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Implications of respiratory syncytial virus seasonality for the timing of passive immunisation scenarios in Latin America and the Caribbean – a cross-sectional modelling study
Get PDFBackground: The variation in respiratory syncytial virus (RSV) seasonality presents challenges for the timing of RSV prophylaxis. Prevention policies must consider seasonal dynamics to protect infants from severe RSV infections. We evaluated the timing and impact of passive immunisation on birth cohorts in Latin America and the Caribbean, accounting for RSV seasonality, duration of protection and uptake.Methods: We characterised the 2010-2019 RSV seasonality by climate region using a moving averages-based method and surveillance data and identified newborns eligible for passive RSV immunisation under varied assumptions of protection duration and strategies. Lastly, we explored different intervention time windows and estimated RSV-associated acute lower respiratory infections (ALRI) averted among newborns. Findings: In 2010-2019, 28 countries reported 317,951 RSV-positive respiratory samples (12.6% RSV positivity). RSV epidemics followed a south-to-north progression, with onset ranging from March to November in subtropical climates, and year-round epidemics in the tropics.Seasonal immunisation benefited newborns born during January-September in temperate countries, while those born year-round in the tropics benefited from immunisation during at least one epidemic. Year-round vaccination covered newborns for at least one season; long-acting monoclonal antibodies (mAb) administered at five months to infants of immunised mothers extended protection through the remaining season. Year-round campaigns suited tropical climates. At 80% coverage, 61.3% (95% CI 60.7-67) and 55% (95% CI 55.0-56.0) RSV-ALRI cases among 0-<12 months were averted through mAb in exemplar temperate and tropical countries, respectively. In subtropical countries, combined RSV maternal vaccination and long-acting mAb averted 57.3% (95%CI:56.8-57.8) of RSV-ALRI. Efficiency per 100,000 doses administered varied minimally across strategies. Conclusions: RSV climatic variations underscored the importance of surveillance in tailoring the timing and extent of annual campaigns. RSV seasonality informs the selection of interventions. Public health initiatives can enhance prevention for newborns by defining optimal windows for immunising at-risk-infants. <br/
Understanding mechanisms of thrombosis and thrombocytopenia with adenoviral SARS-CoV-2 vaccines: a comprehensive synopsis
Get PDFBackgroundThrombosis with thrombocytopenia syndrome is a rare condition known to occur spontaneously or after heparin use. With the advent of COVID-19 vaccines during the pandemic, thrombosis with thrombocytopenia syndrome cases emerged post administration of adenoviral vaccines, termed vaccine-induced immune thrombosis and thrombocytopenia. In response, the thrombosis with thrombocytopenia syndrome consortium was formed to deepen our understanding of this syndrome post vaccination.MethodsThe consortium employed a comprehensive approach across five work packages. This included designing cohort studies covering the entire English population and analysing local linked regional data sets to detect thrombosis with thrombocytopenia syndrome occurrences in real time. Various patient and healthy control specimens, including those from vaccinated individuals, underwent testing for antiplatelet factor 4 antibodies using three different assays. Patients who developed vaccine-induced immune thrombosis and thrombocytopenia after the AstraZeneca (AZD1222) COVID-19 vaccine underwent whole-genome and ribonucleic acid sequencing to identify genetic susceptibility factors. Multiple studies were conducted to investigate the mechanism of antiplatelet factor 4 antibody formation, including assessments of adenoviral vector structure and binding to platelet factor 4. Detailed studies were also conducted to understand the immune response to vaccines, the role of immune complexes involving platelet factor 4 and their effects on proinflammatory cytokines, neutrophil extracellular traps and platelets in the pathogenesis of the syndrome.ResultsCohort studies revealed a higher risk of arterial and venous thromboses after COVID-19 infection compared to vaccination. Specifically, regarding vaccines, the risk of thrombosis and/or thrombocytopenia was higher after the first dose of the AZD1222 vaccine but not with subsequent doses of. Regional linked data indicated that real-time ascertainment of diseases across multiple acute hospital sites’ secure data environments is not yet feasible at scale. The overall background seroprevalence of antiplatelet factor 4 antibodies was low in healthy individuals, vaccinated individuals and those infected with COVID-19. Whole-genome sequencing did not identify significant variants predisposing to