Publications by authors named "Robert B Dorey"

6 Publications

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Manipulating the infant respiratory microbiomes to improve clinical outcomes: A review of the literature.

J Infect 2021 Mar 19. Epub 2021 Mar 19.

NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton, Tremona Road, SO166YD Southampton, United Kingdom; Faculty of Medicine and Institute of for Life Sciences, F level, South Academic Block, University Hospital Southampton, Tremona Road, SO166YD Southampton, United Kingdom.

Background: The association between infant respiratory microbiota and disease (including respiratory tract infections and asthma) is increasingly recognised, although the mechanism remains unclear. Respiratory infections and asthma account for a large proportion of infant morbidity and mortality, so the possibility of preventing disease or modifying clinical outcomes by manipulating microbiome development warrants investigation.

Objectives And Methods: We identified studies that investigated the efficacy of live bacteria (probiotics or human challenge) or their substrates to modify respiratory colonisation or clinical outcomes in infants.

Eligibility Criteria: Interventional studies involving infants under one year of age, administration of live bacteria or their substrates, and outcome measures including bacterial colonisation, microbiome profile, or respiratory disease phenotypes.

Results And Limitations: Some bacterial interventions can reduce infant respiratory infections, although none have been shown to reduce asthma incidence. The literature is heterogeneous in design and quality, precluding meaningful meta-analysis.

Conclusions: Upper respiratory tract infant microbiome manipulation may alter outcomes in respiratory tract infection, but further well-conducted research is needed to confirm this. Improved regulation of proprietary bacterial products is essential for further progress.
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http://dx.doi.org/10.1016/j.jinf.2021.03.012DOI Listing
March 2021

Influenza vaccination: protecting the most vulnerable.

Eur Respir Rev 2021 Mar 13;30(159). Epub 2021 Jan 13.

School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

Influenza virus infection causes seasonal epidemics and occasional pandemics, leading to huge morbidity and mortality worldwide. Vaccination against influenza is needed annually as protection from constantly mutating strains is required. Groups at high risk of poor outcomes include the elderly, the very young, pregnant women and those with chronic health conditions. However, vaccine effectiveness in the elderly is generally poor due to immunosenescence and may be altered due to "original antigenic sin". Strategies to overcome these challenges in the elderly include high-dose or adjuvant vaccines. Other options include vaccinating healthcare workers and children as this reduces community-level influenza transmission. Current guidelines in the UK are that young children receive a live attenuated nasal spray vaccine, adults aged >65 years receive an adjuvanted trivalent inactivated vaccine and adults aged <65 years with comorbidities receive a quadrivalent inactivated vaccine. The goal of a universal influenza vaccine targeting conserved regions of the virus and avoiding the need for annual vaccination is edging closer with early-phase trials under way.
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http://dx.doi.org/10.1183/16000617.0258-2020DOI Listing
March 2021

The infant pharyngeal microbiomes: origin, impact and manipulation.

Curr Opin Infect Dis 2020 12;33(6):548-555

Faculty of Medicine and Institute for Life Sciences, University of Southampton.

Purpose Of Review: There has been an exponential increase in research into infant microbiome evolution, and it appears that pharyngeal microbiota are associated with clinical phenotypes (e.g. infection and asthma). Although broad consensus views are emerging, significant challenges and uncertainties remain.

Recent Findings: Infant pharyngeal microbiome research is limited by low biomass, high temporal diversity and lack of agreed standards for sampling, DNA sequencing and taxonomic reporting. Analysis of amplicon sequence variants and improved cost and availability of whole-genome sequencing are promising options for improving taxonomic resolution of such studies. Infant respiratory microbiomes arise, at least in part, from maternal flora (e.g. the respiratory tract and breastmilk), and are associated with environmental and clinical factors (e.g. mode of feeding and delivery, siblings, daycare attendance, birth season and antibiotic usage). Interventional research to modify the infant pharyngeal microbiota has recently been reported, using dietary supplements.

Summary: Further work is needed to improve characterization of the infant pharyngeal microbiomes, including routes of bacterial acquisition, role of environmental factors and associations with disease phenotypes. Methodological standards are desirable to facilitate more reproducible, comparable research. Improved understanding may enable manipulation of infant pharyngeal microbiota to improve clinical outcomes.
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http://dx.doi.org/10.1097/QCO.0000000000000691DOI Listing
December 2020

Neuroinflammation in dementia with Lewy bodies: a human post-mortem study.

Transl Psychiatry 2020 08 3;10(1):267. Epub 2020 Aug 3.

Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). It is now established that cerebral inflammation has a key role in the aetiology and progression of AD, but this has yet to be confirmed in DLB. We aimed to determine the neuroinflammatory profile in the cerebral cortex of a large cohort of DLB cases. Thirty post-mortem confirmed DLB cases and twenty-nine matched controls were immunolabelled (Brodmann area 21) and quantified for: neuropathology-αSYN, Aβ, P-tau; microglial phenotype-Iba1, HLA-DR, CD68, FcƴR (CD64, CD32a, CD32b, CD16); presence of T lymphocytes-CD3; and anti-inflammatory markers-IL4R, CHI3L1. Status spongiosis, as a marker of neuropil degeneration, was quantified using Haematoxylin and Eosin staining. We found no significant difference between groups in protein load for Iba1, HLA-DR, CD68, CD64, CD32b, IL4R, or CHI3L1, despite increased neuropathology in DLB. CD32a load was significantly lower, and CD16 load higher, in DLB compared with controls. There was no difference in status spongiosis between groups. Significantly more DLB cases than controls showed T-lymphocyte recruitment. Overall, we conclude that microglial activation is not a prominent feature of DLB, and that this may be associated with the relatively modest neuropil degeneration observed in DLB. Our findings, based on the largest post-mortem cohort to date exploring neuroinflammation in DLB, demonstrate a dissociation between protein deposition, neurodegeneration and microglial activation. The relative preservation of cortical structures in DLB suggests the dementia could be more amenable to potential therapies.
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http://dx.doi.org/10.1038/s41398-020-00954-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400566PMC
August 2020

High frequency of paediatric facial nerve palsy due to Lyme disease in a geographically endemic region.

Int J Pediatr Otorhinolaryngol 2020 May 25;132:109905. Epub 2020 Jan 25.

NIHR Southampton Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Paediatric Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.

Introduction: Idiopathic facial nerve palsy (FNP) is an uncommon but important presentation in children, with Lyme disease known to be a common cause. The UK county of Hampshire is a high incidence area of Lyme disease. We conducted a retrospective review of the investigation and management of paediatric FNP at a large University hospital, including serologic testing and treatment of Lyme disease.

Methods: We conducted a retrospective chart review of children under 18 presenting between January 1st 2010 and December 31st 2017 with a diagnosis of FNP. Patients with clear non-Lyme aetiology at presentation were excluded. Data was collected on demographics, initial presentation, investigations including Lyme serology, and management.

Results: A total of 93 children were identified, with an even proportion of male to female and median age 9.3 years (IQR 4.6-12 years). A history of rash was present in 5.4%, tick bite in 14% and recent travel to, or residence in the New Forest in 22.6%. Lyme serology was performed in 81.7% of patients, of which 29% were positive. Antibiotics were prescribed for 73.1% of patients, oral steroids for 44% and aciclovir for 17.2%.

Conclusion: Lyme disease is a significant cause of FNP in this endemic area of the UK, and there was a large degree of variability in management prior to national guideline publication. Areas with endemic Lyme disease should consider introducing local guidelines supporting routine investigation and management for FNP, including empiric treatment for Lyme disease in accordance with NICE guidelines to improve care and reduce variability.
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http://dx.doi.org/10.1016/j.ijporl.2020.109905DOI Listing
May 2020

The nonpathogenic commensal Neisseria: friends and foes in infectious disease.

Curr Opin Infect Dis 2019 10;32(5):490-496

Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.

Purpose Of Review: Nonpathogenic commensal Neisseria are rarely considered in the clinical setting despite evidence that they can cause invasive opportunistic infections. In contrast, they may offer protection against pathogenic Neisseria, and such relationships are being actively explored in experimental studies.

Recent Findings: Recent case reports are presented of invasive infection caused by nonpathogenic Neisseria in patients on novel biologic therapies. On the other hand, Neisseria lactamica, a nonpathogenic commensal, has been shown in human challenge studies to inhibit colonization by Neisseria meningitidis. Experimental mouse models have also explored the inhibitory effects of nonpathogenic Neisseria on Neisseria gonnhoreae infection. Cutting-edge advances in metagenomics and microbiomics are being used to understand the mechanisms underpinning these effects.

Summary: Clinicians should have increased awareness of nonpathogenic Neisseria. First, as new immunomodulating therapies become licenced, the interactions that maintain balance between commensals and their human hosts may be altered. Second, these bacteria are showing promise in their capacity to exclude pathogenic Neisseria species from their anatomical niches.
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http://dx.doi.org/10.1097/QCO.0000000000000585DOI Listing
October 2019