NIHRDataInsights/HRCSData huggingface dataset:
Title: Foresight Study on European Stakeholder Appraisal of Diagnostics to Manage Anti-Microbial Resistance
Funder: Economic and Social Research Council

Abstract: We will facilitate stakeholder appraisal of pathways to development and use of diagnostics to address the AMR challenge. We address four questions: 1.What are the stakeholders' priorities for the types of diagnostics to manage AMR? 2.What informs stakeholder preferences? 3.What scenarios can best deliver the preferred diagnostics? 4.Where is there agreement or obstacle to progress in advancing particular scenarios? The project has four phases. Phases A & B involve a pan-European survey developed to ascertain the technical (and other) characteristics of diagnostics that stakeholders in different nations would most support and the associated challenges they identify - delivered as an online stated preference survey. We expect to detect statistically significant inter-group and international differences in priorities. Survey results will inform the design of scenarios for phase C, which centres on Multicriteria Mapping (MCM) interviews with representatives from stakeholder groups around innovation pathways for diagnostics. MCM allows stakeholders to appraise scenarios (e.g. funding models/ incentive schemes) using any criteria they deem appropriate (i.e. not limited by the starting assumptions of the investigators, and open to creation of scenarios devised by participants). MCM allows comparisons across scenarios and across stakeholder groups in numerous ways, without reducing complex data to linear single ordering of preferences. Instead MCM allows differences between priorities and problems that stakeholders raise to be revealed, displayed, and discussed. Results may demonstrate incompatibility with stakeholders (and elimination) of some scenarios but will also show obstacles to be overcome to allow other scenarios to be developed and may reveal areas of consensus. Phase D involves production of up to four academic articles for submission, the launch of a policy briefing and extensive meetings in Europe, the US and China to encourage use of the research findings.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);8.2 HEALTH AND WELFARE ECONOMICS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: INFECTION
Title: Studies towards infectious disease elimination on the Bijagos Archipelago of Guinea Bissau
Funder: Economic and Social Research Council

Abstract: We have been studying the epidemiology of trachoma, a neglected tropical disease (NTD) caused by Chlamydia trachomatis infection, which remains the leading infectious cause of blindness worldwide, in the Bijagos Islands of Guinea Bissau since 2010. We used whole genome sequencing and geospatial analysis to map the transmission of ocular C. trachomatis in these communities, and have shown that elimination of blinding trachoma should be possible through mass treatment with azithromycin, as recommended by WHO, although it is likely that behavioural interventions and improved sanitation will be needed to ensure that elimination is sustained. These remote islands are an ideal setting in which to evaluate new tools and strategies for the elimination of infectious diseases through cluster-randomised trials, since there is little migration between the 20 inhabited islands, and each can be treated as an independent cluster. Over the next two years we propose to use a multi-disciplinary approach to map the geographical distribution, routes of transmission and socio-behavioural determinants of malaria, trachoma and other NTDs including yaws, lymphatic filariasis, schistosomiasis, scabies and soil transmitted helminths on the islands, with the aim of developing new strategies for disease elimination that can be evaluated through cluster-randomised trials. We will establish a laboratory and insectary on the islands and train staff in diagnostic parasitology, mosquito collection and identification, and the collection of qualitative and quantitative data in the field. We will conduct population-based surveys to map the epidemiology of these diseases, using two-stage cluster sampling, and collect information on hygiene related behaviours, local beliefs concerning disease causation and attitudes towards potential interventions through direct observation, semi-structured interviews, focus group discussions and interviews with key informants.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Optimal control strategies for rodent-borne zoonoses in Brazilian slum settlements
Funder: Economic and Social Research Council

