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Article ; Online: Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol

Maia Lesosky / Konstantinos Liatsikos / Stephen B Gordon / Kelly Davies / Phoebe Hazenberg / Angela Hyder-Wright / Ryan E Robinson / Britta Urban / Elena Mitsi / Carla Solorzano / Daniela M Ferreira / Madlen Farrar / Ashleigh Howard / Andrea M Collins / Jaye Brunning / Hannah Fleet / Amy Bettam / Tinashe Kenny-Nyazika / Dima El Safadi

BMJ Open, Vol 14, Iss

dose ranging and reproducibility in a healthy volunteer population (challenge 3)

2024 Volume 1

Abstract: Introduction Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation ... ...

Abstract	Introduction Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation rates, understanding acquired immunity, and testing vaccines in a cost-effective manner. To enhance the development of effective pneumococcal vaccines against SPN3, we aim to develop a new relevant and safe SPN3 EHPC model with high attack rates which could be used to test vaccines using small sample size.Methods and analysis This is a human challenge study to establish a new SPN3 EHPC model, consisting of two parts. In the dose-ranging/safety study, cohorts of 10 healthy participants will be challenged with escalating doses of SPN3. If first challenge does not lead into colonisation, participants will receive a second challenge 2 weeks after. Experimental nasopharyngeal (NP) colonisation will be determined using nasal wash sampling. Using the dose that results in ≥50% of participants being colonised, with a high safety profile, we will complete the cohort with another 33 participants to check for reproducibility of the colonisation rate. The primary outcome of this study is to determine the optimal SPN3 dose and inoculation regime to establish the highest rates of NP colonisation in healthy adults. Secondary outcomes include determining density and duration of experimental SPN3 NP colonisation and characterising mucosal and systemic immune responses to SPN3 challenge.Ethics and dissemination This study is approved by the NHS Research and Ethics Committee (reference 22/NW/0051). Findings will be published in peer-reviewed journals and reports will be made ...
Keywords	Medicine ; R
Subject code	650
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Surveillance towards preventing paediatric incidence of respiratory syncytial virus attributable respiratory tract infection in primary and secondary/tertiary healthcare settings in Merseyside, Cheshire and Bristol, UK

Adam Finn / David Lewis / James Dodd / Matthew Taylor / Maia Lesosky / Paul Stephen McNamara / Helen Hill / Emma Carter / Kelly Davies / Fred Fyles / Carla Solorzano / Daniela M Ferreira / Gregory Duncan / Lauren McLellan / Mathieu Bangert / Natalya Vassilouthis / Andrea M Collins

BMJ Open Respiratory Research, Vol 10, Iss

2023 Volume 1

Abstract: Introduction Respiratory syncytial virus (RSV) is a common respiratory virus, particularly affecting children, and can cause respiratory infections such as croup and bronchiolitis. The latter is a leading cause of paediatric hospitalisation within the UK. ...

Abstract	Introduction Respiratory syncytial virus (RSV) is a common respiratory virus, particularly affecting children, and can cause respiratory infections such as croup and bronchiolitis. The latter is a leading cause of paediatric hospitalisation within the UK. Children <3 years of age and/or with underlying health conditions are more vulnerable to severe RSV infection.There are currently limited data on the incidence of laboratory-confirmed RSV, particularly within primary care settings and outside the typical ‘RSV season’, which in the Northern hemisphere tends to coincide with winter months. There is also a lack of data on the health economic impact of RSV infection on families and healthcare systems.This observational surveillance study aims to collect data on the incidence of laboratory-confirmed RSV-attributable respiratory tract infection (RTI) in children aged <3 years presenting to primary, secondary or tertiary care; it also aims to estimate the health economic and quality of life impact of RSV-attributable infection in this cohort. Such data will contribute to informing public health strategies to prevent RSV-associated infection, including use of preventative medications.Methods and analysis Parents/carers of children <3 years of age with RTI symptoms will consent for a respiratory sample (nasal swab) to be taken. Laboratory PCR testing will assess for the presence of RSV and/or other pathogens. Data will be obtained from medical records on demographics, comorbidities, severity of infection and hospitalisation outcomes. Parents will complete questionnaires on the impact of ongoing infection symptoms at day 14 and 28 following enrolment. The primary outcome is incidence of laboratory-confirmed RSV in children <3 years presenting to primary, secondary or tertiary care with RTI symptoms leading to health-seeking behaviours. Recruitment will be carried out from December 2021 to March 2023, encompassing two UK winter seasons and intervening months.Ethics and dissemination Ethical approval has been ...
Keywords	Medicine ; R ; Diseases of the respiratory system ; RC705-779
Subject code	360
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Women’s perspectives of small-scale fisheries and environmental change in Chilika lagoon, India

Khan, Fatima Noor / Andrea M. Collins / Prateep Kumar Nayak / Derek Armitage

Maritime studies. 2018 Oct., v. 17, no. 2

2018

Abstract: This article investigates the gendered implications of environmental change using case studies of two small-scale fishing communities in Chilika lagoon, India. We undertake an intersectional analysis that examines dynamics between groups of fisherwomen ... ...

