SynopsisBackgroundAntimicrobial resistance (AMR) surveillance of bloodstream infections is challe... more SynopsisBackgroundAntimicrobial resistance (AMR) surveillance of bloodstream infections is challenging in low- and middle-income countries (LMICs), limited laboratory capacity preventing routine patient-level susceptibility testing. Other specimen types could provide an effective approach to surveillance.ObjectivesOur study aims to systematically evaluate the relationship between resistance prevalence in non-sterile sites and bloodstream infections.MethodsAssociations between resistance rates in Escherichia coli and Staphylococcus aureus isolates from blood and other specimens were estimated in Oxfordshire, UK, 1998-2018, comparing proportions resistant in each calendar year using time series cross-correlations and across drug-years. We repeated analysis across publicly-available data from four high-income and 12 middle-income countries, and in three hospitals/programmes in LMICs.Results8102 E. coli bloodstream infections, 322087 E. coli urinary tract infections, 6952 S. aureus bloo...
Objectives: Gram-negative organisms are common causes of bloodstream infection (BSI) during the n... more Objectives: Gram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population. Methods: We performed an epidemiological and sequencing based analysis of Gram-negative bloodstream infections in children <18 years old between 2008 and 2018 in Oxfordshire, UK. Results: 327 isolates (296 successfully sequenced) from 287 patients were included. The burden of infection was predominantly in neonates (124/327[38%]). Most infections were caused by Escherichia coli (149/327[46%])/Klebsiella spp. (69/327[21%]) and Enterobacter hormaechei (34/327[10%]). There was no evidence of an increasing incidence of E. coli BSIs (IRRy 0.96, 95%CI 0.90-1.30, p=0.30) and for Klebsiella spp. there was some evidence that the incidence decreased slightly (IRRy 0.91, 95%CI 0....
ABSTRACTIn a nationally representative UK community study, SARS-CoV-2 Omicron infections were ass... more ABSTRACTIn a nationally representative UK community study, SARS-CoV-2 Omicron infections were associated with fewer lower, and more upper, respiratory tract symptoms. Increases in sore throat (also common in PCR-negative participants), and a marked reduction in loss of taste/smell (previously highly specific), make Omicron harder to detect with symptom-based testing algorithms.
Additional file 1: Fig S1. Gene presence/absence heatmap showing AMR gene presence/absence agains... more Additional file 1: Fig S1. Gene presence/absence heatmap showing AMR gene presence/absence against the core genome phylogeny for E. coli. Fig S2: Time-scaled phylogenies for ST131, ST95, ST73 and ST69. Fig S3: Possible transmission within nursing homes. Fig S4: Gene presence/absence heatmap showing AMR gene presence/absence against the core genome phylogeny for Klebsiella spp. Fig S5: Manhattan plots of a pangenome wide association study of the association of genes with community/healthcare associated onset. Fig S6: Proportions of presumed infectious foci for CA and HA BSI. Fig S7: Timescaled phylogeny of Klebsiella pneumoniae ST490 with a heatmap of AMR genes. Fig S8: Phylogenetic tree of Klebsiella spp annotated with species and virulence score. Fig S9: top panel - plasmid types in the PlasmidFinder database identified in the major/other E. coli/Klebsiella spp., bottom left - plot showing kmer based plasmidome similarity (y-axis) against chromosome similarity (x-axis) for isolates...
Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) va... more Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with b...
The aim of this thesis is to use linked electronic health records of hospital admissions, and mic... more The aim of this thesis is to use linked electronic health records of hospital admissions, and microbiology and haematology results in order to inform management of infections in Oxfordshire, and more generally worldwide. Escherichia coli is one of the leading bacterial pathogens causing bloodstream infections; not only is overall incidence rising, but rising resistance to commonly used empiric antibiotics is also a major concern. Despite playing such a significant role in the burden of infections, the epidemiology of E. coli bloodstream infections is still unclear, particularly when considering unselected populations. I showed that the rise in E. coli bloodstream infections in Oxfordshire is driven by truly community-associated cases, that is, cases identified in the first 48 hours of a hospital admission, or outside of a hospital admission, who had not been admitted to the hospital in the past year. Interestingly, the rate of increase in incidence was faster the further away the pr...
Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in lo... more Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in low/middle-income countries (LMICs) given limited laboratory capacity. Other specimens are easier to collect and process and are more likely to be culture-positive. In 8102 E. coli BSIs, 322,087 E. coli urinary tract infections, 6952 S. aureus BSIs and 112,074 S. aureus non-sterile site cultures from Oxfordshire (1998–2018), and other (55,296 isolates) rarer commensal opportunistic pathogens, antibiotic resistance trends over time in blood were strongly associated with those in other specimens (maximum cross-correlation per drug 0.51–0.99). Resistance prevalence was congruent across drug-years for each species (276/312 (88%) species-drug-years with prevalence within ± 10% between blood/other isolates). Results were similar across multiple countries in high/middle/low income-settings in the independent ATLAS dataset (103,559 isolates, 2004–2017) and three further LMIC hospitals/programmes (...
Background: Information on COVID-19 in representative community surveillance is limited, particul... more Background: Information on COVID-19 in representative community surveillance is limited, particularly regarding cycle threshold (Ct) values (a proxy for SARS-CoV-2 viral load) and symptoms. Methods: We included all positive nose and throat swabs between 26 April-11 October 2020 from the UK national COVID-19 Infection Survey, tested by RT-PCR for the N, S and ORF1ab genes. We investigated predictors of median Ct value using quantile regression. Results: 1892(0.22%) of 843,851 results were positive, 1362(72%), 185(10%) and 345(18%) for 3, 2 or 1 genes respectively. Ct for different genes were strongly correlated (rho=0.99) with overall median Ct 26.2 (IQR 19.7-31.1; range 10.3-37.6), corresponding to ~2,500 dC/ml (IQR 80-240,000). Ct values were independently lower in those reporting symptoms, with more genes detected, and in first (vs. subsequent) positives per-participant, with no evidence of independent effects of sex, ethnicity, age, deprivation or other test characteristics (p>...
We estimated the duration and determinants of antibody response after SARS-CoV-2 infection in the... more We estimated the duration and determinants of antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as ‘non-responders’ not developing anti-spike antibodies. These seronegative non-responders were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels a...
The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia... more The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; however the causes of this are unclear and effective interventions are therefore hard to design. In this study we sequenced 3468 sequential, unselected isolates over a decade in Oxfordshire, UK. We demonstrate that the observed increases in E. coli incidence were not driven by clonal expansion; instead, four major sequence types (STs) continue to dominate a stable population structure, with no evidence of adaptation to hospital/community settings. Conversely in Klebsiella spp. most infections are caused by sporadic STs with the exception of a local drug-resistant outbreak strain (ST490). Virulence elements are highly structured by ST in E. coli but not Klebsiella spp. where they occur in a diverse spectrum of STs and equally across healthcare and community settings. Most clinically hypervirulent (i.e. community-onset) Klebsiella BSIs h...
Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidenc... more Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidence base to guide interventions against this major public health concern is small. We aimed to investigate possible drivers of changes in the incidence of E coli bloodstream infection and antibiotic susceptibilities in Oxfordshire, UK, over the past two decades, while stratifying for time since hospital exposure. In this observational study, we used all available data on E coli bloodstream infections and E coli urinary tract infections (UTIs) from one UK region (Oxfordshire) using anonymised linked microbiological data and hospital electronic health records from the Infections in Oxfordshire Research Database (IORD). We estimated the incidence of infections across a two decade period and the annual incidence rate ratio (aIRR) in 2016. We modelled the data using negative binomial regression on the basis of microbiological, clinical, and health-care-exposure risk factors. We investigated inf...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 10, 2017
mcr-1-mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in tr... more mcr-1-mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug-resistant Enterobacteriaceae infections. Rates of human mcr-1 gastrointestinal carriage have historically been low. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1-positive+third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in a subset of mcr-1-positive+3GC-R strains. Fecal samples were collected from in-patients and out-patients submitting specimens to three hospitals (2011-2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (whole genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 characterized. Of 8,022 fecal samples collected, 497 (6.2%) were mcr-1-positive, and 182 (2.3%) harbored mcr-1-positive+3GC-R Enterobacteriaceae. W...
Background: mcr-1-mediated transmissible colistin resistance in Enterobacteriaceae is concerning,... more Background: mcr-1-mediated transmissible colistin resistance in Enterobacteriaceae is concerning, given colistin is frequently used as a treatment of last resort in multidrug-resistant Enterobacteriaceae infections. Reported rates of human mcr-1 gastrointestinal carriage have historically been low. Objectives: To identify trends in human gastrointestinal carriage of mcr-1 positive and mcr-1-positive/cefotaxime-resistant Enterobacteriaceae in Guangzhou, China, 2011-2016, and investigate the genetic contexts of mcr-1 in a subset of mcr-1-positive/cefotaxime-resistant strains using whole genome sequencing (WGS). Methods: Of 8,022 faecal samples collected, 497 (6.2%) were mcr-1- positive, and 182 (2.3%) mcr-1-positive/cefotaxime-resistant. Trends in carriage were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (Illumina), and genetic contexts of mcr-1 were characterised. Results: We observed marked increases in mcr-1 (now ~30% prevalence...
