Wellcome Open Research最新文献

Background: We investigated the main drivers for current shortages of licensed antibiotics, existing mitigation strategies undertaken and potential barriers in their implementation through in-depth interviews with experts operating in select regions.

Methods: Purposive sampling was used to identify opinion leaders with expertise in managing antibiotic supply chains, access, and shortages between August 2023 and April 2024. Consented participants were interviewed using a semi-structured interview guide developed using the PESTELI (political, economic, sociological, ecological, technological, legal, industry) framework. Data collection and analysis were iterative and recursive, using constant comparison.

Results: Participants who were interviewed (n=16) had local, national, and global roles in managing and studying access, supply, and demand chain management from Europe, South Africa, India and USA. Political engagement on antibiotic shortages is reported to facilitate effective mitigation strategies, especially in areas where there is strong evidence of government investment. Legal measures have also been used; for example, pharmacists in the UK being given rights to automatically substitute antibiotics on prescriptions and negotiating with pharmaceutical companies for greater transparency on the challenges in manufacturing. Economic incentives are currently missing and are recognised as being a driver for lack of engagement on this topic from pharmaceutical industry. Greater transparency is required from the pharmaceutical companies on the manufacturing chain issues that may lead to shortages. Technologically there is a major gap in systems to forecast and manage antibiotic shortages. Sociological elements include adopting appropriate communication to not cause panic buying and hoarding by organisations when there is an impending shortage. Legislative changes are linked to the political and economic barriers for cohesive systems to manage the antibiotic manufacture and supply chain in relation to shortages.

Conclusion: Currently there are limited interventions to respond to and manage shortages. The antibiotic manufacture and supply chain is complex and under the influence of PESTELI indicators which will need to be understood and mitigated in different contexts and regions.

We present a genome assembly from an individual male Colocasia coryli (Nut-tree Tussock; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence has a total length of 768.61 megabases. Most of the assembly (99.73%) is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled, with a length of 15.31 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces reference genomes for eukaryotic species found in Britain and Ireland.

We present a genome assembly from an individual male Colostygia multistrigaria (Mottled Grey; Arthropoda; Insecta; Lepidoptera; Geometridae). The assembly contains two haplotypes with total lengths of 482.72 megabases and 504.67 megabases. Most of haplotype 1 (99.19%) is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 17.63 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces reference genomes for eukaryotic species found in Britain and Ireland.

We present a genome assembly from an individual male Chrysomela saliceti (leaf beetle; Arthropoda; Insecta; Coleoptera; Chrysomelidae). The assembly contains two haplotypes with total lengths of 738.63 megabases and 703.32 megabases. Most of haplotype 1 (98.68%) is scaffolded into 17 chromosomal pseudomolecules, including the X sex chromosome. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 21.9 kilobases. Gene annotation of this assembly on Ensembl identified 14 722 protein-coding genes. This assembly was generated as part of the Darwin Tree of Life project, which produces reference genomes for eukaryotic species found in Britain and Ireland.

We present a genome assembly from an individual Cepaea hortensis (white-lipped garden snail; Mollusca; Gastropoda; Stylommatophora; Helicidae). The genome sequence has a total length of 3 168.99 megabases. Most of the assembly (97.52%) is scaffolded into 22 chromosomal pseudomolecules. The mitochondrial genome has also been assembled, with a length of 15.08 kilobases. Gene annotation of this assembly on Ensembl identified 17 974 protein-coding genes. This assembly was generated as part of the Darwin Tree of Life project, which produces reference genomes for eukaryotic species found in Britain and Ireland.

Background: Patient and public involvement and engagement (PPIE) in research is a collaboration between researchers, patients, and the public, enhancing research acceptability, relevance, and impact. There is a growing prevalence of PPIE in high-income country research; however, its integration in low- and middle-income countries (LMICs) remains poorly understood. Recognising this gap, the Ziauddin University Clinical Trials Unit in Karachi, Pakistan, launched a dedicated PPIE initiative in 2022. This study evaluates the engagement process and experiences of patient and public members and researchers to identify barriers and facilitators to participation within the PPIE group.

