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  • 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., 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

    , The Lancet Microbe, Vol: 3, Pages: e366-e375, ISSN: 2666-5247

    BackgroundDespite 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.MethodsWe 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.FindingsSix 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 4

  • 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
    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
    Charani E, Holmes A, Bonaconsa C, Mbamalu O, Mendelson M, Surendran S, Singh S, Nampoothiri V, Boutall A, Tarrant C, Dhar P, Pennel T, Leather A, Hampton Met al., 2021,

    Investigating infection management and antimicrobial stewardship in surgery: a qualitative study from India and South Africa

    , Clinical Microbiology and Infection, Vol: 27, Pages: 1455-1464, ISSN: 1198-743X

    Objectives To investigate the drivers for infection management and antimicrobial stewardship (AMS) across high infection risk surgical pathways. Methods An qualitative study, ethnographic observation of clinical practices, patient case studies, and face-to-face interviews with healthcare professionals (HCP) and patients was conducted across cardiovascular and thoracic and gastrointestinal surgical pathways in South Africa (SA) and India. Aided by Nvivo 11 software, data were coded and analysed until saturation was reached. The multiple modes of enquiry enabled cross-validation and triangulation of findings.Results Between July 2018–August 2019 data were gathered from 190 hours of non-participant observations (138 India, 72 SA); interviews with HCPs (44 India, 61 SA); patients (6 India, 8 SA), and, case studies (4 India, 2 SA). Across the surgical pathway, multiple barriers impede effective infection management and AMS. The existing, implicit roles of HCPs (including nurses, and senior surgeons) are overlooked as interventions target junior doctors, bypassing the opportunity for integrating infection-related care across the surgical team. Critically, the ownership of decisions remains with the operating surgeons and entrenched hierarchies restrict the inclusion of other HCPs in decision-making. The structural foundations to enable staff to change their behaviours and participate in infection-related surgical care is lacking.ConclusionsIdentifying the implicit existing HCPs roles in infection management is critical and will facilitate the development of effective and transparent processes across the surgical team for optimised care. Applying a framework approach that includes nurse leadership, empowering pharmacists and engaging surgical leads is essential for integrated AMS and infection-related care. Keywords: antibiotic prescribing, infection control, ethnography, low- and middle-income country, surgery

  • Journal article
    Bonaconsa C, Mbamalu O, Mendelson M, Boutall A, Warden C, Rayamajhi S, Pennel T, Hampton M, Joubert I, Tarrant C, Holmes A, Charani Eet al., 2021,

    Visual mapping of team dynamics and communication patterns on surgical ward rounds: an ethnographic study

    , BMJ Quality & Safety, Vol: 30, Pages: 812-824, ISSN: 2044-5415

    Background: Team dynamics influence infection prevention and management practices and implementation of antibiotic stewardship (AS). Using an innovative visual mapping approach, alongside traditional qualitative methods, we aimed to study team dynamics and flow of communication (who gets to speak, and whose voice is heard) during surgical ward rounds, and how team dynamics and communication patterns may shape decision-making in relation to infection management and AS.Materials/methods: Between May and November 2019, data were gathered through direct observations of ward rounds and face-to-face interviews with ward round participants in selected surgical specialties at a tertiary hospital in South Africa. Using a visual mapping method – sociograms – content and flow of communication and the social links between individual participants were plotted. Field notes from observations and interview transcripts were analysed using a grounded theory approach.Results: Data were gathered from 60 hours of ward round observations, including 1024 individual patient discussions; 60 sociograms, interviews with healthcare professionals (60) and patients (7). The nature of discussions about AS and IPC on ward rounds vary across specialties and are affected by the content and structure of the clinical update provided, the consultant’s leadership and interaction style, and competing priorities at the bedside. Registrars act as gatekeepers, initiating antibiotic discussions; consultants are key decision-makers. Other team members have limited input in ward round conversations, despite having recognised roles in AS and IPC. Hierarchies in teams manifest themselves on ward rounds in where staff position themselves, influencing their contribution to care. Varied leadership styles affect ward-round dynamics, in particular, whether nurses and patients are actively engaged in key decisions on infection management and antibiotic therapy, and whether actions are assigned to i

  • 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
    Pallett SJC, Denny S, Patel A, Charani E, Mughal N, Stebbing J, Davies G, Moore Let al., 2021,

    Point-of-care SARS-CoV-2 serological assays for enhanced case finding in a UK inpatient population.