Understanding variability in clinical symptoms of SARS-CoV-2 community infections is key in manag... more Understanding variability in clinical symptoms of SARS-CoV-2 community infections is key in management of the ongoing COVID-19 pandemic. Here we bring together four large and diverse datasets deriving from routine testing, a population-representative household survey and participatory mobile surveillance in the United Kingdom and use cutting-edge unsupervised classification techniques from statistics and machine learning to characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases. We explore commonalities across datasets and by age bands. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. This is expected to have implications for identification and management of community SARS-CoV-2 cases.
The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndr... more The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is reduced with the B.1.617.2 variant (absolute difference of 10–13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in pr...
ABSTRACTBackgroundSeveral community-based studies have assessed the ability of different symptoms... more ABSTRACTBackgroundSeveral community-based studies have assessed the ability of different symptoms to identify COVID-19 infections, but few have compared symptoms over time (reflecting SARS-CoV-2 variants) and by vaccination status.MethodsUsing data and samples collected by the COVID-19 Infection Survey at regular visits to representative households across the UK, we compared symptoms in new PCR-positives and comparator test-negative controls.ResultsFrom 26/4/2020-7/8/2021, 27,869 SARS-CoV-2 PCR-positive episodes occurred in 27,692 participants (median 42 years (IQR 22-58)); 13,427 (48%) self-reported symptoms (“symptomatic positive episodes”). The comparator group comprised 3,806,692 test-negative visits (457,215 participants); 130,612 (3%) self-reported symptoms (“symptomatic negative visit”). Reporting of any symptoms in positive episodes varied over calendar time, reflecting changes in prevalence of variants, incidental changes (e.g. seasonal pathogens, schools re-opening) and va...
SynopsisBackgroundAntimicrobial resistance (AMR) surveillance of bloodstream infections is challe... more SynopsisBackgroundAntimicrobial resistance (AMR) surveillance of bloodstream infections is challenging in low- and middle-income countries (LMICs), limited laboratory capacity preventing routine patient-level susceptibility testing. Other specimen types could provide an effective approach to surveillance.ObjectivesOur study aims to systematically evaluate the relationship between resistance prevalence in non-sterile sites and bloodstream infections.MethodsAssociations between resistance rates in Escherichia coli and Staphylococcus aureus isolates from blood and other specimens were estimated in Oxfordshire, UK, 1998-2018, comparing proportions resistant in each calendar year using time series cross-correlations and across drug-years. We repeated analysis across publicly-available data from four high-income and 12 middle-income countries, and in three hospitals/programmes in LMICs.Results8102 E. coli bloodstream infections, 322087 E. coli urinary tract infections, 6952 S. aureus bloo...
Objectives: Gram-negative organisms are common causes of bloodstream infection (BSI) during the n... more Objectives: Gram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population. Methods: We performed an epidemiological and sequencing based analysis of Gram-negative bloodstream infections in children <18 years old between 2008 and 2018 in Oxfordshire, UK. Results: 327 isolates (296 successfully sequenced) from 287 patients were included. The burden of infection was predominantly in neonates (124/327[38%]). Most infections were caused by Escherichia coli (149/327[46%])/Klebsiella spp. (69/327[21%]) and Enterobacter hormaechei (34/327[10%]). There was no evidence of an increasing incidence of E. coli BSIs (IRRy 0.96, 95%CI 0.90-1.30, p=0.30) and for Klebsiella spp. there was some evidence that the incidence decreased slightly (IRRy 0.91, 95%CI 0....
ABSTRACTIn a nationally representative UK community study, SARS-CoV-2 Omicron infections were ass... more ABSTRACTIn a nationally representative UK community study, SARS-CoV-2 Omicron infections were associated with fewer lower, and more upper, respiratory tract symptoms. Increases in sore throat (also common in PCR-negative participants), and a marked reduction in loss of taste/smell (previously highly specific), make Omicron harder to detect with symptom-based testing algorithms.