Methods: The evaluation uses an explanatory sequential mixed-method design. First, the Public and Patient Engagement Evaluation Tool (PPEET) questionnaire will be administered online to group members, coordinators, and senior institutional leads. Insights from questionnaires will be further explored during semi-structured interviews, with questions guided by the Patient Engagement in Research (PEIR) framework, supplemented with analysis of project documentation. Study activities will be conducted in both English and Urdu. The study has been co-designed with PPIE members and is co-led with a public partner. Findings will highlight areas for improvement, inform best practices, and guide the development of more effective engagement strategies.

Outcome: Although focused on a single group, this evaluation lays the groundwork for understanding PPIE practices in LMIC contexts. It provides valuable insights into developing equitable partnerships and improving patient-centred research. This study contributes to a growing body of knowledge, offering practical guidance for implementing PPIE in settings with unique socioeconomic challenges and cultural realities. The findings are expected to benefit the local research community and similar initiatives globally, particularly in regions with comparable challenges.

Trypanosoma brucei is an extracellular eukaryotic parasite that causes sleeping sickness in humans and Nagana, Surra and Dourine in livestock, game animals and horses. The parasite displays an extensive immune evasion mechanism, utilising the expression and ability to switch antigenically distinct variant surface glycoprotein (VSG) coats. VSG encoding genes account for ~10% of the T. brucei genome, and mosaic VSGs, assembled from distinct incomplete VSG gene copies, can be produced from this VSG library, generating an almost infinite VSG repertoire, which enables chronic infections. Each parasite expresses just one VSG at a time, but within a host, many VSGs can be expressed simultaneously. Understanding patterns of VSG expression is therefore central to studying parasite dynamics, tissue tropism, and infection persistence. VSGSeq is an amplicon sequencing approach that enables surveillance of the population-wide diversity and abundance of expressed VSGs. We present vsgseq2, an updated and fully reproducible workflow for analysing VSGSeq data. Implemented in Nextflow, vsgseq2 integrates modern tools for transcript assembly and quantification, improves computational efficiency. Benchmarking against defined T. brucei VSG expression datasets demonstrated that vsgseq2 accurately reconstructs population-wide VSG repertoires and better recapitulates VSG expression proportions. Analyses of in vivo infection data further confirmed that vsgseq2 enhances reproducibility and improves data utilisation, and improves computational efficiency. vsgseq2 enables researchers to efficiently and reproducibly analyse complex VSG expression data and the mechanisms driving immune evasion in T. brucei.

Background: Learning platforms can strengthen primary healthcare (PHC) by integrating community knowledge with system decision-making, but evidence on how they work in low-resource settings is limited. This study presents a realist evaluation of the Verbal Autopsy with Participatory Action Research (VAPAR) learning platform in rural Mpumalanga, South Africa (2015-25). VAPAR aimed to embed participatory evidence generation and shared learning within routine district processes to support more equitable, community-linked PHC.

Methods: A realist design was used to synthesise data from five action-learning cycles (2017-23), a preceding pilot (2015-16), and an engagement and uptake phase (2023-25). Data included cycle reports, participatory outputs, verbal autopsy (VA) analyses, 22 endline interviews, policy, strategy and planning documents. Using a co-developed theory of change, qualitative data were coded to examine context-mechanism-outcome patterns. Mechanisms were identified and refined through cross-cycle comparison, triangulation, and stakeholder validation.

Results: VAPAR was contextually responsive, adapting to shocks such as COVID-19 and progressively embedding within the district health system. Through regular dialogue, the platform activated generative mechanisms of trust-building, role clarity and recognition, collective sense-making, and strengthened agency, particularly among Community Health Workers (CHWs), whose skills, confidence and legitimacy expanded. These mechanisms operated within an enabling structural context shaped by PHC reforms that strengthened the District Health System and Ward-Based Primary Health Care Outreach Teams, alongside trade-union action for CHW absorption into public service. Institutionalisation followed through Mpumalanga's revitalised Health Promotion Programme, with adaptation to additional provinces and for outbreak response and emergency obstetric care. Outcomes were interpreted through context-mechanism-outcome patterns, illustrating how participatory learning becomes embedded in decentralised health systems.

