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Paul Turner

Publications and source records attributed to Paul Turner.

3 recordsLinked to original sources

Prospective characterisation of drug-resistant bloodstream infections in Africa and Asia (ACORN2): a surveillance network assessment.

BACKGROUND: Antimicrobial resistance (AMR) is a major global health threat, but there is scarcity of laboratory surveillance data linked to clinical information to determine burden and inform interventions, especially from low-income and middle-income countries. The ACORN2 study sought to address this through prospective case-based surveillance in 19 hospitals across Africa and Asia to characterise drug-resistant infections by origin, clinical syndrome, patient age, outcome, and geographical location. METHODS: Patients were enrolled on selected wards and clinical data were collected daily for community-acquired infections (CAIs). Point prevalence surveys for hospital-acquired infections (HAIs) were conducted weekly. Mortality was assessed at discharge and after 28 days. Linked microbiology data were extracted from local laboratory databases. Primary descriptive analyses focused on WHO Global Antimicrobial Resistance and Use Surveillance System pathogen (target organism) bloodstream infections (BSIs). Comparisons were adjusted for clustering by site using random effects models. FINDINGS: Over 31 months, 41&#x2009;907 infections were characterised from 41&#x2009;032 admissions. Two-thirds were children (19&#x2009;351; 47&#xb7;2%) or neonates (6649; 16&#xb7;2%). There were marked differences in pathogen incidence and antibiotic resistance when clinical infections were stratified by patient age category and infection origin (CAI/HAI). The highest rates of target organism AMR BSI were third-generation cephalosporin-resistant (3GC-R) Escherichia coli (718&#xb7;56/100&#x2009;000 blood cultured infection episodes), meticillin-resistant Staphylococcus aureus (586&#xb7;89/100&#x2009;000 blood cultured infection episodes), and 3GC-R Klebsiella pneumoniae (364&#xb7;92/100&#x2009;000 blood cultured infection episodes). In-hospital mortality was 13&#xb7;1% (166/1265) in patients with target organism BSI versus 6&#xb7;2% (1357/21&#x2009;845) in those with negative blood cultures, p<0&#xb7;0001. INTERPRETATION: ACORN2 has shown practical implementation of collecting linked clinical-laboratory AMR data in low-income and middle-income countries and identified a significant burden of WHO GLASS BSI. Adoption of the ACORN2 approach at scale might enhance use of diagnostic microbiology and improve the volume of clinical data included in national and global AMR surveillance datasets. FUNDING: Wellcome.

Humans

Factors associated with positive blood cultures in children in nine African and Asian countries: the ACORN2 surveillance network.

BACKGROUND: Blood culture (BC) in children has relatively low diagnostic yield and high contamination rates, limiting cost-effectiveness. We aimed to determine readily available baseline characteristics to identify hospitalised children with a likelihood of higher diagnostic yield in low- and middle-income countries. METHODS: We used data from ACORN2, a prospective clinical surveillance network including 19 hospitals across Africa and Asia. We included participants <18 years, hospitalised for a suspected infection, prescribed parenteral antibiotics and with a BC sample. Sociodemographic and clinical data were recorded for each infection episode and linked to routine microbiology data. We described true pathogen (non-contaminant) BC positivity proportion and performed mixed-effects logistic regression, with study site and patient as the random effect, to identify factors associated with BC positivity. RESULTS: Of the 26 407 paediatric infection episodes, 17 815 (67%) had a BC sample and 15 384 were included in the analysis. BC results were: true pathogens in 689 (4.5%), contaminants in 1399 (9%) and uncertain pathogens in 143 (0.9%). In the multivariable model, factors associated with a positive BC were age (29 days-12-month-olds OR 1.33, 95% CI 1.06 to 1.66 and 5-18 year-olds OR 1.62, 95% CI 1.30 to 2.01 vs 1-4 year-olds), number of clinical severity signs (OR 1.29, 95% CI 1.18 to 1.40 per one sign) and hospital acquired infection (OR 3.05, 95% CI 2.30 to 4.06 vs community-acquired). Suspected diagnosis of sepsis (OR 2.09, 95% CI 1.67 to 2.61), gastrointestinal/abdominal (OR 2.36, 95% CI 1.78 to 3.13), skin and soft tissue or bone (OR 3.64, 95% CI 2.57 to 5.14) and genitourinary infection (OR 2.22, 95% CI 1.39 to 3.56) were more likely to have a positive BC, compared with respiratory infections. CONCLUSION: We confirmed the low BC yield among hospitalised children. We identified groups for which diagnostic stewardship efforts to increase BC uptake should be prioritised and others in which it could be limited in times of financial or logistic constraints.

Humans

Pneumococcal within-host diversity during colonization, transmission and treatment.

Characterizing the genetic diversity of pathogens within the host promises to greatly improve surveillance and reconstruction of transmission chains. For bacteria, it also informs our understanding of inter-strain competition and how this shapes the distribution of resistant and sensitive bacteria. Here we study the genetic diversity of Streptococcus pneumoniae within 468 infants and 145 of their mothers by deep sequencing whole pneumococcal populations from 3,761 longitudinal nasopharyngeal samples. We demonstrate that deep sequencing has unsurpassed sensitivity for detecting multiple colonization, doubling the rate at which highly invasive serotype 1 bacteria were detected in carriage compared with gold-standard methods. The greater resolution identified an elevated rate of transmission from mothers to their children in the first year of the child's life. Comprehensive treatment data demonstrated that infants were at an elevated risk of both the acquisition and persistent colonization of a multidrug-resistant bacterium following antimicrobial treatment. Some alleles were enriched after antimicrobial treatment, suggesting that they aided persistence, but generally purifying selection dominated within-host evolution. Rates of co-colonization imply that in the absence of treatment, susceptible lineages outcompeted resistant lineages within the host. These results demonstrate the many benefits of deep sequencing for the genomic surveillance of bacterial pathogens.

Child