31 results found
Watson O, Alhaffar M, Mehchy Z, et 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.
Ragonnet-Cronin M, Boyd O, Geidelberg L, et 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.
Myall A, Peach RL, Wan Y, et 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>
Pi L, Expert P, Clarke JM, et 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>
Boonyasiri A, Jauneikaite E, Brinkac LM, et al., 2021, Genomic and clinical characterisation of multidrug-resistant carbapenemase-producing ST231 and ST16 Klebsiella pneumoniae isolates colonising patients at Siriraj hospital, Bangkok, Thailand from 2015 to 2017., BMC Infectious Diseases, Vol: 21, Pages: 1-11, ISSN: 1471-2334
BACKGROUND: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data. METHODS: The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were "colonised" or "infected" with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes. RESULTS: Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n = 18) and CPE-colonised patients who developed CPE infections during the study (n = 3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major
Aliabadi S, Anyanwu P, Beech E, et 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, 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
Knock E, Whittles L, Lees J, et al., 2020, Report 41: The 2020 SARS-CoV-2 epidemic in England: key epidemiological drivers and impact of interventions
England has been severely affected by COVID-19. We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional 2020 surveillance data. Only national lockdown brought the reproduction number below 1 consistently; introduced one week earlier in the first wave it could have reduced mortality by 23,300 deaths on average. The mean infection fatality ratio was initially ~1.3% across all regions except London and halved following clinical care improvements. The infection fatality ratio was two-fold lower throughout in London, even when adjusting for demographics. The infection fatality ratio in care homes was 2.5-times that in the elderly in the community. Population-level infection-induced immunity in England is still far from herd immunity, with regional mean cumulative attack rates ranging between 4.4% and 15.8%.
Boonyasiri A, Jauneikaite E, Brinkac LM, et al., 2020, Genomic epidemiology of carbapenemase-producing Enterobacteriaceae in hospitalised patients in Bangkok, Thailand from 2015 to 2017, Publisher: ELSEVIER SCI LTD, Pages: 28-29, ISSN: 1201-9712
Gaythorpe K, Bhatia S, Mangal T, et al., 2020, Report 37: Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility
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. A systematic literature review was conducted in PubMed. Reviewers extracted data from relevant, peer-reviewed studies published 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.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 experience clinically mild disease or remain asymptomatically infected. More comprehensive contact-tracing studie
Ellington MJ, Davies F, Jauneikaite E, et al., 2020, A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid, Clinical Infectious Diseases, Vol: 71, Pages: 2553-2560, ISSN: 1058-4838
BACKGROUND: Early and accurate treatment of infections due to carbapenem-resistant organisms is facilitated by rapid diagnostics but rare resistance mechanisms can compromise detection. One year after a GES-5 carbapenemase-positive Klebsiella oxytoca infection was identified by whole genome sequencing (WGS) (later found to be part of a cluster of three cases), a cluster of 11 patients with GES-5-positive K. oxytoca was identified over 18 weeks in the same hospital.METHODS: Bacteria were identified by MALDI-TOF, antimicrobial susceptibility testing followed EUCAST guidelines. Ertapenem-resistant isolates were referred to Public Health England for characterization using PCR detection of GES, pulse-field gel electrophoresis (PFGE) and WGS for the second cluster.RESULTS: The identification of the first GES-5 K. oxytoca isolate was delayed, being identified on WGS. A GES-gene PCR informed the occurrence of the second cluster in real-time. In contrast to PFGE, WGS phylogenetic analysis refuted an epidemiological link between the two clusters; it also suggested a cascade of patient-to-patient transmission in the later cluster. A novel GES-5-encoding plasmid was present in K. oxytoca,E. coli and E. cloacae isolates from unlinked patients within the same hospital group and in human and wastewater isolates from three hospitals elsewhere in the UK.CONCLUSIONS: Genomic sequencing revolutionized the epidemiological understanding of the clusters, it also underlined the risk of covert plasmid propagation in healthcare settings and revealed the national distribution of the resistance-encoding plasmid. Sequencing results also informed and led to the ongoing use of enhanced diagnostic tests for detecting carbapenemases locally and nationally.
