony picks from a single patient swab. We observed a maximum of five different GBS strains colonising a single patient at a specific time.

Journal article

Miglietta L, Moniri A, Pennisi I, Malpartida-Cardenas K, Abbas H, Hill-Cawthorne K, Bolt F, Jauneikaite E, Davies F, Holmes A, Georgiou P, Rodriguez Manzano Jet al., 2021, Coupling machine learning and high throughput multiplex digital PCR enables accurate detection of carbapenem-resistant genes in clinical isolates, Frontiers in Molecular Biosciences, Vol: 8, Pages: 1-11, ISSN: 2296-889X

Rapid and accurate identification of patients colonised with carbapenemase-producing organisms (CPOs) is essential to adopt prompt prevention measures to reduce the risk of transmission. Recent studies have demonstrated the ability to combine machine learning (ML) algorithms with real-time digital PCR (dPCR) instruments to increase classification accuracy of multiplex PCR assays when using synthetic DNA templates. We sought to determine if this novel methodology could be applied to improve identification of the five major carbapenem-resistant genes in clinical CPO-isolates, which would represent a leap forward in the use of PCR-based data-driven diagnostics for clinical applications. We collected 3 clinical isolates (including 221 CPO-positive samples) and developed a novel 5-plex PCR assay for detection of blaIMP, blaKPC, blaNDM, blaOXA-48 and blaVIM. Combining the recently reported ML method ‘Amplification and Melting Curve Analysis’ (AMCA) with the abovementioned multiplex assay, we assessed the performance of the AMCA methodology in detecting these genes. The improved classification accuracy of AMCA relies on the usage of real-time data from a single fluorescent channel and benefits from the kinetic/thermodynamic information encoded in the thousands of amplification events produced by high throughput real-time dPCR. The 5-plex showed a lower limit of detection of 10 DNA copies per reaction for each primer set and no cross-reactivity with other carbapenemase genes. The AMCA classifier demonstrated excellentpredictive performance with 99.6% (CI 97.8-99.9%) accuracy (only one misclassified sample out of the 253, with a total of 160,041 positive amplification events), which represents a 7.9% increase (p value < 0.05) compared to conventional melting curve analysis. This work demonstrates the use of the AMCA method to increase the throughput and performance of state-of-the-art molecular diagnostic platforms, without hardware modifications and additiona

Journal article

Jauneikaite E, Pichon B, Mosavie M, Fallowfield JL, Davey T, Thorpe N, Nelstrop A, Sriskandan S, Lamb LEet al., 2021, Staphylococcus argenteus transmission among healthy Royal Marines: a molecular epidemiology case-study, Journal of Infection, Vol: 83, ISSN: 0163-4453

Objectives: During a prospective study of S. aureus carriage in Royal Marines recruits, six S. argenteus strains were identified in four recruits. As S. argenteus sepsis leads to mortality similar to S. aureus, we determined the potential for within same troop transmission, to evaluate future outbreak risk.Methods: We used whole-genome sequencing to characterise S. argenteus and investigate phylogenetic relationships between isolates.Results: S. argenteus strains (t5078, ST2250) were detected in 4/40 recruits in the same troop (training cohort) in weeks 1, 6 or 15 of training. No mec, tsst or LukPV genes were detected. We identified differences of 1-17 core SNPs between S. argenteus from different recruits. In two recruits, two S. argenteus strains were isolated; these could be distinguished by 2 and 15 core SNPs.Conclusions: The identification of S. argenteus within a single troop from the total recruit population suggests a common source for transmission, though high number of SNPs were identified, both within-host and within-cluster. The high number of SNPs between some isolates may indicate a common source of diverse isolates or a high level of S. argenteus mutation in carriage. S. argenteus is newly recognised species; and understanding of the frequency of genetic changes during transmission and transition from asymptomatic carriage to disease is required.