vaccine-induced immune thrombosis and thrombocytopenia, with ongoing work on ribonucleic acid sequencing. An electrostatic interaction between the hexon hypervariable regions of the ChAdOx1 capsid and platelet factor 4 was suggested as a possible mechanism for antiplatelet factor 4 antibody development. Strong immune response drove the formation of neutrophil extracellular traps, significant inflammatory responses and clot formation in distant organs. Platelet activation post immune complex formation against platelet factor 4 was dependent on FcγRIIa but independent of complement, also occurring through binding with c-Mpl. T-cell reactivity against the AZD1222 vaccine indicates potential cross-reactivity with prevalent human adenoviruses.ConclusionsThe consortium’s comprehensive work has uncovered new potential mechanisms of vaccine-induced immune thrombosis and thrombocytopenia and identified novel biomarkers and therapeutic strategies for further development and validation. This is crucial, as the combination of thrombosis and thrombocytopenia, alongside antiplatelet factor 4 antibodies, can occur without exposure to heparin or adenovirus vaccines.Future considerationsRecommendations include the development of a national reference laboratory and registry for diagnosis and further study of thrombosis with thrombocytopenia syndrome; future vaccine development using the adenoviral vector platform to focus on the reduction of the electrostatic interaction between viral hexons and platelet factor 4; international genomics collaboration; and studies focused on understanding the symptoms suffered by patients as well as strategies to ameliorate them.LimitationsDirect identification of vaccine-induced immune thrombosis and thrombocytopenia patients was hindered by poor recording. The rarity of vaccine-induced immune thrombosis and thrombocytopenia limited the number of patients recruited for genomic and mechanistic studies.FundingThis synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme as award number NIHR135073
The Bottle Imp/'O le Fagu Aitu:A Graphic Adaptation Inspired by the Work of Robert Louis Stevenson
No full textA graphic adaptation of Robert Louis Stevenson’s short story, ‘The Bottle Imp’ by Hawaiian artist, Solomon Enos. The adaptation is the outcome of the AHRC funded research project, Remediating Stevenson: Decolonizing Robert Louis Stevenson’s Pacific fiction through graphic adaptation, arts education and community engagement. The book contains a wordless graphic adaptation, a summary of the story in modern English, an illustrated biography of Stevenson and his relationship to the Pacific by Jack Brougham, as well as an outline of, and link to, teaching resources developed by Scotdec for use in Scottish classrooms at Curriculum for Excellence Level 2
Research priorities in vulvodynia:A modified Delphi study
No full textBackground: Vulvodynia is a chronic, unexplained pain in and around the vulva, likely involving an interplay of biological and psychosocial factors. Women with vulvodynia often experience delayed diagnoses, ineffective treatments, and significant quality of life impacts, compounded by social stigma and negative healthcare experiences. Despite its prevalence, our understanding of vulvodynia and its impacts remains limited. Objectives: To establish research priorities that address critical knowledge deficits and improve outcomes for individuals affected by vulvodynia. Design: A mixed-methods participatory study using a modified electronic Delphi (e-Delphi) approach combined with focus groups. Methods: A three-phase modified e-Delphi process was combined with focus groups to gather insights from patients, clinicians, and researchers with expertise in vulvodynia. In Phase 1, participants generated research topics through surveys and focus group discussions. In Phase 2, these topics were rated and ranked by participants to generate a preliminary “top 10” list of priorities. In Phase 3, participants re-rated and re-ranked the preliminary list to achieve consensus on the final research priorities. Results: The top three priorities identified were: (1) Creating a person-centred care pathway and increasing awareness, education, and training of clinicians on vulvodynia, (2) Development of multidisciplinary pain teams, and (3) Creating accessible information for patients on treatment options and self-care advice. Conclusion: This study highlights the importance of integrating the perspectives of those with lived experience, healthcare professionals, and researchers to identify research priorities with the greatest potential for impact. Findings provide a roadmap for future vulvodynia research, support efficient resource allocation, and inform policy development. Furthermore, these results provide a foundation for grassroots initiatives to improve awareness, education, and care for individuals affected by vulvodynia.</p