Bianchi-Jassir F, Paul P, To K-N, et al., 2020, Systematic review of Group B Streptococcal capsular types, sequence types and surface proteins as potential vaccine candidates., Vaccine, Vol: 38, Pages: 6682-6694, ISSN: 0264-410X
BACKGROUND: 21 million pregnant women worldwide (18%) are estimated to carry Group B Streptococcus (GBS), which is a risk for invasive disease in newborns, pregnant women, and stillbirths. Adults ≥ 60 years or with underlying health conditions are also vulnerable to invasive GBS disease. We undertook systematic reviews on GBS organism characteristics including: capsular polysaccharide (serotype), sequence type (multi-locus sequence types (MLST)), and virulence proteins. We synthesised data by at-risk populations, to inform vaccine development. METHODS: We conducted systematic reviews and meta-analyses to estimate proportions of GBS serotypes for at risk populations: maternal colonisation, invasive disease in pregnant women, stillbirths, infants 0-90 days age, and older adults (≥60 years). We considered regional variation and time trends (2001-2018). For these at-risk population groups, we summarised reported MLST and surface proteins. RESULTS: Based on 198 studies (29247isolates), 93-99% of GBS isolates were serotypes Ia, Ib, II, III, IV and V. Regional variation is likely, but data gaps are apparent, even for maternal colonisation which has most data. Serotype III dominates for infant invasive disease (60%) and GBS-associated stillbirths (41%). ST17 accounted for a high proportion of infant invasive disease (41%; 95%CI: 35-47) and was found almost exclusively in serotype III strains, less present in maternal colonisation (9%; 95%CI:6-13),(4%; 95%CI:0-11) infant colonisation, and adult invasive disease (4%, 95%CI:2-6). Percentages of strains with at least one of alp 1, alp2/3, alpha C or Rib surface protein targets were 87% of maternal colonisation, 97% infant colonisation, 93% infant disease and 99% adult invasive disease. At least one of three pilus islands proteins were reported in all strains. DISCUSSION: A hexavalent vaccine (serotypes Ia, Ib, II, III, IV and V) might provide comprehensive cover for all at-risk populations. Survei
Hogan A, Winskill P, Watson O, et al., 2020, Report 33: Modelling the allocation and impact of a COVID-19 vaccine
Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups. We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 and the level of healthcare available to effectively treat those with disease. Within a country, we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly and other high-risk groups. However, if a larger supply is available, the optimal strategy switches to targeting key transmitters (i.e. the working age population and potentially children) to indirectly protect the elderly and vulnerable. Given the likely global dose supply in 2021 (2 billion doses with a two-dose vaccine), we find that a strategy in which doses are allocated to countries in proportion to their population size is close to optimal in averting deaths. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning.
Monod M, Blenkinsop A, Xi X, et al., 2020, Report 32: Targeting interventions to age groups that sustain COVID-19 transmission in the United States
Following inial declines, in mid 2020, a resurgence in transmission of novel coronavirus disease (COVID-19) has occurred in the United States and parts of Europe. Despite the wide implementaon of non-pharmaceucal inter-venons, it is sll not known how they are impacted by changing contact paerns, age and other demographics. As COVID-19 disease control becomes more localised, understanding the age demographics driving transmission and how these impact the loosening of intervenons such as school reopening is crucial. Considering dynamics for the United States, we analyse aggregated, age-speciﬁc mobility trends from more than 10 million individuals and link these mechaniscally to age-speciﬁc COVID-19 mortality data. In contrast to previous approaches, we link mobility to mortality via age speciﬁc contact paerns and use this rich relaonship to reconstruct accurate trans-mission dynamics. Contrary to anecdotal evidence, we ﬁnd lile support for age-shis in contact and transmission dynamics over me. We esmate that, unl August, 63.4% [60.9%-65.5%] of SARS-CoV-2 infecons in the United States originated from adults aged 20-49, while 1.2% [0.8%-1.8%] originated from children aged 0-9. In areas with connued, community-wide transmission, our transmission model predicts that re-opening kindergartens and el-ementary schools could facilitate spread and lead to considerable excess COVID-19 aributable deaths over a 90-day period. These ﬁndings indicate that targeng intervenons to adults aged 20-49 are an important con-sideraon in halng resurgent epidemics, and prevenng COVID-19-aributable deaths when kindergartens and elementary schools reopen.
Collin SM, Groves N, O' Sullivan C, et al., 2020, Uncovering infant group B streptococcal (GBS) disease clusters in the UK and Ireland through genomic analysis: a population-based epidemiological study, Clinical Infectious Diseases, ISSN: 1058-4838
Ledda A, Cummins M, Shaw LP, et al., 2020, Hospital outbreak of carbapenem-resistant Enterobacteriales associated with an OXA-48 plasmid carried mostly byEscherichia coliST399
<jats:title>Abstract</jats:title><jats:p>A hospital outbreak of carbapenem-resistant Enterobacteriales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacteriales were involved in the outbreak.<jats:italic>Escherichia coli</jats:italic>ST399 accounted for 20/55 of all the isolates. Comparative genomics with publicly available<jats:italic>E. coli</jats:italic>ST399 sequence data showed that the outbreak isolates formed a unique clade. The OXA-48 plasmid identified in the outbreak differed from other known plasmids by an estimated five homologous recombination events. We estimated a lower bound to the plasmid conjugation rate to be 0.23 conjugation events per lineage per year. Our analysis suggests co-evolution between the plasmid and its main bacterial host to be a key driver of the outbreak. This is the first study to report carbapenem-resistant<jats:italic>E. coli</jats:italic>ST399 carrying OXA48 as the main cause of a plasmid-borne outbreak within a hospital setting. This study supports complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.</jats:p>
Rodriguez Manzano J, Moser N, Malpartida Cardenas K, et al., 2020, Rapid detection of mobilized colistin resistance using a nucleic acid based lab-on-a-chip diagnostic system, Scientific Reports, Vol: 10, ISSN: 2045-2322
The increasing prevalence of antimicrobial resistance is a serious threat to global public health. One of the most concerning trends is the rapid spread of Carbapenemase-Producing Organisms (CPO), where colistin has become the last-resort antibiotic treatment. The emergence of colistin resistance, including the spread of mobilized colistin resistance (mcr) genes, raises the possibility of untreatable bacterial infections and motivates the development of improved diagnostics for the detection of colistin-resistant organisms. This work demonstrates a rapid response for detecting the most recently reported mcr gene, mcr−9, using a portable and affordable lab-on-a-chip (LoC) platform, offering a promising alternative to conventional laboratory-based instruments such as real-time PCR (qPCR). The platform combines semiconductor technology, for non-optical real-time DNA sensing, with a smartphone application for data acquisition, visualization and cloud connectivity. This technology is enabled by using loop-mediated isothermal amplification (LAMP) as the chemistry for targeted DNA detection, by virtue of its high sensitivity, specificity, yield, and manageable temperature requirements. Here, we have developed the first LAMP assay for mcr−9 - showing high sensitivity (down to 100 genomic copies/reaction) and high specificity (no cross-reactivity with other mcr variants). This assay is demonstrated through supporting a hospital investigation where we analyzed nucleic acids extracted from 128 carbapenemase-producing bacteria isolated from clinical and screening samples and found that 41 carried mcr−9 (validated using whole genome sequencing). Average positive detection times were 6.58 ± 0.42 min when performing the experiments on a conventional qPCR instrument (n = 41). For validating the translation of the LAMP assay onto a LoC platform, a subset of the samples were tested (n = 20), showing average detection times o
Jauneikaite E, Ferguson T, Mosavie M, et al., 2020, Staphylococcus aureus colonisation and acquisition of skin and soft tissue infection amongst Royal Marines recruits: A prospective cohort study, Clinical Microbiology and Infection, Vol: 26, Pages: 381.e1-381.e6, ISSN: 1198-743X
Objectives: Skin and soft tissue infections (SSTIs) are a serious health issue for military personnel. Of particular importance are those caused by MRSA and PVL-positive S. aureus (PVL-SA), as they have been associated with outbreaks of SSTIs. A prospective observational study was conducted in Royal Marines recruits to investigate the prevalence of PVL-SA carriage and any association with SSTIs.Methods: 1,012 RM recruits were followed through a 32-week training programme, with nose and throat swabs obtained at weeks 1, 6, 15 and 32. S. aureus isolates were characterised by antibiotic susceptibility testing, spa typing, presence of mecA/C and PVL genes. Retrospective review of the clinical notes for SSTI acquisition was conducted.Results: S. aureus colonisation decreased from week-1 to week-32 (41% to 26%, p<0.0001). Of 1,168 S. aureus isolates, 3/1168 (0.3%) were MRSA and 10/1168 (0.9%) PVL-positive (all MSSA) and 169/1168 (14.5%) were resistant to clindamycin. Isolates showed genetic diversity with 238 different spa types associated with 25 MLST clonal complexes. SSTIs were seen in 35% (351/989) of recruits with 3 training days lost per recruit. SSTI acquisition rate was reduced amongst persistent carriers (p<0.0283). Conclusions: Nose and throat carriage of MRSA and PVL-SA was low amongst recruits, despite a high incidence of SSTIs being reported particularly cellulitis. Carriage strains were predominantly MSSA with a marked diversity of genotypes. Persistent nose and/or throat carriage was not associated with SSTI acquisition. Putative person-to-person transmission within troops was identified based on spa typing requiring further research to confirm and explore potential transmission routes.
Collin SM, Lamb P, Jauneikaite E, et al., 2019, Hospital clusters of invasive Group B Streptococcal disease: a systematic review, Journal of Infection, Vol: 79, Pages: 521-527, ISSN: 0163-4453
Objectives: To characterize outbreaks of invasive Group B Streptococcal (iGBS) disease in hospitals.Methods: Systematic review using electronic databases to identify studies describing iGBS outbreaks/clusters or cross-infection/acquisition in healthcare settings where ‘cluster’ was defined as ≥2 linked cases. PROSPERO CRD42018096297.Results: Twenty-five references were included describing 30 hospital clusters (26 neonatal, 4 adult) in 11 countries from 1966 to 2019. Cross-infection between unrelated neonates was reported in 19 clusters involving an early-onset (<7 days of life; n = 3), late-onset (7–90 days; n = 13) index case or colonized infant (n = 3) followed by one or more late-onset cases (median serial interval 9 days (IQR 3–17, range 0–50 days, n = 45)); linkage was determined by phage typing in 3 clusters, PFGE/MLST/PCR in 8, WGS in 4, non-molecular methods in 4. Postulated routes of transmission in neonatal clusters were via clinical personnel and equipment, particularly during periods of crowding and high patient-to-nurse ratio. Of 4 adult clusters, one was attributed to droplet spread between respiratory cases, one to handling of haemodialysis catheters and two unspecified.Conclusions: Long intervals between cases were identified in most of the clusters, a characteristic which potentially hinders detection of GBS hospital outbreaks without enhanced surveillance supported by genomics.
Herbert R, Hatcher J, Jauneikaite E, et al., 2019, Two-year analysis of Clostridium difficile ribotypes associated with increased severity, Journal of Hospital Infection, Vol: 103, Pages: 388-394, ISSN: 0195-6701
BackgroundCertain Clostridium difficile ribotypes have been associated with complex disease phenotypes including recurrence and increased severity, especially the well-described hypervirulent ribotype RT027. In this study we set out to determine the pattern of ribotypes causing infection and association if any with severity.MethodsAll faecal samples submitted to a large diagnostic laboratory for C. difficile testing between 2011 and 2013 were subject to routine testing and cultured. All C. difficile isolates were ribotyped and associated clinical and demographic patient data were retrieved then linked to ribotyping data.ResultsA total of 86 distinct ribotypes were identified from 705 isolates of C. difficile. Ribotypes RT002 and RT015 were the most prevalent (22.5%, n=159). Only five isolates (0.7%) were the hypervirulent RT027. Ninety of 450 (20%) patients with clinical information available died within 30-days of C. difficile isolation. Ribotype RT220, one of the ten commonest ribotypes, was associated with elevated median C-reactive protein and significantly increased 30-day all-cause mortality when compared with ribotypes RT002 and RT015, and with all other ribotypes found in the study.ConclusionsA wide range of C. difficile ribotypes were responsible for C. difficile infection presentations. Although C. difficile-associated mortality has reduced in recent years, expansion of lineages associated with increased severity could herald increases in future mortality. Enhanced surveillance for emerging lineages such as RT220 that are associated with more severe disease is required, with genomic approaches to dissect pathogenicity.