Abstract	This article investigates the gendered implications of environmental change using case studies of two small-scale fishing communities in Chilika lagoon, India. We undertake an intersectional analysis that examines dynamics between groups of fisherwomen in relation to social-ecological change. We focus specifically on (1) fisherwomen’s perspectives about the key drivers of change (e.g., natural disasters and aquaculture) within the social and ecological system of Chilika lagoon; (2) how environmental change is impacting the livelihoods and coping responses of fisherwomen; and (3) how fisherwomen communities are adapting to the ongoing process of change, highlighting in particular the gendered dimensions of out-migration. Our findings demonstrate that fisherwomen’s roles and identities are not static and that the impacts of environmental change vary for different groups of fisherwomen. We find that gender intersects with caste, income, geographic location, age, and household membership to create heterogeneous experiences and knowledge that reflects the complexities associated with gender and environmental change. With specific regard to the increase in fisherwomen out-migrating, we show that responses and adaptations to environmental change have gender-differentiated impacts and challenges.
Keywords	aquaculture ; case studies ; disasters ; fisheries ; gender ; income ; livelihood ; women ; India
Language	English
Dates of publication	2018-10
Size	p. 145-154.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	2705697-1
ISSN	2212-9790 ; 1872-7859
ISSN (online)	2212-9790
ISSN	1872-7859
DOI	10.1007/s40152-018-0100-1
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Influence of sex, season and environmental air quality on experimental human pneumococcal carriage acquisition

Katerina S. Cheliotis / Christopher P. Jewell / Carla Solórzano / Britta Urban / Andrea M. Collins / Elena Mitsi / Sherin Pojar / Elissavet Nikolaou / Esther L. German / Jesús Reiné / Stephen B. Gordon / Simon P. Jochems / Jamie Rylance / Daniela M. Ferreira

ERJ Open Research, Vol 8, Iss

a retrospective cohort analysis

2022 Volume 2

Abstract: Streptococcus pneumoniae (pneumococcus) is the most commonly identified bacterial cause of pneumonia and the leading infectious cause of death in children under 5 years of age worldwide. Pneumococcal disease follows a seasonal pattern with increased ... ...

Abstract	Streptococcus pneumoniae (pneumococcus) is the most commonly identified bacterial cause of pneumonia and the leading infectious cause of death in children under 5 years of age worldwide. Pneumococcal disease follows a seasonal pattern with increased incidence during winter. Pneumonia burden is also associated with poor air quality. Nasopharyngeal carriage of the bacterium is a pre-requisite of invasive disease. We aimed to determine if susceptibility to nasopharyngeal pneumococcal carriage varied by season and which environmental factors might explain such variation. We also evaluated the influence of sex on susceptibility of carriage. We collated data from five studies in which human volunteers underwent intranasal pneumococcal challenge. Generalised linear mixed-effects models were used to identify factors associated with altered risk of carriage acquisition, specifically climate and air-quality data. During 2011–2017, 374 healthy adults were challenged with type 6B pneumococcus. Odds of carriage were significantly lower in males (OR, 0.61; 95% CI, 0.40–0.92; p=0.02), and higher with cooler temperatures (OR, 0.79; 95% CI, 0.63–0.99; p=0.04). Likelihood of carriage was also associated with lower concentrations of local fine particulate matter concentrations (PM2.5) and increased local rainfall. In contrast to epidemiological series, experimental challenge allowed us to test propensity to acquisition during controlled exposures; immunological explanations for sex and climatic differences should be sought.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 14

Abstract: Abstract Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, the capacity of peripheral vaccination to generate sustained immunity in the lung mucosa, and how this is ... ...

Abstract	Abstract Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, the capacity of peripheral vaccination to generate sustained immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Here we show using bronchoalveolar lavage samples that donors with history of both infection and vaccination have more airway mucosal SARS-CoV-2 antibodies and memory B cells than those only vaccinated. Infection also induces populations of airway spike-specific memory CD4+ and CD8+ T cells that are not expanded by vaccination alone. Airway mucosal T cells induced by infection have a distinct hierarchy of antigen specificity compared to the periphery. Spike-specific T cells persist in the lung mucosa for 7 months after the last immunising event. Thus, peripheral vaccination alone does not appear to induce durable lung mucosal immunity against SARS-CoV-2, supporting an argument for the need for vaccines targeting the airways.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Participant perceptions and experiences of a novel community-based respiratory longitudinal sampling method in Liverpool, UK

PLoS ONE, Vol 18, Iss 11, p e

A mixed methods feasibility study.