Abstract: It is widely accepted that controlling the spread of infection from rodent reservoirs to humans in urban slums, particularly in poor countries, is a challenge that must be addressed. We focus on leptospirosis in the urban slums of the city of Salvador, Brazil, which is important in its own right, but our project is directly relevant to other zoonoses and to the health of these communities more generally. Our overarching aim is to develop the means of enabling agencies working locally to minimise the threat that these reservoirs pose, using methodologies that can be applied effectively, cheaply, and without the need for a sophisticated infrastructure. We are in an arguably unique position to do this with an international multi-disciplinary team from medics to social scientists, and with strong links to local public health agencies. The overall structure of our study will be a cross-sectional comparison of three sanitation-control measures currently being employed. These three have been operational for long enough, and provide us with sufficient sites (three of each) to support statistically valid comparisons. At each site, we will collect data on (i) rat abundance; (ii) the prevalence in rats of leptospires and other key pathogens (iii) concentrations of pathogenic leptospires in the environment; (iv) seroprevalence in humans for leptospires and these other key pathogens; (v) severe cases of leptospirosis reported in humans over the last 20 years; and (vi) attitudes of local residents to methods of sanitation control, especially in relation to effects on disease risk. These data will be combined, first, simply to compare the efficacies of current practices. But we will additionally use optimal control modelling, combined with the data on human attitudes, to explore the cost-effectivenesses of the practices, and whether new or combinations of strategies could further improve cost-effectiveness.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Towards a global research network for the molecular pathological stratification of leishmaniasis.
Funder: Economic and Social Research Council

Abstract: The leishmaniasis are complex diseases, showing great diversity in clinical presentation and in response to drug treatment, across individual patients as well as across geographic boundaries. The adoption of stratified approaches to treatment with existing as well as new drugs and /or drug combination therapies could have a considerable impact on the direct and indirect costs associated with treatment and significantly improve patient well-being. In this Foundation Award, we aim to set the scene for a change in the way we conduct clinical research in leishmaniasis. Using Nanostring nCounter analysis of formalin fixed paraffin embedded (FFPE) sections, we will maximise the data obtained from diagnostic tissue samples and use this information to start to develop multiplex point of care assays that can be used in a resource poor setting. We will assess the added value to research, clinical decision making and education and training that can be achieved thorough the development of an internet-based telepathology network, initially linking "scanning" hubs in Brazil and York with remote viewing stations in Sri Lanka and India. We will use a series of scoping workshops to i) inform the development of a new clinical grading tool for tegumentary leishmaniasis (based on advances being made for other dermatological diseases) and ii) to understand the health economic implications of adopting this approach and to seek evidence for added value for the research community and for health systems in LMICs. Each of the specific project aims has been structured to provide the necessary preliminary data and, where appropriate, explore the industrial partnerships necessary to underpin future funding applications and / or commercial sector engagement in 12-18mth time. At the completion of the Foundation Award, these studies will have also delivered new knowledge of importance in its own right and suitable for publication.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: Cultural, social and economic influences on ongoing Schistosoma mansoni transmission, despite a decade of mass treatment, and the potential for change
Funder: Economic and Social Research Council

Abstract: Over 240 million people are infected with schistosomiasis, which causes severe morbidity and reduces physical and cognitive development. Despite over a decade of mass drug administration (MDA) to reduce morbidity and aid disease elimination, hotspots of Schistosoma mansoni infections remain. MDA alone will not reduce transmission; additional interventions are required. S. mansoni transmission is linked to poor Water, Sanitation and Hygiene (WASH) conditions with parasite eggs excreted in human stool. This project aims to better understand how people living in endemic communities manage their risk of S. mansoni and how they might change their behaviour if additional resources were provided. The work is divided into two work packages. WP1 will use rapid ethnographic appraisal to understand how people talk about S. mansoni and respond to on-going interventions such as MDA and WASH resources, how people's behaviour contributes to transmission and re-infection, and the social, economic and cultural barriers that prevent change. WP1 will provide data to WP2, which will estimate an averting behaviour model for risk reduction using count-data modelling. Our model will identify the associations between (i) household and individual characteristics (ii) attitudes to and knowledge of risks and (iii) the availability of local WASH resources with the extent to which measures to reduce their own and others' risks are taken. Next, a stated preference choice experiment will estimate the probability of take up and use of new WASH resources which could be provided (e.g. pit latrines, wash stations), as a function of both the characteristics of the intervention (e.g. cost, maintenance, location) and the characteristics of respondents. Insights gained from WP1 and WP2 together will provide new, integrated, understanding of best-bet strategies for interventions to reduce the incidence and persistence of this debilitating disease, whilst building social science capacity in Uganda.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: INFECTION
Title: GCRF Partnership for Increasing the Impact of Vector Control (PIIVeC)
Funder: Economic and Social Research Council