Lynskey NN, Jauneikaite E, Li H-K, et al., 2019, Emergence of dominant toxigenic M1T1 Streptococcus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study, Lancet Infectious Diseases, Vol: 19, Pages: 1209-1218, ISSN: 1473-3099
BackgroundEngland is experiencing scarlet fever activity unprecedented in modern times. In 2016, England’s scarlet fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular-epidemiological investigation of these events and emergence of a new emm1 lineage.Methods We analysed changes in S. pyogenes emm-genotypes, and notifications of scarlet fever and invasive disease 2014-2016 using regional (North-West London) and national (England and Wales) data. We analysed genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009-2016, and compared 2800 global emm1 sequences. Expression of Streptococcal pyrogenic exotoxin (Spe)A by sequenced non-invasive emm1 isolates was quantified.FindingsCoincident with national increases in scarlet fever and invasive disease notifications, emm1 S. pyogenes increased significantly, from 19% (28/147) of upper respiratory tract isolates in MarchMay 2015, to 32·6% (47/144) in the same period 2016 in North-West London (χ2 (1df)=7·024, p=0·008), and from 31% (183/587) of invasive isolates in March-May 2015, to 41·9% (267/637)in the same period 2016 nationally (χ2 (1df)=15·16, p=0·0001). Sequences of emm1 isolates from 2009-2016 demonstrated emergence of a new emm1 lineage (M1UK), with overlap of pharyngitis, scarlet fever, and invasive M1UK strains, that could be genotypically distinguished from pandemic emm1 isolates (M1global). Compared with M1global, median expression of SpeA increased 9-fold in M1UK isolates (M1global, median=20·9 ng/ml, IQ range=21.3; (M1UK, median=190·2 ng/ml, IQ3 range 31.5; Mann-Whitney p<0·001). M1UK expanded nationally to represent 84% (252/299) of all emm1 genomes in 2016; phylogenetic analysis of published datasets identified single M1UK isolates in Denmark and USA.
Aliabadi S, Honeyford K, Jauneikaite E, et al., 2019, Risk factors for E. coli Susceptibility in Bloods Stream Infections in England Between 2013-2017, Publisher: OXFORD UNIV PRESS, Pages: 111-111, ISSN: 1101-1262
Martinez-Vega R, Jauneikaite E, Thoon KC, et al., 2019, Risk factor profiles and clinical outcomes for children and adults with pneumococcal infections in Singapore: a need to expand vaccination policy?, PLoS ONE, Vol: 14, ISSN: 1932-6203
Invasive pneumococcal infection is a major cause of morbidity and mortality worldwide despite the availability of pneumococcal vaccines. The aim of this study was to re-evaluate the clinical syndromes, prognostic factors and outcomes for pneumococcal disease in adults and children in Singapore during the period before and after the introduction of the pneumococcal vaccine. We retrospectively analyzed a large cohort of patients admitted to the four main public hospitals in Singapore with S. pneumoniae infection between 1997 and 2013. A total of 889 (64% of all isolates identified in the clinical laboratories) cases were included in the analysis; 561 (63.1%) were adult (≥16 years) cases with a median age of 62 years and 328 (36.9%) were paediatric cases with a median age of 3 years. Bacteraemic pneumonia was the most common syndrome in both groups (69.3% vs. 44.2%), followed by primary bacteraemia without pneumonia (14.3% vs. 13.4%), meningitis (6.4% vs. 7.6%) and non-bacteraemic pneumonia (5.2% vs. 21%). The major serotypes in adults were 3, 4, 6B, 14, 19F and 23F whereas in children they were 14, 6B and 19F, accounting both for nearly half of pneumococcal disease cases. No particular serotype was associated with mortality or severity of the pneumococcal disease. Overall mortality rate was 18.5% in adults and 3% in children. Risk factors for mortality included acute cardiac events in adults, meningitis in children and critical illness and bilateral pulmonary infiltrates in both adults and children. Penicillin resistance was not associated with increased mortality. Our results agree with global reports that the course of pneumococcal disease and its clinical outcome were more severe in adults than in children. The main serotypes causing invasive disease were all covered by the vaccines in use. The high mortality rates reflect an urgent need to increase vaccination coverage in both adults and children to tackle this vaccine-preventable infection.
Mosavie M, Blandy O, Jauneikaite E, et al., 2019, Sampling and diversity of Escherichia coli from the enteric microbiota in patients with Escherichia coli bacteraemia, BMC Research Notes, Vol: 12, ISSN: 1756-0500
ObjectiveThe increase in Escherichia coli bloodstream infections mandates better characterisation of the relationship between commensal and invasive isolates. This study adopted a simple approach to characterize E. coli in the gut reservoir from patients with either E. coli or other Gram-negative bacteraemia, or those without bacteraemia, establishing strain collections suitable for genomic investigation. Enteric samples from patients in the three groups were cultured on selective chromogenic agar. Genetic diversity of prevailing E. coli strains in gut microbiota was estimated by RAPD-PCR.ResultsEnteric samples from E. coli bacteraemia patients yielded a median of one E. coli RAPD pattern (range 1–4) compared with two (range 1–5) from groups without E. coli bacteraemia. Of relevance to large-scale clinical studies, observed diversity of E. coli among hospitalised patients was not altered by sample type (rectal swab or stool), nor by increasing the colonies tested from 10 to 20. Hospitalised patients demonstrated an apparently limited diversity of E. coli in the enteric microbiota and this was further reduced in those with E. coli bacteraemia. The reduced diversity of E. coli within the gut during E. coli bacteraemia raises the possibility that dominant strains may outcompete other lineages in patients with bloodstream infection.
To K, Cornwell E, Daniel R, et al., 2019, Evaluation of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of group B streptococcus, BMC Research Notes, Vol: 12, ISSN: 1756-0500
ObjectiveGroup B Streptococcus (GBS) is a leading cause of neonatal meningitis and sepsis worldwide. Intrapartum antibiotics given to women carrying GBS are an effective means of reducing disease in the first week of life. Rapid and reliable tests are needed to accurately identify GBS from these women for timely intrapartum antibiotic administration to prevent neonatal disease. Many laboratories now use matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) by direct plating or cell lysis for the identification of GBS isolates. The cell lysis step increases time to results for clinical samples and is more complex to perform. Therefore, we seek to evaluate the sensitivity and specificity of the quicker and more rapid direct plating method in identifying GBS.ResultsWe directly compared swab isolates analysed by both direct plating and cell lysis method and demonstrated that direct plating has a sensitivity and specificity of 0.97 and 1, respectively, compared to an additional cell lysis step. We demonstrated that MALDI-TOF MS can be successfully used for batch processing by the direct plating method which saves time. These results are reassuring for laboratories worldwide who seek to identify GBS from swabs samples as quickly as possible.
Jauneikaite E, Jefferies JMC, Churton NWV, et al., 2019, Genetic diversity of Streptococcus pneumoniae causing meningitis and sepsis in Singapore during the first year of PCV7 implementation, Emerging Microbes and Infections, Vol: 3, Pages: 1-7, ISSN: 2222-1751
Streptococcus pneumoniae is a major cause of sepsis, meningitis and respiratory disease worldwide. Pneumococcal conjugate vaccines (PCVs) have now been implemented in many countries worldwide, including Singapore. To evaluate the effectiveness of these vaccines, pneumococcal surveillance studies are required. Detailed and unified pneumococcal epidemiology data are currently scarce in South East Asia. Thus, we present data on invasive pneumococcal (IPD) isolates from Singapore that could assist in evaluating the effectiveness of pneumococcal vaccine in Singapore. One hundred and fifty-nine invasive pneumococcal disease isolates were received by the National Public Health Laboratory in Singapore between June 2009 and August 2010. Isolates were characterized using serotyping and multilocus sequence typing. Twenty-four different serotypes were found, the most common of which were 19A, 3, 7F, 23F, 6B, 14, 8 and 19F (in rank order). One hundred and two sequence types were observed, of which 38 were novel due to new alleles or new combinations of already existing alleles. Based on the Simpson’s Index of Diversity, serotypes 3, 6B and 19A were the most genetically diverse. Novel sequence types were more prevalent among conjugate vaccine serotypes 3, 19F and 23F and non-conjugate vaccine serotype 8, serogroup 15 and in non-typable isolates. We have demonstrated considerable genetic diversity among invasive pneumococci before and during the widespread use of conjugate vaccines in Singapore. Approximately half of all novel IPD clones identified in this study were non-conjugate vaccine serotypes. Although PCVs would target the most common serotypes, the high genetic diversity in non-vaccine serotypes would require further surveillance studies.
Jauneikaite E, Kapatai G, Davies F, et al., 2018, Serial clustering of late onset group B streptococcal infections in the neonatal unit - a genomic re-evaluation of causality, Clinical Infectious Diseases, Vol: 67, Pages: 854-860, ISSN: 1058-4838
Background. Invasive Group B streptococcus (GBS) is a major cause of serious neonatal infection. Current strategies to reduce early onset GBS disease have no impact on late onset disease (LOD). Although GBS is a normal part of the enteric microbiota in healthy term infants, LOD cases arising in the neonatal intensive care unit setting raise questions about mode of acquisition.Methods. Enhanced surveillance for any case of late onset GBS sepsis admitted to a level 3, 24-bed neonatal intensive care unit over a 2 year period was instituted following a cluster of four cases. All late onset GBS isolates were serotyped and genomes sequenced. Rectal screening of neonates for GBS was undertaken weekly. Healthcare workers and parents were not screened.Results. Over 24 months, a total of 12 late onset invasive GBS episodes were identified (incidence 0.6/1000 live births). Genomic analysis revealed that 11/12 GBS isolates (92%) were linked to at least one other LOD isolate. Four isolates from the first cluster were serotype V, resistant to macrolides and lincosamides, providing early evidence of a common source. Sequencing confirmed isolates were indistinguishable, or distinguishable by 1 SNP, from each other, and distinct from contemporary serotype V GBS. Although a common environmental source was not identified, prompt infection prevention interventions were instituted and no further serotype V GBS infections arose. Prospective surveillance identified three further clusters of LOD due to serotypes Ia, Ib, and III, leading to re-evaluation of interventions required for preventing GBS LOD. Conclusion. Acquisition routes for LOD GBS in the neonatal unit are poorly understood; such cases may not necessarily be sporadic. Within this neonatal unit, our data suggest that a single case of LOD GBS sepsis should be considered a potential nosocomial transmission event warranting prompt investigation, heightened infection prevention vigilance and action where required.
Jauneikaite E, Khan-Orakzai Z, Kapatai G, et al., 2016, Nosocomial outbreak of drug resistant Streptococcus pneumoniae serotype 9V in an adult respiratory medicine ward, Journal of Clinical Microbiology, Vol: 55, Pages: 776-782, ISSN: 1098-660X
Streptococcus pneumoniae infections arising in hospitalized patients are often assumed to be sporadic, and linked to community carriage. Here, whole genome sequencing was used to demonstrate nosocomial acquisition of antimicrobially-resistant ST156-9V S. pneumoniae in 3 respiratory patients resulting in two bacteremias and one lower respiratory tract infection. Two of the cases arose in patients who had recently been discharged from hospital and were re-admitted from the community. Nosocomial spread was suspected solely because of a highly unusual resistance pattern and case presentations within 24h of one another. The outbreak highlights a potential for rapid transmission and short incubation period in the respiratory ward setting.
Jauneikaite E, Tocheva AS, Jefferies JMC, et al., 2015, Current methods for capsular typing of Streptococcus pneumoniae, JOURNAL OF MICROBIOLOGICAL METHODS, Vol: 113, Pages: 41-49, ISSN: 0167-7012
Litt DJ, Jauneikaite E, Tchipeva D, et al., 2012, Direct molecular typing of Bordetella pertussis from clinical specimens submitted for diagnostic quantitative (real-time) PCR, JOURNAL OF MEDICAL MICROBIOLOGY, Vol: 61, Pages: 1662-1668, ISSN: 0022-2615
Jauneikaite E, Churton N, Lin R, et al., 2012, Prevalence of serotypes and molecular types among Streptococcus pneumoniae isolates causing invasive disease in Singapore between June 2009 and August 2010, Publisher: ELSEVIER SCI LTD, Pages: E223-E223, ISSN: 1201-9712
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