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248 result(s) for "Collins, Andrea M"
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Gender and the Global Land Grab
Since the year 2000, millions of hectares of land in the Global South have been acquired by foreign investors for large-scale agricultural projects, displacing and disrupting rural communities. Women are especially disadvantaged by the global land grab: they are less likely to inherit, control, or make decisions over land, but often need land to support themselves, their families, and their communities. While international organizations have developed global guidelines to improve land governance, tensions still run high as the current policies fall short. Gender and the Global Land Grab introduces a feminist conceptual framework to analyze land governance policy around the world. Andrea Collins shows how gender norms, biases, and expectations shape land politics at different levels of governance. Drawing on examples from sub-Saharan Africa and with an in-depth case study of land politics in Tanzania, the book assesses guidelines developed by institutions such as the Food and Agriculture Organization of the United Nations and the World Bank to highlight essential considerations for developing and implementing gender-sensitive policy. Illustrating how gender shapes resource policy across all levels of political activity, Gender and the Global Land Grab provides valuable tools for transforming global policymaking.
Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination
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. Evidence from animal models suggest a vital role for mucosal vaccination in inducing protection from coronavirus infection. Here the authors examine the B and T cell responses at the lower airways, and contrast humoral and cellular immunity of people after infection and vaccination.
Saliva Alternative to Upper Respiratory Swabs for SARS-CoV-2 Diagnosis
PCR of upper respiratory specimens is the diagnostic standard for severe acute respiratory syndrome coronavirus 2 infection. However, saliva sampling is an easy alternative to nasal and throat swabbing. We found similar viral loads in saliva samples and in nasal and throat swab samples from 110 patients with coronavirus disease.
First Human Challenge Testing of a Pneumococcal Vaccine. Double-Blind Randomized Controlled Trial
Abstract Rationale New vaccines are urgently needed to protect the vulnerable from bacterial pneumonia. Clinical trials of pneumonia vaccines are slow and costly, requiring tens of thousands of patients. Studies of pneumococcal vaccine efficacy against colonization have been proposed as a novel method to down-select between vaccine candidates. Objectives Using our safe and reproducible experimental human pneumococcal colonization model, we aimed to determine the effect of 13-valent pneumococcal conjugate vaccine (PCV) on colonization. Methods A total of 100 healthy participants aged 18–50 years were recruited into this double-blind randomized placebo-controlled trial. They were randomly assigned to PCV (n = 49) or hepatitis A (control, n = 50) vaccination and inoculated with 80,000 CFU/100 μl of Streptococcus pneumoniae (6B) per naris. Measurements and Main Results Participants were followed up for 21 days to determine pneumococcal colonization by culture of nasal wash. The PCV group had a significantly reduced rate of 6B colonization (10% [5 of 48]) compared with control subjects (48% [23 of 48]) (risk ratio, 0.22; confidence interval, 0.09–0.52; P < 0.001). Density of colonization was reduced in the PCV group compared with the control group following inoculation. The area under the curve (density vs. day) was significantly reduced in the PCV compared with control group (geometric mean, 259 vs. 11,183; P = 0.017). Conclusions PCV reduced pneumococcal colonization rate, density, and duration in healthy adults. The experimental human pneumococcal colonization model is a safe, cost-effective, and efficient method to determine the protective efficacy of new vaccines on pneumococcal colonization; PCV provides a gold standard against which to test these novel vaccines. Clinical trial registered with ISRCTN: 45340436.
Participant perceptions and experiences of a novel community-based respiratory longitudinal sampling method in Liverpool, UK: A mixed methods feasibility study
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.
Pneumococcal colonisation is an asymptomatic event in healthy adults using an experimental human colonisation model
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. 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. 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). Pneumococcal colonisation using the EHPC model is asymptomatic in healthy adults, regardless of pneumococcal density or viral co-colonisation.
Comprehensive review of safety in Experimental Human Pneumococcal Challenge
Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies. A single-centre review of all EHPC studies performed 2011-2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation. In 1416 individuals (median age 21, IQR 20-25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28-2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety. No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated. Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.
Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage
Abstract Rationale We have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition after rechallenge with a homologous strain. Objectives To investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition using a heterologous challenge model. Methods We identified healthy volunteers that were naturally colonized with pneumococcus and, after clearance of their natural carriage episode, challenged them with a heterologous 6B strain. In another cohort of volunteers we assessed 6BPS-specific, PspA-specific, and PspC-specific IgG and IgA plasma and memory B-cell populations before and 7, 14, and 35 days after experimental pneumococcal inoculation. Measurements and Main Results Heterologous challenge with 6B resulted in 50% carriage among volunteers with previous natural pneumococcal carriage. Protection from carriage was associated with a high number of circulating 6BPS IgG–secreting memory B cells at baseline. There were no associations between protection from carriage and baseline levels of 6BPS IgG in serum or nasal wash, PspA-specific, or PspC-specific memory B cells or plasma cells. In volunteers who did not develop carriage, the number of circulating 6BPS memory B cells decreased and the number of 6BPS plasma cells increased postinoculation. Conclusions Our data indicate that naturally acquired PS-specific memory B cells, but not levels of circulating IgG at time of pneumococcal exposure, are associated with protection against carriage acquisition.
Experimental Human Pneumococcal Carriage Augments IL-17A-dependent T-cell Defence of the Lung
Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4(+) T-cells (Th-17 cells) are essential for clearance of pneumococci from the nasopharynx. Pneumococcal-responding IL-17A-secreting CD4(+) T-cells have not been described in the adult human lung and it is unknown whether they can be elicited by carriage and protect the lung from pneumococcal infection. We investigated the direct effect of experimental human pneumococcal nasal carriage (EHPC) on the frequency and phenotype of cognate CD4(+) T-cells in broncho-alveolar lavage and blood using multi-parameter flow cytometry. We then examined whether they could augment ex vivo alveolar macrophage killing of pneumococci using an in vitro assay. We showed that human pneumococcal carriage leads to a 17.4-fold (p = 0.007) and 8-fold (p = 0.003) increase in the frequency of cognate IL-17A(+) CD4(+) T-cells in BAL and blood, respectively. The phenotype with the largest proportion were TNF(+)/IL-17A(+) co-producing CD4(+) memory T-cells (p<0.01); IFNγ(+) CD4(+) memory T-cells were not significantly increased following carriage. Pneumococci could stimulate large amounts of IL-17A protein from BAL cells in the absence of carriage but in the presence of cognate CD4(+) memory T-cells, IL-17A protein levels were increased by a further 50%. Further to this we then show that alveolar macrophages, which express IL-17A receptors A and C, showed enhanced killing of opsonised pneumococci when stimulated with rhIL-17A (p = 0.013). Killing negatively correlated with RC (r = -0.9, p = 0.017) but not RA expression. We conclude that human pneumococcal carriage can increase the proportion of lung IL-17A-secreting CD4(+) memory T-cells that may enhance innate cellular immunity against pathogenic challenge. These pathways may be utilised to enhance vaccine efficacy to protect the lung against pneumonia.
Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants
Nirsevimab, a monoclonal antibody targeting RSV, led to decreased hospitalizations for RSV-associated lower respiratory tract infection in infants during their first RSV season, in an open-label, pragmatic trial.