Abstract: Vector-borne diseases are pervasive, causing massive morbidity and mortality and severely retarding economic development across the developing world. Many of our current tools are inadequate in twenty first century urban environments or failing due to insecticide resistance, and the evidence base for newer interventions remains weak. Selecting the most cost effective, affordable and acceptable tools to reduce the burden of vector borne disease requires an integrated approach involving vector biologists, economists and anthropologists, working in partnership with national ministries of health, planning and finance. In reality, most disease endemic countries lack the capacity to develop evidence based strategies to control these diseases. There is a particularly acute shortage of vector biologists but also an urgent need to attract leading scientists from other disciplines to tackle this major public health crisis. This proposal will establish a Partnership to Increase the Impact of Vector Control. We will bring together leading research institutes and national disease control programmes from three African countries with exceptionally high burdens of vector borne disease, Burkina Faso, Cameroon and Malawi, to develop evidence based solutions for integrated vector control. Supported by long term mentorship from LSTM and rigorous evaluation of the capacity needs in-country, the Partnership will generate new knowledge and tools, and strengthen national decision-making leading to reduced disease burden and increased resilience for responding to outbreaks.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Novel antimicrobial surfaces to combat AMR infections in medical implants and devices
Funder: Engineering and Physical Sciences Research Council

Abstract: Medical implants and devices constitute an indispensable and vital component of modern healthcare, resulting in greater survival rates, particularly amongst critically ill patients. However, despite tremendous improvements in surgical procedures, biomaterial-associated bacterial infections remain the dominant cause for prosthetic device or implant failures, resulting in significant patient trauma and a huge healthcare burden on the NHS. Current solutions are largely based upon chemical means (e.g. antibiotics or antimicrobial agents such as silver), which have many shortcomings and limitations. There are also issues associated with the growing problem of antimicrobial resistant (AMR) bacteria. Thus, a completely new way of killing AMR bacteria is urgently needed. In this innovative project we will explore a unique physical means to combat biomaterial-associated bacterial infections, utilising novel surfaces that kill bacteria with nanospikes, that resemble the nanotextured surfaces found on cicada wings in nature and have already been shown to be effective at killing certain bacteria by us. We aim to develop a range of antimicrobial surfaces with nanospikes that exhibit bactericidal properties against a wide variety of infection-associated bacteria. We will also investigate the synergistic effect of enzyme functionalised nanospikes to target peptidoglycan layer within the bacterial cell walls in order to develop novel surfaces with maximum bactericidal properties against AMR bacteria. Taken together, the knowledge generated in this project will be used for the rational design and fabrication of future medical implants and devices to combat AMR infections. This will contribute to the priority areas of national health and the economy, benefiting both patients and the NHS.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: New cell surface markers of bacterial infection
Funder: Health and Care Research Wales (Welsh Government)

Abstract: The “X-ray vision” of the immune systems’ T-cells allows them to see inside other body cells to determine if they contain internal germs. Recognition of an infected cell by T-cells triggers them to destroy the cell and the pathogens within it. Conventional T-cells recognise small building blocks of germ molecular machinery called peptides. These peptides are presented at the surface of the infected cell cradled within molecules called HLA. Over 7000 different HLA molecules have been described to date. As each individual expresses up to 12 different HLA molecules the number of possible combinations is enormous meaning that each individual is almost unique. HLA differences are the major cause of transplant rejection and the difficulty in finding an exact donor match for transplantation serves as a good demonstration of the extent of HLA diversity. HLA diversity also means that different individuals in the population fight invading pathogens through different HLA. Discoveries over the last decade have highlighted that there are other populations of T-cells that recognise bacteria without the involvement of HLA. Some of these T-cells recognise the metabolic pathways that manufacture vitamin molecules while others see bacterial lipids that differ from our own. Interest in these types of unconventional T-cells has exploded since 2012 and they are currently a very hot topic. One of the reasons for this interest is that, unlike ‘HLA-restricted’ T-cells, these unconventional Tcells recognise bacteria through molecules that every single individual in the population shares. This ubiquitous recognition mechanism allows scope for novel pan-population vaccines and anti-microbial herapeutics. We have good evidence that there are yet to be discovered human anti-bacterial unconventional T-cells. We aim to discover what these T-cells recognise in order to harness new ubiquitous biomarkers of bacterial infection to design new therapies.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFECTION
Title: Phase I Study of a MVA based vaccine for Crimean Congo Heamoraghic fever
Funder: Innovate UK