Additional file 1: Fig S1. Gene presence/absence heatmap showing AMR gene presence/absence agains... more Additional file 1: Fig S1. Gene presence/absence heatmap showing AMR gene presence/absence against the core genome phylogeny for E. coli. Fig S2: Time-scaled phylogenies for ST131, ST95, ST73 and ST69. Fig S3: Possible transmission within nursing homes. Fig S4: Gene presence/absence heatmap showing AMR gene presence/absence against the core genome phylogeny for Klebsiella spp. Fig S5: Manhattan plots of a pangenome wide association study of the association of genes with community/healthcare associated onset. Fig S6: Proportions of presumed infectious foci for CA and HA BSI. Fig S7: Timescaled phylogeny of Klebsiella pneumoniae ST490 with a heatmap of AMR genes. Fig S8: Phylogenetic tree of Klebsiella spp annotated with species and virulence score. Fig S9: top panel - plasmid types in the PlasmidFinder database identified in the major/other E. coli/Klebsiella spp., bottom left - plot showing kmer based plasmidome similarity (y-axis) against chromosome similarity (x-axis) for isolates...
Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) va... more Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with b...
The aim of this thesis is to use linked electronic health records of hospital admissions, and mic... more The aim of this thesis is to use linked electronic health records of hospital admissions, and microbiology and haematology results in order to inform management of infections in Oxfordshire, and more generally worldwide. Escherichia coli is one of the leading bacterial pathogens causing bloodstream infections; not only is overall incidence rising, but rising resistance to commonly used empiric antibiotics is also a major concern. Despite playing such a significant role in the burden of infections, the epidemiology of E. coli bloodstream infections is still unclear, particularly when considering unselected populations. I showed that the rise in E. coli bloodstream infections in Oxfordshire is driven by truly community-associated cases, that is, cases identified in the first 48 hours of a hospital admission, or outside of a hospital admission, who had not been admitted to the hospital in the past year. Interestingly, the rate of increase in incidence was faster the further away the pr...
Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in lo... more Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in low/middle-income countries (LMICs) given limited laboratory capacity. Other specimens are easier to collect and process and are more likely to be culture-positive. In 8102 E. coli BSIs, 322,087 E. coli urinary tract infections, 6952 S. aureus BSIs and 112,074 S. aureus non-sterile site cultures from Oxfordshire (1998–2018), and other (55,296 isolates) rarer commensal opportunistic pathogens, antibiotic resistance trends over time in blood were strongly associated with those in other specimens (maximum cross-correlation per drug 0.51–0.99). Resistance prevalence was congruent across drug-years for each species (276/312 (88%) species-drug-years with prevalence within ± 10% between blood/other isolates). Results were similar across multiple countries in high/middle/low income-settings in the independent ATLAS dataset (103,559 isolates, 2004–2017) and three further LMIC hospitals/programmes (...
Background: Information on COVID-19 in representative community surveillance is limited, particul... more Background: Information on COVID-19 in representative community surveillance is limited, particularly regarding cycle threshold (Ct) values (a proxy for SARS-CoV-2 viral load) and symptoms. Methods: We included all positive nose and throat swabs between 26 April-11 October 2020 from the UK national COVID-19 Infection Survey, tested by RT-PCR for the N, S and ORF1ab genes. We investigated predictors of median Ct value using quantile regression. Results: 1892(0.22%) of 843,851 results were positive, 1362(72%), 185(10%) and 345(18%) for 3, 2 or 1 genes respectively. Ct for different genes were strongly correlated (rho=0.99) with overall median Ct 26.2 (IQR 19.7-31.1; range 10.3-37.6), corresponding to ~2,500 dC/ml (IQR 80-240,000). Ct values were independently lower in those reporting symptoms, with more genes detected, and in first (vs. subsequent) positives per-participant, with no evidence of independent effects of sex, ethnicity, age, deprivation or other test characteristics (p>...
We estimated the duration and determinants of antibody response after SARS-CoV-2 infection in the... more We estimated the duration and determinants of antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as ‘non-responders’ not developing anti-spike antibodies. These seronegative non-responders were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels a...
The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia... more The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; however the causes of this are unclear and effective interventions are therefore hard to design. In this study we sequenced 3468 sequential, unselected isolates over a decade in Oxfordshire, UK. We demonstrate that the observed increases in E. coli incidence were not driven by clonal expansion; instead, four major sequence types (STs) continue to dominate a stable population structure, with no evidence of adaptation to hospital/community settings. Conversely in Klebsiella spp. most infections are caused by sporadic STs with the exception of a local drug-resistant outbreak strain (ST490). Virulence elements are highly structured by ST in E. coli but not Klebsiella spp. where they occur in a diverse spectrum of STs and equally across healthcare and community settings. Most clinically hypervirulent (i.e. community-onset) Klebsiella BSIs h...
Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidenc... more Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidence base to guide interventions against this major public health concern is small. We aimed to investigate possible drivers of changes in the incidence of E coli bloodstream infection and antibiotic susceptibilities in Oxfordshire, UK, over the past two decades, while stratifying for time since hospital exposure. In this observational study, we used all available data on E coli bloodstream infections and E coli urinary tract infections (UTIs) from one UK region (Oxfordshire) using anonymised linked microbiological data and hospital electronic health records from the Infections in Oxfordshire Research Database (IORD). We estimated the incidence of infections across a two decade period and the annual incidence rate ratio (aIRR) in 2016. We modelled the data using negative binomial regression on the basis of microbiological, clinical, and health-care-exposure risk factors. We investigated inf...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 10, 2017
mcr-1-mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in tr... more mcr-1-mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug-resistant Enterobacteriaceae infections. Rates of human mcr-1 gastrointestinal carriage have historically been low. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1-positive+third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in a subset of mcr-1-positive+3GC-R strains. Fecal samples were collected from in-patients and out-patients submitting specimens to three hospitals (2011-2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (whole genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 characterized. Of 8,022 fecal samples collected, 497 (6.2%) were mcr-1-positive, and 182 (2.3%) harbored mcr-1-positive+3GC-R Enterobacteriaceae. W...
Background: mcr-1-mediated transmissible colistin resistance in Enterobacteriaceae is concerning,... more Background: mcr-1-mediated transmissible colistin resistance in Enterobacteriaceae is concerning, given colistin is frequently used as a treatment of last resort in multidrug-resistant Enterobacteriaceae infections. Reported rates of human mcr-1 gastrointestinal carriage have historically been low. Objectives: To identify trends in human gastrointestinal carriage of mcr-1 positive and mcr-1-positive/cefotaxime-resistant Enterobacteriaceae in Guangzhou, China, 2011-2016, and investigate the genetic contexts of mcr-1 in a subset of mcr-1-positive/cefotaxime-resistant strains using whole genome sequencing (WGS). Methods: Of 8,022 faecal samples collected, 497 (6.2%) were mcr-1- positive, and 182 (2.3%) mcr-1-positive/cefotaxime-resistant. Trends in carriage were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (Illumina), and genetic contexts of mcr-1 were characterised. Results: We observed marked increases in mcr-1 (now ~30% prevalence...
Understanding variability in clinical symptoms of SARS-CoV-2 community infections is key in manag... more Understanding variability in clinical symptoms of SARS-CoV-2 community infections is key in management of the ongoing COVID-19 pandemic. Here we bring together four large and diverse datasets deriving from routine testing, a population-representative household survey and participatory mobile surveillance in the United Kingdom and use cutting-edge unsupervised classification techniques from statistics and machine learning to characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases. We explore commonalities across datasets and by age bands. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. This is expected to have implications for identification and management of community SARS-CoV-2 cases.
The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndr... more The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is reduced with the B.1.617.2 variant (absolute difference of 10–13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in pr...
ABSTRACTBackgroundSeveral community-based studies have assessed the ability of different symptoms... more ABSTRACTBackgroundSeveral community-based studies have assessed the ability of different symptoms to identify COVID-19 infections, but few have compared symptoms over time (reflecting SARS-CoV-2 variants) and by vaccination status.MethodsUsing data and samples collected by the COVID-19 Infection Survey at regular visits to representative households across the UK, we compared symptoms in new PCR-positives and comparator test-negative controls.ResultsFrom 26/4/2020-7/8/2021, 27,869 SARS-CoV-2 PCR-positive episodes occurred in 27,692 participants (median 42 years (IQR 22-58)); 13,427 (48%) self-reported symptoms (“symptomatic positive episodes”). The comparator group comprised 3,806,692 test-negative visits (457,215 participants); 130,612 (3%) self-reported symptoms (“symptomatic negative visit”). Reporting of any symptoms in positive episodes varied over calendar time, reflecting changes in prevalence of variants, incidental changes (e.g. seasonal pathogens, schools re-opening) and va...
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Papers by Karina-Doris Vihta