ORCID Profile
0000-0002-0594-0902
Current Organisations
Liverpool School of Tropical Medicine
,
University of Oxford
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Publisher: Oxford University Press (OUP)
Date: 28-01-2019
Publisher: Springer Science and Business Media LLC
Date: 05-07-2019
DOI: 10.1038/S41467-019-10814-9
Abstract: Streptococcus pneumoniae is the main bacterial pathogen involved in pneumonia. Pneumococcal acquisition and colonization density is probably affected by viral co-infections, the local microbiome composition and mucosal immunity. Here, we report the interactions between live-attenuated influenza vaccine (LAIV), successive pneumococcal challenge, and the healthy adult nasal microbiota and mucosal immunity using an experimental human challenge model. Nasal microbiota profiles at baseline are associated with consecutive pneumococcal carriage outcome (non-carrier, low-dense and high-dense pneumococcal carriage), independent of LAIV co-administration. Corynebacterium / Dolosigranulum -dominated profiles are associated with low-density colonization. Lowest rates of natural viral co-infection at baseline and post-LAIV influenza replication are detected in the low-density carriers. Also, we detected the fewest microbiota perturbations and mucosal cytokine responses in the low-density carriers compared to non-carriers or high-density carriers. These results indicate that the complete respiratory ecosystem affects pneumococcal behaviour following challenge, with low-density carriage representing the most stable ecological state.
Publisher: Elsevier BV
Date: 02-2020
Publisher: American Thoracic Society
Date: 05-2019
Publisher: American Society for Clinical Investigation
Date: 04-2022
DOI: 10.1172/JCI157124
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
Publisher: American Thoracic Society
Date: 15-12-2016
Publisher: American Society for Clinical Investigation
Date: 26-01-2021
Publisher: F1000 Research Ltd
Date: 10-02-2023
DOI: 10.12688/WELLCOMEOPENRES.18767.1
Abstract: Background: Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns. Methods: A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases and Google Scholar to search citations in selected manuscripts. The final search was conducted 3 rd February 2022. Inclusion criteria: adults ≥18 years old administration of live mycobacteria and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies studies with no primary data no administration of live mycobacteria retrospective cohort studies case-series and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings. Results: The search identified 1,388 titles for review of these 90 were reviewed for inclusion and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified Mycobacteria tuberculosis is the most tantalising prospect of discovery breakthrough. Conclusions: The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations. Registration: PROSPERO ( CRD42022302785 21 January 2022).
Publisher: American Thoracic Society
Date: 03-2021
Publisher: American Society for Clinical Investigation
Date: 16-09-2019
DOI: 10.1172/JCI128865
Publisher: American Thoracic Society
Date: 12-2022
Publisher: European Respiratory Society (ERS)
Date: 10-2018
Publisher: Cold Spring Harbor Laboratory
Date: 29-04-2020
DOI: 10.1101/2020.04.23.20077073
Abstract: Pneumococcal colonisation is key to the pathogenesis of invasive disease, but is also immunogenic in young adults, protecting against re-colonisation. Colonisation is rarely detected in older adults, despite high rates of pneumococcal disease. To establish experimental human pneumococcal colonisation in healthy adults aged 50—84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonisation against autologous strain rechallenge. Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B, 80,000CFU in each nostril). Colonisation was determined by bacterial culture of nasal wash, serum anti-6B capsular IgG responses by ELISA, and anti-protein immune responses by multiplex electrochemiluminescence. Experimental colonisation was established in 39% of participants (25/64) with no adverse events. Colonisation occurred in 47% (9/19) of participants aged 50—59 compared with 21% (3/14) in those aged ≥70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonisation. Colonisation did not confer serotype-specific immune boosting: GMT (95% CI) 2.7μg/mL (1.9—3.8) pre-challenge versus 3.0 (1.9—4.7) four weeks post-colonisation (p = 0.53). Furthermore, pneumococcal challenge without colonisation led to a drop in specific antibody levels from 2.8μg/mL (2.0—3.9) to 2.2μg/mL (1.6—3.0) post-challenge (p = 0.006). Anti-protein antibody levels increased following successful colonisation. Rechallenge with the same strain after a median of 8.5 months (IQR 6.7—10.1) led to recolonisation in 5/16 (31%). In older adults, experimental pneumococcal colonisation is feasible and safe, but demonstrates different immunological outcomes compared with younger adults in previous studies.
Publisher: Wiley
Date: 14-09-2017
DOI: 10.1111/COA.12956
Abstract: Saline irrigation of the nasal cavity and paranasal sinuses has a recognised role in the management of chronic rhinosinusitis. However, bacterial recontamination of irrigation bottles through backflow from the sinonasal cavity is a concern in recurrent sinus cavity infections. While patients are encouraged to clean the irrigation bottles regularly, there remains significant concern that the use of contaminated bottles may perpetuate chronic rhinosinusitis. This study assesses the optimal microwave duration to achieve decontamination for each irrigation bottle component part (reservoir, tube and nozzle) using a standard, commercially available microwave. In addition, the irrigation fluid was also tested for contamination after each microwave cycle. Laboratory-based experimental study. No patients were involved in this study. The percentage in vitro decontamination of the bottles' components was determined following 30, 60, 90, 120, 150 seconds of microwave cycles. Complete decontamination of the bottles was not achieved at any of the tested microwave cycles. Levels of decontamination differed for the different bottle components, and the greatest degree of decontamination for all bottle components occurred at 90 seconds. Although higher levels of decontamination were observed at microwave durations exceeding 90 seconds, this was at the expense of thermal degradation and deformation of the reservoir plastic component of the irrigation bottle. Similarly, lowest contamination of irrigation fluid was observed at 120 seconds. This study highlights the importance of establishing precise decontamination procedures and recommends a microwave cycle of 90 seconds for optimal decontamination.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2018
Publisher: American Thoracic Society
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 16-07-2019
DOI: 10.1038/S41467-019-11005-2
Abstract: Control of Streptococcus pneumoniae colonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving herd protection. Here, we use an experimental human pneumococcal carriage model (EHPC) to show that S. pneumoniae colonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epithelium shaped the host transcriptomic response in vitro. Using epithelial modules from a human epithelial cell model that recapitulates our in vivo findings, comprising of innate signalling and regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. Our results indicate that, rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances inflammatory and innate immune responses associated with clearance.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Daniela M Ferreira.