Journal article

Bhatia S, Parag K, Wardle J, Imai N, Elsland SV, Lassmann B, Cuomo-Dannenburg G, Jauneikaite E, Unwin HJ, Riley S, Ferguson N, Donnelly C, Cori A, Nouvellet Pet al., 2021, Global predictions of short- to medium-term COVID-19 transmission trends : a retrospective assessment

<jats:title>Abstract</jats:title> <jats:p>From 8th March to 29th November 2020, we produced weekly estimates of SARS-CoV-2 transmissibility and forecasts of deaths due to COVID-19 for 81 countries with evidence of sustained transmission. We also developed a novel heuristic to combine weekly estimates of transmissibility to produce forecasts over a 4-week horizon. We evaluated the robustness of the forecasts using relative error, coverage probability, and comparisons with null models. During the 39-week period covered by this study, both the short- and medium-term forecasts captured well the epidemic trajectory across different waves of COVID-19 infections with small relative errors over the forecast horizon. The model was well calibrated with 56.3\% and 45.6\% of the observations lying in the 50\% Credible Interval in 1-week and 4-week ahead forecasts respectively. We could accurately characterise the overall phase of the epidemic up to 4-weeks ahead in 84.9\% of country-days. The medium-term forecasts can be used in conjunction with the short-term forecasts of COVID-19 mortality as a useful planning tool as countries continue to relax public health measures.</jats:p>

Journal article

Aliabadi S, Anyanwu P, Beech E, Jauneikaite E, Wilson P, Hope R, Majeed A, Muller-Pebody B, Costelloe Cet al., 2021, Effect of antibiotic stewardship interventions in primary care on antimicrobial resistance of Escherichia coli bacteraemia in England (2013-18): a quasi-experimental, ecological, data linkage study, Lancet Infectious Diseases, Vol: 21, ISSN: 1473-3099

BACKGROUND: Antimicrobial resistance is a major global health concern, driven by overuse of antibiotics. We aimed to assess the effectiveness of a national antimicrobial stewardship intervention, the National Health Service (NHS) England Quality Premium implemented in 2015-16, on broad-spectrum antibiotic prescribing and Escherichia coli bacteraemia resistance to broad-spectrum antibiotics in England. METHODS: In this quasi-experimental, ecological, data linkage study, we used longitudinal data on bacteraemia for patients registered with a general practitioner in the English National Health Service and patients with E coli bacteraemia notified to the national mandatory surveillance programme between Jan 1, 2013, and Dec 31, 2018. We linked these data to data on antimicrobial susceptibility testing of E coli from Public Health England's Second-Generation Surveillance System. We did an ecological analysis using interrupted time-series analyses and generalised estimating equations to estimate the change in broad-spectrum antibiotics prescribing over time and the change in the proportion of E coli bacteraemia cases for which the causative bacteria were resistant to each antibiotic individually or to at least one of five broad-spectrum antibiotics (co-amoxiclav, ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin), after implementation of the NHS England Quality Premium intervention in April, 2015. FINDINGS: Before implementation of the Quality Premium, the rate of antibiotic prescribing for all five broad-spectrum antibiotics was increasing at rate of 0·2% per month (incidence rate ratio [IRR] 1·002 [95% CI 1·000-1·004], p=0·046). After implementation of the Quality Premium, an immediate reduction in total broad-spectrum antibiotic prescribing rate was observed (IRR 0·867 [95% CI 0·837-0·898], p<0·0001). This effect was sustained until the end of the study period; a 57% reduction in rate of antibiotic pr

Journal article

Knock ES, Whittles LK, Lees JA, Perez-Guzman PN, Verity R, FitzJohn RG, Gaythorpe KAM, Imai N, Hinsley W, Okell LC, Rosello A, Kantas N, Walters CE, Bhatia S, Watson OJ, Whittaker C, Cattarino L, Boonyasiri A, Djaafara BA, Fraser K, Fu H, Wang H, Xi X, Donnelly CA, Jauneikaite E, Laydon DJ, White PJ, Ghani AC, Ferguson NM, Cori A, Baguelin Met al., 2021, Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England, Science Translational Medicine, Vol: 13, Pages: 1-12, ISSN: 1946-6234

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission.

Journal article

Gaythorpe K, Bhatia S, Mangal T, Unwin H, Imai N, Cuomo-Dannenburg G, Walters C, Jauneikaite E, Bayley H, Kont M, Mousa A, Whittles L, Riley S, Ferguson Net al., 2021, Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility, Scientific Reports, Vol: 11, Pages: 1-14, ISSN: 2045-2322

Background: SARS-CoV-2 infections have been reported in all age groups including infants, children, and adolescents. However, the role of children in the COVID-19 pandemic is still uncertain. This systematic review of early studies synthesises evidence on the susceptibility of children to SARS-CoV-2 infection, the severity and clinical outcomes in children with SARS-CoV-2 infection, and the transmissibility of SARS-CoV-2 by children in the early phases of the COVID-19 pandemic. Methods and findings: A systematic literature review was conducted in PubMed. Reviewers extracted data from relevant, peer-reviewed studies published up to July 4th 2020 during the first wave of the SARS-CoV-2 outbreak using a standardised form and assessed quality using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. For studies included in the meta-analysis, we used a random effects model to calculate pooled estimates of the proportion of children considered asymptomatic or in a severe or critical state. We identified 2,775 potential studies of which 128 studies met our inclusion criteria; data were extracted from 99, which were then quality assessed. Finally, 29 studies were considered for the meta-analysis that included information of symptoms and/or severity, these were further assessed based on patient recruitment. Our pooled estimate of the proportion of test positive children who were asymptomatic was 21.1% (95% CI: 14.0 - 28.1%), based on 13 included studies, and the proportion of children with severe or critical symptoms was 3.8% (95% CI: 1.5 - 6.0%), based on 14 included studies. We did not identify any studies designed to assess transmissibility in children and found that susceptibility to infection in children was highly variable across studies.Conclusions: Children’s susceptibility to infection and onward transmissibility relative to adults is still unclear and varied widely between studies. However, it is evident that most children e

Journal article

Jauneikaite E, Honeyford K, Blandy O, Mosavie M, Pearson M, Ramzan FA, Ellington M, PARKHILL J, Costelloe C, Woodford N, Sriskandan Set al., 2021, Bacterial genotypic and patient risk factors for adverse outcomes in Escherichia coli bloodstream infections: a prospective molecular-epidemiological study, Journal of Antimicrobial Chemotherapy, ISSN: 0305-7453

Objectives:Escherichia coli bloodstream infections have shown a sustained increase in England, for reasons that are unknown. Furthermore, the contribution of multi-drug resistant lineages such as ST131 to overall E. coli disease burden and outcome is undetermined. Methods:We genome sequenced E. coli blood isolates from all patients with E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned multi-locus sequence types, virulence factors, and AMR genes to all isolates. Isolate sequence types were then linked to phenotypic antimicrobial susceptibility, patient demographic, and clinical outcome data to explore relationships between the E. coli sequence types, patient factors, and outcomes. Results:A total of 551 E. coli genomes were analysed. Four sequence types (ST131, 21.2%; ST73, 14.5%; ST69, 9.3%; and ST95, 8.2%) accounted for over half of cases. E. coli genotype ST131-C2 was associated with phenotypic non-susceptibility to quinolones, third-generation cephalosporins, amoxicillin, amoxicillin-clavulanic acid, gentamicin, and trimethoprim. Among 300 patients from whom outcome was known, an association between the ST131-C2 lineage and longer length-of-stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli sequence type and mortality. Several unexpected associations were identified between gentamicin non-susceptibility; ethnicity; sex and adverse outcomes, requiring further research.Conclusions:Although E. coli sequence type was associated with defined antimicrobial non-susceptibility patterns and prolonged length-of-stay, E. coli sequence type was not associated with increased mortality. ST131 has outcompeted other lineages in north-west London. Where ST131 is prevalent, caution is required when devising empiric regimens for suspected Gram-negative sepsis, in particular the pairing of beta-lactam agents with gentamicin.