Abstract: Crimean-Congo haemorrhagic fever virus (CCHFV) is a deadly human pathogen and is of the utmost seriousness of being both fast acting and highly lethal. The virus has repeatedly caused sporadic outbreaks with a fatality rate of up to 80, Asia and Eastern Europe. Ticks that are able to transmit this deadly disease are encroaching into northern Europe infecting grazing livestock which is the CCHFV reservoir and an important part of the tick life cycle. Unfortunately there are no available vaccines or therapeutics to this disease. Public Health England scientists have extensive experience of working with this pathogen and developed an experimental CCHF vaccine called MVA-GP. This was produced by engineering a safe vaccine virus (MVA) to produce a key component of the CCHFV. In 2013, PHE published the results of successful trials that showed their experimental vaccine to be 100% effective at protecting animals against challenge with CCHFV. PHE has received funding from the UK Govt to develop the vaccine for animal use to enable widespread protection of farm animals which is a major source of infection to humans. PHE are now applying for funding to prepare clinical grade MVA-GP vaccine so they can perform a small clinical study to demonstrate the vaccine is safe and has the potential of protecting humans against this deadly disease.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Z-RNA and D-DNA: Novel Inducers of Antiviral Immunity
Funder: Lister Institute of Preventive Medicine

Abstract: Virus-derived nucleic acids are powerful triggers for innate immunity. Dr Jan Rehwinkel’s laboratory studies nucleic acid sensors that survey the cytoplasm of cells for viral or unusual DNA and RNA molecules. His interest is in understanding the molecular mechanisms that control activation of these receptors. The group has been focusing on RIG-I-like receptors that sense RNA and on the DNA sensor cGAS. The Lister Prize will support a postdoctoral fellow to test if nucleic acids in the unusual Z-conformation trigger innate immune responses.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: A phase III randomised controlled trial of oral fluconazole plus flucytosine versus amphotericin B-based therapy for o
Funder: Medical Research Council

Abstract: Cryptococcal meningitis is one of the commonest causes of death in cohorts of HIV-infected patients, and of early mortality in antiretroviral (ART) programmes in Africa, being associated with up to 500,000 deaths per year in Africa alone. The high case fatality rate of cryptococcal meningitis is driven in substantial part by the lack of effective antifungal regimens for resource-constrained settings. In many centres the standard initial treatment of 2 weeks intravenous amphotericin B (AmB) is not available or not safely sustainable due to the drug and administration costs, the close monitoring required, and common dose-related side effects. Fluconazole, the commonly used but slowly-acting alternative, widely available through a donation programme, when used alone, is associated with a 10-week mortality of 50-60%. Therefore, based on a series of phase II studies by the study team, 2 novel regimens, (1) Short, 1-week AmB-based induction, and (2) Combination oral therapy with high dose fluconazole plus flucytosine, that are associated with a rate of clearance of infection similar to that seen with 2 weeks AmB, will be compared with the internationally-accepted standard of 2 weeks AmB, in a randomised non-inferiority trial with 2-week mortality as primary endpoint. After 2 weeks, all patients will receive fluconazole consolidation and maintenance therapy, will be commenced on ART at 3-4 weeks, in line with current guidelines, and followed to 10 weeks. 570 patients (190 per arm) will be studied in order to achieve 85% power, using a non-inferiority design with 10% non-inferiority margin, and assuming 85% 2- week survival in the 2-week AmB arm. The project has been developed with collaborators from 3 African sites (Blantyre and Lilongwe, Malawi, and Lusaka, Zambia) with a high, ongoing burden of cryptococcal disease where alternative, sustainable regimens are urgently needed. Each site has laboratory infrastructure in place and experience of conducting trials to GCP standard. Both test regimens have been shown to be much more rapidly active than fluconazole monotherapy, and would be better tolerated and much more easily implemented in resource-limited settings than 2 weeks AmB. Alternatively, if 2 weeks AmB proved superior, then the resources required for its wider implementation could be justified. A cost effectiveness substudy will be developed to inform policy-making decisions.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION