Multiple locus VNTR analysis highlights that geographical clustering and distribution of Dichelobacter nodosus, the causal agent of footrot in sheep, correlates with inter-country movements

Dichelobacter nodosus is a Gram-negative, anaerobic bacterium and the causal agent of footrot in sheep. Multiple locus variable number tandem repeat (VNTR) analysis (MLVA) is a portable technique that involves the identification and enumeration of polymorphic tandem repeats across the genome. The aims of this study were to develop an MLVA scheme for D. nodosus suitable for use as a molecular typing tool, and to apply it to a global collection of isolates. Seventy-seven isolates selected from regions with a long history of footrot (GB, Australia) and regions where footrot has recently been reported (India, Scandinavia), were characterised. From an initial 61 potential VNTR regions, four loci were identified as usable and in combination had the attributes required of a typing method for use in bacterial epidemiology: high discriminatory power (D > 0.95), typeability and reproducibility. Results from the analysis indicate that D. nodosus appears to have evolved via recombinational exchanges and clonal diversification. This has resulted in some clonal complexes that contain isolates from multiple countries and continents; and others that contain isolates from a single geographic location (country or region). The distribution of alleles between countries matches historical accounts of sheep movements, suggesting that the MLVA technique is sufficiently specific and sensitive for an epidemiological investigation of the global distribution of D. nodosus

Raising AWaRe-ness of antimicrobial stewardship challenges in pediatric emergency care: results from the PERFORM study assessing consistency and appropriateness of antibiotic prescribing across Europe.

OBJECTIVES Optimization of antimicrobial stewardship (AMS) is key to tackling antimicrobial resistance (AMR), which is exacerbated by over-prescription of antibiotics in pediatric Emergency Departments (EDs). We described patterns of empiric antibiotic use in European EDs, and characterized appropriateness and consistency of prescribing. METHODS Between August 2016 and December 2019 febrile children attending the ED in nine European countries with suspected infection were recruited into the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management) study. Empiric systemic antibiotic use was determined in view of assigned final 'bacterial' or 'viral' phenotype. Antibiotics were classified according to WHO AWaRe. RESULTS Of 2130 febrile episodes (excluding children with non-bacterial/non-viral phenotypes), 1549 (72.7%) were assigned a 'bacterial' and 581 (27.3%) a 'viral' phenotype. A total of 1318/1549 (85.1%) episodes with a 'bacterial' and 269/581 (46.3%) with a 'viral' phenotype received empiric systemic antibiotics (first two days of admission). Of those, the majority (87.8% in 'bacterial' and 87.0% in 'viral' group) received parenteral antibiotics. The top three antibiotics prescribed were third-generation cephalosporins, penicillins and penicillin/beta-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the 'viral' group 216/269 (80.3%) received ≥ one Watch antibiotic. CONCLUSIONS Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial over-prescription of antibiotics. A significant proportion of patients with a 'viral' phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology, could significantly improve AMS

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe:a multicentre, prospective observational study

Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.</p

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

http://wrap.warwick.ac.uk Original citation: Dynamics and impact of footrot and climate on hoof horn length in 50 ewes from one farm over a period of 10 months

Dynamics and impact of footrot and climate on hoof horn length in 50 ewes from one farm over a period of 10 months. The Veterinary Journal, Volume 201 (Number 3). pp. Footrot, including interdigital dermatitis, is caused by Dichelobacter nodosus cause the majority of lameness in sheep in the UK. Lame sheep often have overgrown hoof horn but recent evidence has indicated that trimming overgrown hoof horn increases recovery time, and that routine foot trimming of the flock does not reduce the prevalence or incidence of lameness. The objectives of this study were to investigate the temporal associations between hoof horn length, footrot and climate. Fifty multiparous ewes were monitored for 10 months. On eight occasions hoof horn length, foot lesions and body condition were recorded. At the first examination, ewes were assigned to one of two treatment groups. All ewes that became lame with footrot were treated at one time point per week, either by trimming hoof horn and applying a topical antibiotic spray or with parenteral antibiotic and topical antibiotic spray. Hoof horn length in ewes at pasture varied over the year and was associated with temperature and rainfall. New cases of footrot occurred all year round and were associated with prior prevalence of footrot in the flock and prior temperature and rainfall. Overgrown hoof horn did not precede lameness but occurred once the sheep were lame. One year of prompt treatment of footrot reduced the range in hoof horn length in the sheep in both treatment groups. At the end of the study the hoof lengths of ewes in both groups were not significantly different. On this farm, hoof horn length was self-regulating in both non-lame and treated lame sheep whether trimming was part of the treatment or not and there would have been no benefit from routine foot trimming of this flock

Dynamics and impact of footrot and climate on hoof horn length in 50 ewes from one farm over a period of 10 months

Footrot and interdigital dermatitis caused by Dichelobacter nodosus cause the majority of lameness in sheep in the UK. Lame sheep often have overgrown hoof horn but recent evidence has indicated that trimming overgrown hoof horn increases recovery time, and that routine foot trimming of the flock does not reduce the prevalence or incidence of lameness. The objectives of this study were to investigate the temporal associations between hoof horn length, footrot and climate. Fifty multiparous ewes were monitored for 10 months. On eight occasions hoof horn length, foot lesions and body condition were recorded. At the first examination, ewes were assigned to one of two treatment groups. All ewes that became lame with footrot were treated at one time point per week, either by trimming hoof horn and applying a topical antibiotic spray or with parenteral antibiotic and topical antibiotic spray. Hoof horn length in ewes at pasture varied over the year and was associated with temperature and rainfall. New cases of footrot occurred all year round and were associated with prior prevalence of footrot in the flock and prior temperature and rainfall. Overgrown hoof horn did not precede lameness but occurred once the sheep were lame. One year of prompt treatment of footrot reduced the range in hoof horn length in the sheep in both treatment groups. At the end of the study the hoof lengths of ewes in both groups were not significantly different. On this farm, hoof horn length was self-regulating in both non-lame and treated lame sheep whether trimming was part of the treatment or not and there would have been no benefit from routine foot trimming of this floc