Journal article

Jauneikaite E, Pichon B, Mosavie M, Fallowfield JL, Davey T, Thorpe N, Nelstrop A, Sriskandan S, Lamb LEet al., 2021, Characterisation of <i>Staphylococcus argenteus</i> carried by healthy Royal Marines: a molecular epidemiology case-study

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>During a prospective study of <jats:italic>S. aureus</jats:italic> carriage in Royal Marines (RM) recruits, six <jats:italic>S. argenteus</jats:italic> strains were identified in four recruits undertaking military training together. As <jats:italic>S. argenteus</jats:italic> sepsis leads to mortality similar to <jats:italic>S. aureus</jats:italic>, we determined the potential for person-to-person transmission, to evaluate future outbreak risk.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used whole-genome sequencing to characterise <jats:italic>S. argenteus</jats:italic> and investigate phylogenetic relationships between isolates. Participant colonisation with <jats:italic>S. aureus</jats:italic> and skin and soft tissue infection acquisition were recorded.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>All six <jats:italic>S. argenteus</jats:italic> strains were <jats:italic>spa</jats:italic>-type t5078, ST2250. Strains were detected in 4/40 recruits in the same troop (training cohort) in weeks 1, 6 or 15 of training. No <jats:italic>mec, tsst</jats:italic> or <jats:italic>LukPV</jats:italic> genes were detected. We identified differences of 10-35 core SNPs between <jats:italic>S. argenteus</jats:italic> from different recruits. In two recruits, two <jats:italic>S. argenteus</jats:italic> strains were isolated; these could be distinguished by 3 and 15 core SNPs in each case. <jats:italic>S. argenteus</jats:italic> was not identified in any one of the other 21 participating troops (1,012 recruits).</jats:p></jats:sec><jats:sec><jats:title>Conclusions&

Journal article

Wan Y, Mills E, Leung RCY, Vieira A, Jauneikaite E, Zhi X, Croucher NJ, Woodford N, Ellington MJ, Sriskandan Set al., 2021, Diverse Genetic Determinants of Nitrofurantoin Resistance in UK <i>Escherichia coli</i>

<jats:title>Abstract</jats:title><jats:p>Antimicrobial resistance in enteric or urinary <jats:italic>Escherichia coli</jats:italic> is a risk factor for invasive <jats:italic>E. coli</jats:italic> infections. Due to widespread trimethoprim resistance amongst urinary <jats:italic>E. coli</jats:italic> and increased bacteraemia incidence, a national recommendation to prescribe nitrofurantoin for uncomplicated urinary tract infection was made in 2018. Nitrofurantoin resistance is reported in &lt;6% urinary <jats:italic>E. coli</jats:italic> isolates in the UK. However, mechanisms underpinning nitrofurantoin resistance in these isolates remain unknown. This study aimed to identify genetic determinants of nitrofurantoin resistance in a local <jats:italic>E. coli</jats:italic> collection and assess their prevalence in a larger dataset of <jats:italic>E. coli</jats:italic> genomes. Deleterious point mutations and gene-inactivating insertion sequences in both chromosomal nitroreductase genes <jats:italic>nfsA</jats:italic> and <jats:italic>nfsB</jats:italic> were identified in genomes of nine nitrofurantoin-resistant urinary <jats:italic>E. coli</jats:italic> isolates collected from north west London. Eight types of genetic alterations were identified when comparing sequences of <jats:italic>nfsA</jats:italic>, <jats:italic>nfsB</jats:italic>, and the associated gene <jats:italic>ribE</jats:italic> in 12,412 <jats:italic>E. coli</jats:italic> genomes collected from across the UK. Evolutionary analysis revealed homoplasic mutations and explained the order of stepwise mutations. An algorithm was developed to predict nitrofurantoin susceptibility and predictions for 20 accessible isolates were experimentally validated. Only one genome carrying <jats:italic>oqxAB</jats:italic>, a mobile gene