2023 Volume 0294133

Abstract: Longitudinal, community-based sampling is important for understanding prevalence and transmission of respiratory pathogens. Using a minimally invasive sampling method, the FAMILY Micro study monitored the oral, nasal and hand microbiota of families for 6 ...

Abstract	Longitudinal, community-based sampling is important for understanding prevalence and transmission of respiratory pathogens. Using a minimally invasive sampling method, the FAMILY Micro study monitored the oral, nasal and hand microbiota of families for 6 months. Here, we explore participant experiences and opinions. A mixed methods approach was utilised. A quantitative questionnaire was completed after every sampling timepoint to report levels of discomfort and pain, as well as time taken to collect samples. Participants were also invited to discuss their experiences in a qualitative structured exit interview. We received questionnaires from 36 families. Most adults and children >5y experienced no pain (94% and 70%) and little discomfort (73% and 47% no discomfort) regardless of sample type, whereas children ≤5y experienced variable levels of pain and discomfort (48% no pain but 14% hurts even more, whole lot or worst; 38% no discomfort but 33% moderate, severe, or extreme discomfort). The time taken for saliva and hand sampling decreased over the study. We conducted interviews with 24 families. Families found the sampling method straightforward, and adults and children >5y preferred nasal sampling using a synthetic absorptive matrix over nasopharyngeal swabs. It remained challenging for families to fit sampling into their busy schedules. Adequate fridge/freezer space and regular sample pick-ups were found to be important factors for feasibility. Messaging apps proved extremely effective for engaging with participants. Our findings provide key information to inform the design of future studies, specifically that self-sampling at home using minimally invasive procedures is feasible in a family context.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pneumococcal colonisation is an asymptomatic event in healthy adults using an experimental human colonisation model.

Ashleigh Trimble / Victoria Connor / Ryan E Robinson / Daniella McLenaghan / Carole A Hancock / Duolao Wang / Stephen B Gordon / Daniela M Ferreira / Angela D Wright / Andrea M Collins

PLoS ONE, Vol 15, Iss 3, p e

2020 Volume 0229558

Abstract: Introduction Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported pneumococcal colonisation to be a symptomatic event and described a relationship between symptom ... ...

Abstract	Introduction Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported pneumococcal colonisation to be a symptomatic event and described a relationship between symptom severity/frequency and colonisation density. The evidence for this in adults is lacking in the literature. This study uses the experimental human pneumococcal challenge (EHPC) model to explore whether pneumococcal colonisation is a symptomatic event in healthy adults. Methods Healthy participants aged 18-50 were recruited and inoculated intra-nasally with either Streptococcus pneumoniae (serotypes 6B, 23F) or saline as a control. Respiratory viral swabs were obtained prior to inoculation. Nasal and non-nasal symptoms were then assessed using a modified Likert score between 1 (no symptoms) to 7 (cannot function). The rate of symptoms reported between the two groups was compared and a correlation analysis performed. Results Data from 54 participants were analysed. 46 were inoculated with S. pneumoniae (29 with serotype 6B, 17 with serotype 23F) and 8 received saline (control). In total, 14 became experimentally colonised (30.4%), all of which were inoculated with serotype 6B. There was no statistically significant difference in nasal (p = 0.45) or non-nasal symptoms (p = 0.28) between the inoculation group and the control group. In those who were colonised there was no direct correlation between colonisation density and symptom severity. In the 22% (12/52) who were co-colonised, with pneumococcus and respiratory viruses, there was no statistical difference in either nasal or non-nasal symptoms (virus positive p = 0.74 and virus negative p = 1.0). Conclusion Pneumococcal colonisation using the EHPC model is asymptomatic in healthy adults, regardless of pneumococcal density or viral co-colonisation.
Keywords	Medicine ; R ; Science ; Q
Subject code	150
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers

Naomi F Walker / Rachel L Byrne / Ashleigh Howard / Elissavet Nikolaou / Madlen Farrar / Sharon Glynn / Katerina S Cheliotis / Ana I Cubas Atienzar / Kelly Davies / Jesús Reiné / Zalina Rashid-Gardner / Esther L German / Carla Solórzano / Tess Blandamer / Lisa Hitchins / Christopher Myerscough / Bradford D Gessner / Elizabeth Begier / Andrea M Collins /

Mike Beadsworth / Stacy Todd / Helen Hill / Catherine F Houlihan / Eleni Nastouli / Emily R Adams / Elena Mitsi / Daniela M Ferreira / SAFER investigators

PLoS ONE, Vol 18, Iss 1, p e

An observational cohort study.

2023 Volume 0280908

Abstract: Background The SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the United Kingdom National Health Service (NHS). We conducted an observational cohort study of SARS-CoV-2 infection in frontline healthcare ... ...