    , Scientific Reports, Vol: 11, Pages: 1-8, ISSN: 2045-2322

    Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Case identification is currently made by real-time polymerase chain reaction (PCR) during the acute phase and largely restricted to healthcare laboratories. Serological assays are emerging but independent validation is urgently required to assess their utility. We evaluated five different point-of-care (POC) SARS-CoV-2 antibody test kits against PCR, finding concordance across the assays (n=15). We subsequently tested 200 patients using the OrientGene COVID-19 IgG/IgM Rapid Test Cassette and find a sensitivity of 74% in the early infection period (day 5-9 post symptom onset), with 100% sensitivity not seen until day 13, demonstrating inferiority to PCR testing in the infectious period. Negative rate was 96%, but in validating the serological tests uncovered potential false-negatives from PCR testing late-presenting cases. A positive predictive value (PPV) of 37% in the general population precludes any use for general screening. Where a case definition is applied however, the PPV is substantially improved (95·4%), supporting use of serology testing in carefully targeted, high-risk populations. Larger studies in specific patient cohorts, including those with mild infection are urgently required to inform on the applicability of POC serological assays to help control the spread of SARS-CoV-2 and improve case finding of patients that may experience late complications.

  • Journal article
    Rodriguez-Manzano J, Malpartida-Cardenas K, Moser N, Pennisi I, Cavuto M, Miglietta L, Moniri A, Penn R, Satta G, Randell P, Davies F, Bolt F, Barclay W, Holmes A, Georgiou Pet al., 2021,

    Handheld point-of-care system for rapid detection of SARS-CoV-2 extracted RNA in under 20 min

    , ACS Central Science, Vol: 7, Pages: 307-317, ISSN: 2374-7943

    The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (<20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against extracted RNA from 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 91% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 ± 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n = 52), showing average detection times of 12.68 ± 2.56 min for positive samples (n = 34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geolocalization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.

  • Journal article
    Singh S, Charani E, Devi S, Sharma A, Edathadathil F, Kumar A, Warrier A, Shareek PS, Jaykrishnan A, Ellangovan Ket al., 2021,

    A road-map for addressing antimicrobial resistance in low- and middle-income countries: lessons learnt from the public private participation and co-designed antimicrobial stewardship programme in the State of Kerala, India

    , Antimicrobial Resistance and Infection Control, Vol: 10, ISSN: 2047-2994

    BackgroundThe global concern over antimicrobial resistance (AMR) is gathering pace. Low- and middle-income countries (LMICs) are at the epicentre of this growing public health threat and governmental and healthcare organizations are at different stages of implementing action plans to tackle AMR. The South Indian state of Kerala was one of the first in India to implement strategies and prioritize activities to address this public health threat.StrategiesThrough a committed and collaborative effort from all healthcare related disciplines and its professional societies from both public and private sector, the Kerala Public Private Partnership (PPP) has been able to deliver a state-wide strategy to tackle AMR A multilevel strategic leadership model and a multilevel implementation approach that included developing state-wide antibiotic clinical guidelines, a revision of post-graduate and undergraduate medical curriculum, and a training program covering all general practitioners within the state the PPP proved to be a successful model for ensuring state-wide implementation of an AMR action plan. Collaborative work of multi-professional groups ensured co-design and development of disease based clinical treatment guidelines and state-wide infection prevention policy. Knowledge exchange though international and national platforms in the form of workshops for sharing of best practices is critical to success. Capacity building at both public and private institutions included addressing practical and local solutions to the barriers e.g. good antibiotic prescription practices from primary to tertiary care facility and infection prevention at all levels.ConclusionThrough 7 years of stakeholder engagement, lobbying with government, and driving change through co-development and implementation, the PPP successfully delivered an antimicrobial stewardship plan across the state. The roadmap for the implementation of the Kerala PPP strategic AMR plan can provide learning for other state

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