Sex ratio theory for facultative parthenogens: from fortuitously optimal stick insects to the origin of haplodiploidy in Hymenoptera
No full textSex ratio theory usually assumes obligate sex; rare exceptions with facultative sex typically consider idiosyncratic cases of cyclic parthenogens. Here, we construct a general theoretical framework for facultative parthenogens. We show that facultative parthenogenesis selects for female-biased sex ratios by elevating the class reproductive value of females. The degree of this bias depends on the future rate of parthenogenesis. This complicates calculations for cyclic parthenogens, but in stable environments (with stable rates of parthenogenesis), the optimal sex ratio can result automatically from constraints caused by preexisting sex chromosomes: if sexually produced offspring retain unbiased sex ratios while parthenogenetically produced offspring are female (example: stick insects), optimality is achieved for any rate of parthenogenesis. Conversely, in birds and haplodiploids, parthenogenesis produces males, resulting in suboptimal sex ratios. Nevertheless, male-producing parthenogenesis can invade and reach an equilibrium frequency, if the reproductive value of parthenogenetically produced brood is compromised by less than 50%. We argue that this condition is not met in birds due to inviable WW and homozygous ZZ offspring. For haplodiploids, on the other hand, our work resurrects a somewhat forgotten idea by Bull (1981) that haplodiploidy in Hymenoptera evolved from a diplodiploid ancestor with complementary sex determination
Suction Leap-Hand:Suction cups on a multi-fingered hand enable embodied dexterity and in-hand teleoperation
No full textThis is a technique report to introduce our designed hand with suction cups on its fingertips and palm, Suction Leap Hand (S-Leap Hand). By simply mounting suction cups on a three-fingered dexterous hand, we bring two advantages: much more dexterity for in-hand manipulation and the ability to teleoperate of in-hand manipulation, which are two features that are challenging for existing dexterous hands. We show some demonstrations of in-hand manipulations, e.g., in-hand reorientation, multiple object grasping, and grasping pose changing, that are challenging for current robot hands. Furthermore, we show some tasks that are even challenging for humans, e.g., in-hand peg-in-hole. CAD models and teleoperation codes will be available soon.<br/
Re-evaluating malarial retinopathy to improve its diagnostic accuracy in paediatric cerebral malaria:A retrospective study
No full textBACKGROUND: Previous work has identified that malarial retinopathy has diagnostic value in paediatric cerebral malaria (CM). To improve our understanding of malarial retinopathy as a predictor of cerebral parasite sequestration in paediatric CM we reviewed data from the Blantyre autopsy study, to test the hypothesis that malarial retinopathy is an accurate predictor of cerebral parasite sequestration in an autopsy cohort.METHODS AND FINDINGS: We performed a retrospective analysis of data collected from a consecutive series of patients presenting to the Pediatric Research Ward at Queen Elizabeth Central Hospital in Blantyre, Malawi between 1996 and 2010. We determined the diagnostic accuracy of malarial retinopathy as a predictor of cerebral parasite sequestration in a cohort of children with fatal CM. Of 84 children included in the study, 65 met the World Health Organization clinical diagnostic criteria for CM during life. Eighteen (28%) of 65 did not have evidence of cerebral parasite sequestration at autopsy and 17 had an alternative cause of death. Malarial retinopathy had a sensitivity of 89.4% (95% CI [77.6%, 95.6%]) and specificity of 73.0% (95% CI [57.2%, 84.8%]) to predict cerebral parasite sequestration. In a subset of patients with graded retinal assessments, this was improved to 94.3% (95% CI [81.7%, 98.7%]) and 88.0% (95% CI [70.4%, 96.2%]) by reclassifying patients in whom the only retinal sign was 1-5 haemorrhages in a single eye as retinopathy negative. This study is limited by its retrospective nature and the inherent selection bias associated with autopsy studies.CONCLUSIONS: Malarial retinopathy remains the most specific point-of-care test for CM in endemic areas. Its specificity may be improved, without sacrificing sensitivity, by reclassifying patients in whom the only retinal sign is fewer than 5 haemorrhages in a single eye as malarial retinopathy negative. A management algorithm is proposed for integration of malarial retinopathy into clinical care in both well-resourced and resource-limited environments.</p
Bacterial communities co-develop with respiratory immunity early in life, linking dysbiosis to systemic monocyte signature and wheezing
No full textEarly microbial colonization influences respiratory disease risk, yet mechanisms remain unclear. In a prospective birth cohort of 256 infants, we profiled bacterial, fungal, and viral communities in the upper airway and assessed local immune gene expression longitudinally and systemic gene expression at 1 year. Bacterial populations, not fungal or viral, correlated most strongly with immune development during the first 3 months, coinciding with composition shifts and immune-related gene expression changes, including interferon and adaptive immunity pathways. In contrast, the mycobiome and resident viruses showed no significant coevolution with host immunity. By 1 year, infants who previously wheezed displayed an upper airway microbiota enriched in Haemophilus influenzae and Moraxella, accompanied by a distinct local and systemic immune gene signature featuring elevated classical monocyte-related genes. These findings reveal a specific link between early-life bacterial dysbiosis, monocyte-related immunity, and wheezing onset, suggesting potential targets for early intervention in respiratory disease.</p
Genetic insights into the major histocompatibility complex class I BF2 gene of Korean native chickens in relation to the LEI0258 microsatellite marker and the 90-SNP panel
No full textThe chicken major histocompatibility complex (MHC) represents a “minimal essential MHC” consisting of classical class I (BF) and class II (BL) molecules that present peptides to CD8+ cytotoxic and CD4+ helper T cells, respectively. Class I molecules, primarily encoded by the BF2 gene, are central to immune responses against pathogens. Moreover, these molecules show enormous genetic diversity driven by a molecular arms race with pathogens that determines peptide binding to the polymorphic α1 and α2 domains. Genotyping tools such as the 90-single nucleotide polymorphism (SNP) panel for the MHC-B region (BSNP) and the LEI0258 microsatellite marker have revealed MHC diversity in chickens but do not capture the variation within the α1 and α2 domains. In this study, six populations of Korean native chickens (KNC) were analyzed to assess BF2 gene diversity in individuals homozygous for both the BSNP panel and LEI0258 marker. Two standard BF2 alleles, B06 and B09, were identical while seven additional haplotypes showed high similarity to those found in KNC samples. A total of 30 novel SNPs were identified, with over half located in peptide-binding regions. Most variants overlapped with previously reported data from polymerase chain reaction (PCR) and next-generation sequencing (NGS), leading to the identification of four unique BF2 alleles in KNC. There was no clear relationship among BSNP, the LEI0258 marker, and the BF2 gene, but individuals homozygous for the first two markers also had a homozygous BF2 region. These findings provide insights into MHC diversity and immune potential in KNC populations, supporting conservation and breeding strategies for enhanced disease resistance.Key points• LEI0258 marker and BSNP haplotypes are good indicators of BF2 gene homozygosity.• Unique BF2 alleles from the KNC lines indicate high genetic diversity that can be used for selective breeding and conservation to enhance disease resistance
Clinical and cost-effectiveness of diverse posthospitalisation pathways for COVID-19:a UK evaluation using the PHOSP-COVID cohort
No full textBACKGROUND: Long covid has emerged as a complex health condition for millions of people worldwide following the COVID-19 pandemic. Previously, we have categorised healthcare pathways for patients after discharge from hospital with COVID-19 across 45 UK sites. The aim of this work was to estimate the clinical and cost-effectiveness of these pathways.METHODS: We examined prospectively collected data from 1013 patients at 12 months postdischarge on whether they felt fully recovered (self-report), number of newly diagnosed conditions (NDC), quality of life (EuroQoL-five dimension-five level (EQ-5D-5L) utility score compared with pre-COVID estimate) and healthcare resource costs (healthcare records). An analysis of the cost-effectiveness was performed by combining the healthcare resource cost and 1-year EQ-5D (giving a quality-adjusted life-year (QALY)) using statistical models that accounted for observed confounding.RESULTS: At 1 year, 29% of participants felt fully recovered, and 41% of patients had an NDC. The most comprehensive services, where all patients could potentially access assessment, rehabilitation and mental health services, were more clinically effective when compared with either no service or light touch services (mean (SE) QALY 0.789 (0.012) vs 0.725 (0.026)), with an estimated cost per QALY of £1700 (95% uncertainty interval: dominated to £24 800).CONCLUSION: Our analysis supports the need for proactive, stratified, comprehensive follow-up, particularly assessment and rehabilitation for adults after hospitalisation with COVID-19, showing these services are likely to be both clinically and cost-effective according to commonly accepted thresholds.</p
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