Conclusions: Over a decade, VAPAR demonstrated how structured, participatory learning can reshape relationships, strengthen community-linked PHC, and support institutionalisation of routine, evidence-informed practice in decentralised health systems. The findings offer transferable lessons for sustaining learning platforms in resource-constrained settings.

Introduction: Data science health research (DSHR) presents new ethical challenges to the traditional model of human subject research, particularly by enabling data processing without the consent of data subjects. Although the current research governance framework makes informed consent a cornerstone of ethical research practices, obtaining individual consent can often be impractical in DSHR. This paper explores the alignment of DSHR with African customary governance and communal lifestyles as a framework for ethical research oversight.

Methodology: This paper adopts a case study methodology, using a comparative analysis of decolonisation and self-regulation in health research across five African countries-Nigeria, Kenya, Ghana, Uganda, and South Africa. The study combines doctrinal analysis of legal and policy frameworks with reviews of peer-reviewed literature, case law, and diverse online resources such as PubMed, Google Scholar, HeinOnline, and government websites.

Results: Data science health research challenges traditional biomedical ethics by enabling data processing without consent, thereby questioning the longstanding principle that informed consent is a prerequisite for ethical research. However, this principle has been widely contested as a universal standard, particularly in African contexts where decision-making is often communal rather than individualistic. The case studies illustrate that while informed consent remains a normative requirement, largely to satisfy the expectations of funding bodies, communal approval is paramount. Furthermore, religious and cultural traditions often accommodate forms of paternalistic consent, reinforcing collective decision-making structures.

Conclusion: Given that African societies emphasise communal governance, the ethical challenges posed by DSHR, particularly regarding consent, may be less pronounced in Africa. However, decolonisation and self-regulation are not merely theoretical constructs, but a practical and necessary process that requires deliberate action. Unless African leaders take decisive steps to restructure governance, prioritise self-reliance, and invest in homegrown research and development, the discourse on decolonising DSHR in Africa will remain purely theoretical, lacking the practical implementation needed for real change.

Background: Acute respiratory illnesses (ARI) are a major cause of morbidity and mortality globally. With (re)emergence of novel viruses and increased access to childhood bacterial vaccines, viruses have assumed greater importance in the aetiology of ARI. There are now promising candidate vaccines against some of the most common endemic respiratory viruses. Optimal delivery strategies for these vaccines, and the need for interventions against other respiratory viruses, requires geographically diverse data capturing temporal variations in virus circulation.

Methods: We leveraged three health facility-based respiratory illness surveillance platforms operating in 11 sites across Kenya. Nasopharyngeal (NP) and/or oropharyngeal (OP) specimens, patient demographic, and clinical characteristics were collected in 2014 from individuals of various ages presenting with respiratory symptoms at the surveillance facilities. Real time multiplex polymerase chain reaction was used to detect rhinoviruses, respiratory syncytial virus (RSV), influenza virus, human coronaviruses (hCoV), and adenoviruses.

Results: From 11 sites, 5451 NP/OP specimens were collected and tested from patients. Of these, 40.2% were positive for at least one of the targeted respiratory viruses. The most frequently detected were rhinoviruses (17.0%) and RSV A/B (10.5%), followed by influenza A (6.2%), adenovirus (6.0%) and hCoV (4.2%). RSV was most prevalent among infants aged <12 months old (18.9%), adenovirus among children aged 12-23 months old (11.0%), influenza A among children aged 24-59 months (9.3%), and rhinovirus across all age groups (range, 12.7-19.0%). RSV had a higher virus positivity in the inpatient setting (12.5%) compared to outpatient setting (4.8%). The overall percent virus positivity varied by surveillance site, health facility type and case definition used in surveillance.

Conclusions: We identify rhinoviruses, RSV, and influenza A as the most prevalent respiratory viruses. Higher RSV positivity in inpatients, and in infants, strengthens the case for RSV vaccination. To inform the design and delivery of public health interventions, long-term surveillance is required to establish regional heterogeneities in respiratory virus circulation and seasonality.