Abstract	Background The SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the United Kingdom National Health Service (NHS). We conducted an observational cohort study of SARS-CoV-2 infection in frontline healthcare workers (HCW) working in an acute NHS Trust during the first wave of the pandemic, to answer emerging questions surrounding SARS-CoV-2 infection, diagnosis, transmission and control. Methods Using self-collected weekly saliva and twice weekly combined oropharyngeal/nasopharyngeal (OP/NP) samples, in addition to self-assessed symptom profiles and isolation behaviours, we retrospectively compared SARS-CoV-2 detection by RT-qPCR of saliva and OP/NP samples. We report the association with contemporaneous symptoms and isolation behaviour. Results Over a 12-week period from 30th March 2020, 40·0% (n = 34/85, 95% confidence interval 31·3-51·8%) HCW had evidence of SARS-CoV-2 infection by surveillance OP/NP swab and/or saliva sample. Symptoms were reported by 47·1% (n = 40) and self-isolation by 25·9% (n = 22) participants. Only 44.1% (n = 15/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of a positive result and only 29·4% (n = 10/34) reported self-isolation periods. Overall agreement between paired saliva and OP/NP swabs was 93·4% (n = 211/226 pairs) but rates of positive concordance were low. In paired samples with at least one positive result, 35·0% (n = 7/20) were positive exclusively by OP/NP swab, 40·0% (n = 8/20) exclusively by saliva and in only 25·0% (n = 5/20) were the OP/NP and saliva result both positive. Conclusions HCW are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections. Without routine asymptomatic SARS-CoV-2 screening, it is likely that HCW with SARS-CoV-2 infection would continue to attend work. Saliva, in addition to OP/NP swab testing, facilitated ascertainment of symptomatic and asymptomatic SARS-CoV-2 infections. Combined saliva and OP/NP swab ...
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The nose is the best niche for detection of experimental pneumococcal colonisation in adults of all ages, using nasal wash

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 9

Abstract: Abstract Previous studies have suggested that the pneumococcal niche changes from the nasopharynx to the oral cavity with age. We use an Experimental Human Pneumococcal Challenge model to investigate pneumococcal colonisation in different anatomical ... ...

Abstract	Abstract Previous studies have suggested that the pneumococcal niche changes from the nasopharynx to the oral cavity with age. We use an Experimental Human Pneumococcal Challenge model to investigate pneumococcal colonisation in different anatomical niches with age. Healthy adults (n = 112) were intranasally inoculated with Streptococcus pneumoniae serotype 6B (Spn6B) and were categorised as young 18–55 years (n = 57) or older > 55 years (n = 55). Colonisation status (frequency and density) was determined by multiplex qPCR targeting the lytA and cpsA-6A/B genes in both raw and culture-enriched nasal wash and oropharyngeal swab samples collected at 2-, 7- and 14-days post-exposure. For older adults, raw and culture-enriched saliva samples were also assessed. 64% of NW samples and 54% of OPS samples were positive for Spn6B in young adults, compared to 35% of NW samples, 24% of OPS samples and 6% of saliva samples in older adults. Many colonisation events were only detected in culture-enriched samples. Experimental colonisation was detected in 72% of young adults by NW and 63% by OPS. In older adults, this was 51% by NW, 36% by OPS and 9% by saliva. The nose, as assessed by nasal wash, is the best niche for detection of experimental pneumococcal colonisation in both young and older adults.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pneumococcal colonization impairs mucosal immune responses to live attenuated influenza vaccine

Beatriz F. Carniel / Fernando Marcon / Jamie Rylance / Esther L. German / Seher Zaidi / Jesus Reiné / Edessa Negera / Elissavet Nikolaou / Sherin Pojar / Carla Solórzano / Andrea M. Collins / Victoria Connor / Debbie Bogaert / Stephen B. Gordon / Helder I. Nakaya / Daniela M. Ferreira / Simon P. Jochems / Elena Mitsi

JCI Insight, Vol 6, Iss

2021 Volume 4

Abstract: Influenza virus infections affect millions of people annually, and current available vaccines provide varying rates of protection. However, the way in which the nasal microbiota, particularly established pneumococcal colonization, shape the response to ... ...

Abstract	Influenza virus infections affect millions of people annually, and current available vaccines provide varying rates of protection. However, the way in which the nasal microbiota, particularly established pneumococcal colonization, shape the response to influenza vaccination is not yet fully understood. In this study, we inoculated healthy adults with live Streptococcus pneumoniae and vaccinated them 3 days later with either tetravalent-inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). Vaccine-induced immune responses were assessed in nose, blood, and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, experimentally induced pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared with either the TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. Therefore, nasopharyngeal pneumococcal colonization may affect LAIV efficacy.
Keywords	Immunology ; Vaccines ; Medicine ; R
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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