Journal article

Collin SM, Groves N, O' Sullivan C, Jauneikaite E, Patel D, CUnney R, Meehan M, Reynolds A, Smith A, Lindsay D, Doherty L, Davies E, Chalker V, Lamb P, Afshar B, Balasegaram S, Coelho J, Ready D, Brown CS, Efstratiou A, Le Doare K, Sriskandan S, Heath PT, Lamagni Tet al., 2021, Uncovering infant group B streptococcal (GBS) disease clusters in the UK and Ireland through genomic analysis: a population-based epidemiological study, Clinical Infectious Diseases, Vol: 72, Pages: e296-e302, ISSN: 1058-4838

BackgroundThe true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases.MethodsPotentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7–89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists.ResultsAnalysis of sequences indicated a cutoff of ≤5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically identical pairs with 0 SNP differences, 1 pair with 3 SNP differences, 1 cluster of 4 cases with ≤1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and 1 an early-onset index case. Serial intervals between cases ranged from 0 to 59 (median 12) days.ConclusionsApproximately 1 in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of the clusters were previously undetected, emphasizing the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation.

Journal article

Watson O, Alhaffar M, Mehchy Z, Whittaker C, Akil Z, Brazeau N, Cuomo-Dannenburg G, Hamlet A, Thompson H, Baguelin M, Fitzjohn R, Knock E, Lees J, Whittles L, Mellan T, Winskill P, COVID-19 Response Team IC, Howard N, Clapham H, Checchi F, Ferguson N, Ghani A, Walker P, Beals Eet al., 2021, Leveraging community mortality indicators to infer COVID-19 mortality and transmission dynamics in Damascus, Syria, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported considerably lower mortality rates than in Europe and the Americas. Motivated by reports of an overwhelmed health system, we estimate the likely under-ascertainment of COVID-19 mortality in Damascus, Syria. Using all-cause mortality data, we fit a mathematical model of COVID-19 transmission to reported mortality, estimating that 1.25% of COVID-19 deaths (sensitivity range 1.00% – 3.00%) have been reported as of 2 September 2020. By 2 September, we estimate that 4,380 (95% CI: 3,250 – 5,550) COVID-19 deaths in Damascus may have been missed, with 39.0% (95% CI: 32.5% – 45.0%) of the population in Damascus estimated to have been infected. Accounting for under-ascertainment corroborates reports of exceeded hospital bed capacity and is validated by community-uploaded obituary notifications, which confirm extensive unreported mortality in Damascus.

Journal article

Miglietta L, Moniri A, Pennisi I, Malpartida Cardenas K, Abbas H, Hill-Cawthorne K, Bolt F, Davies F, Holmes AH, Georgiou P, Rodriguez Manzano Jet al., 2021, Coupling machine learning and high throughput multiplex digital PCR enables accurate detection of carbapenem-resistant genes in clinical isolates, Publisher: Cold Spring Harbor Laboratory

<jats:p>Background: The emergence and spread of carbapenemase-producing organisms (CPO) are a significant clinical and public health concern. Rapid and accurate identification of patients colonised with CPO is essential to adopt prompt prevention measures in order to reduce the risk of transmission. Recent proof-of-concept studies have demonstrated the ability to combine machine learning (ML) algorithms with real-time digital PCR (dPCR) instruments to increase classification accuracy of multiplex assays. From this, we sought to determine if this ML based methodology could accurately identify five major carbapenem-resistant genes in clinical CPO-isolates.Methods: We collected 253 clinical isolates (including 221 CPO-positive samples) and developed a novel 5-plex assay for detection of blaVIM, blaOXA-48, blaNDM, blaIMP and blaKPC. Combining the recently reported ML method "Amplification and Melting Curve Analysis" (AMCA) with the abovementioned multiplex assay, we assessed the performance of the methodology in detecting these five carbapenem-resistant genes. The classification accuracy relies on the usage of real-time data from a single fluorescent channel and benefits from the kinetic and thermodynamic information encoded in the thousands of amplification events produced by high throughput dPCR.Results: The 5-plex showed a lower limit of detection of 100 DNA copies per reaction for each primer set and no cross-reactivity with other carbapenemase genes. The AMCA classifier demonstrated excellent predictive performance with 99.6% (CI 97.8-99.9%) accuracy (only one misclassified sample out of the 253, with a total of 163,966 positive amplification events), which represents a 7.9% increase compared to the conventional ML-based melting curve analysis (MCA) method.Conclusion: This work demonstrates the utility of the AMCA method to increase the throughput and performance of state-of-the-art molecular diagnostic platforms, reducing costs without any changes

Working paper

Ragonnet-Cronin M, Boyd O, Geidelberg L, Jorgensen D, Nascimento F, Siveroni I, Johnson R, Baguelin M, Cucunuba Z, Jauneikaite E, Mishra S, Watson O, Ferguson N, Cori A, Donnelly C, Volz Eet al., 2021, Genetic evidence for the association between COVID-19 epidemic severity and timing of non-pharmaceutical interventions, Nature Communications, Vol: 12, Pages: 1-7, ISSN: 2041-1723

Unprecedented public health interventions including travel restrictions and national lockdowns have been implemented to stem the COVID-19 epidemic, but the effectiveness of non- pharmaceutical interventions is still debated. We carried out a phylogenetic analysis of more than 29,000 publicly available whole genome SARS-CoV-2 sequences from 57 locations to estimate the time that the epidemic originated in different places. These estimates were examined in relation to the dates of the most stringent interventions in each location as well as to the number of cumulative COVID-19 deaths and phylodynamic estimates of epidemic size. Here we report that the time elapsed between epidemic origin and maximum intervention is associated with different measures of epidemic severity and explains 11% of the variance in reported deaths one month after the most stringent intervention. Locations where strong non-pharmaceutical interventions were implemented earlier experienced 30 much less severe COVID-19 morbidity and mortality during the period of study.

Journal article

Myall A, Peach RL, Wan Y, Mookerjee S, Jauneikaite E, Bolt F, Price J, Davies F, Weiße AY, Holmes A, Barahona Met al., 2021, Characterising contact in disease outbreaks via a network model of spatial-temporal proximity

<jats:title>ABSTRACT</jats:title><jats:p>Contact tracing is a key tool in epidemiology to identify and control outbreaks of infectious diseases. Existing contact tracing methodologies produce contact maps of individuals based on a binary definition of contact which can be hampered 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 individuals 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.</jats:p>

Journal article

Pi L, Expert P, Clarke JM, Jauneikaite E, Costelloe CEet al., 2021, Electronic health record enabled track and trace in an urban hospital network: implications for infection prevention and control

<jats:title>ABSTRACT</jats:title><jats:p>Healthcare-associated infections represent one of the most significant challenges for modern medicine as they can significantly impact patients’lives. Carbapenemase-producing Enterobacteriaceae (CPE) pose the greatest clinical threat, given the high levels of resistance to carbapenems, which are considered as agents of ‘last resort’ against life-threatening infections. Understanding patterns of CPE infection spreading in hospitals is paramount to design effective infection control protocols to mitigate the presence of CPE in hospitals. We used patient electronic health records from three urban hospitals to: i) track microbiologically confirmed carbapenemase producing <jats:italic>Escherichia coli</jats:italic> (CP-Ec) carriers and ii) trace the patients they shared place and time with until their identification. We show that yearly contact networks in each hospital consistently exhibit a core-periphery structure, highlighting the presence of a core set of wards where most carrier-contact interactions occured before being distributed to peripheral wards. We also identified functional communities of wards from the general patient movement network. The contact networks projected onto the general patient movement community structure showed a comprehensive coverage of the hospital. Our findings highlight that infections such as CP-Ec infections can reach virtually all parts of hospitals through first-level contacts.</jats:p>

Journal article

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