NIHRDataInsights/HRCSData huggingface dataset:
Title: Making and breaking the cell walls of fungal pathogens.
Funder: Wellcome Trust

Abstract: The cell wall of fungal pathogens determines their pathobiology and immunological signature. It is the ideal target for chemotherapies and immunotherapies because all the major cell wall components are essential and fungal-specific. My vision is to innovate and inform therapeutic strategies through an understanding of how the cell wall is assembled and recognised by the immune system. My group are world leaders in the analysis of the major human pathogen Candida albicans, and have made fundam ental advances in cell wall biology. These foundations enable two major new research questions to be addressed, each with translatable outcomes. (i) What are the key assembly processes and functions of the extended gene families that articulate cell wall assembly? To answer this, I will exploit recent advances in C. albicans genetics to pioneer forward genetic methods using recently discovered haploid strains. Novel screens, phenotyping methods and in vitro synthetic biology approaches w ill be deployed to dissect the functions of key families of cell wall genes. (ii) What is the fine chemical structure of cell wall molecules that stimulate, attenuate and imprint the innate and adaptive responses of the immune system? I will use novel, bespoke reagents and combinations of host and pathogen functional analysis tools to study the key immunologically relevant cell wall glycoconjugates. These complementary research questions will result in major advances in our understanding of therapeutically tractable targets of the cell wall, and will inform the design of new generations of therapeutics and diagnostics.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Development of a novel multi-valent, targeted treatment for serious Escherichia coli and Klebsiella pneumoniae infections
Funder: Wellcome Trust

Abstract: Phico Therapeutics Ltd has developed a novel antibacterial platform technology, SASPject, which utilises an antibacterial protein, SASP, which disables all bacteria by inactivating their DNA; without active DNA, bacteria cannot survive or multiply. The SASPject technology couples SASP with nano-delivery vehicles (NDVs). NDVs are made from bacterial viruses (viruses that attack only bacteria), and Phico uses NDVs to selectively deliver SASP to those bacteria which are causing an infection. The unique way in which SASP works, by inactivating bacterial DNA even if it mutates, means that resistance is very unlikely to develop: any potential resistance that the bacteria could develop to the NDV’s themselves is addressed during development. SASPject can potentially be used against any harmful bacteria but being able to target it to selected pathogens avoids damaging the normal human flora. Uniquely, SASP could help to prevent the further spread of existing antibiotic resistance. In this project, led by Dr Heather Fairhead at Phico Therapeutics plans to utilise and extend the company’s knowledge, experience and innovative techniques to produce a SASPject product that can be used intravenously to treat serious infections due to the Gram negative bacteria, E. coli and K. pneumoniae, including those which are multi-drug resistant.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Supporting Research in the Ebola Epidemic Region
Funder: Wellcome Trust

Abstract: This proposal is to fund Professor James Grover Whitworth to lead a small team, based in the UK and in Sierra Leone, to work in the short term to oversee, guide, coordinate and stimulate research in the epidemic region in West Africa. Following the initial period the team will ensure that research can continue along with surveillance as the health systems are rebuilt in the region. In the longer term the team will promote field epidemiology and epidemic response expertise within the UK. To support this work the UK institutions will supply, staff and support an office in the UK and this funding will support the cost of an office in Freetown, Sierra Leone. This funding will support Professor Whitworth"s personal compensation and pension. A small team for Sierra Leone will be recruited as soon as possible with the aim of rotating within the epidemic zone to conduct the shorter-term activities. This funding will support two research officers and one administration officer, to work in Sierra Leone. The funds may also be used for international and local travel. The UK host universities will support an administrative officer to work in the UK office.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: INFECTION
Title: A Virtual Screen to Identify of Hit stage Inhibitors of all four serotypes of Dengue Polymerase
Funder: Wellcome Trust

Abstract: Dengue virus is a mosquito-borne infection that causes a severe flu-like illness and, in a subset of cases, the potentially lethal complications of Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). The World Health Organization estimates 50 million cases of Dengue infection annually worldwide. This project is a unique structure-based approach to develop novel Dengue inhibitors that target a key stage in the virus lifecycle, the prevention of the viral replication and are active against all four serotypes.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Development of small molecule inhibitors of Ebola virus genome replication
Funder: Wellcome Trust

Abstract: Development of small molecule inhibitors of Ebola virus genome replicationThis Pathfinder project will address infection with Ebola virus (EBOV), which has a human mortality rate of over 50%. EBOV is a member of the Filoviridae family (genus Ebolavirus), a negative strand RNA virus that is highly transmissible and causes severe haemorrhagic fever. The recent outbreak of EBOV in West Africa has highlighted the lack of effective therapeutic options for the treatment of this infection. Efficacious small molecule inhibitors of the virus are therefore needed for the rapid treatment of EBOV infected individuals, but their development has been hampered by the requirement to propagate EBOV under Biological Safety Level 4 (BSL4) containment.The project team, led by Professor Mark Harris at University of Leeds, propose to use a combination of in silico drug design and a mini-genome system, which accurately and faithfully recapitulates the essential processes of EBOV gene transcription and genome replication under BSL2 conditions. The team will design small molecule inhibitors based on known high-resolution structures of EBOV proteins involved in these processes, in particular focussing on the essential nucleocapsid protein. This approach builds on existing strengths at the University of Leeds, combining an innovative approach to in silico drug design with extensive experience in both virology and structural biology. The project aims to deliver drug-like lead compounds that can be further developed into therapeutic agents.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: An intervention to reduce the use of antimicrobials in chicken production in Vietnam.
Funder: Wellcome Trust

Abstract: The proposed research will investigate the reduction of antimicrobial use (AMU) levels in chicken production in the Mekong Delta (Vietnam) by providing farmers with a locally-adapted veterinary support system. A randomised before and after controlled trial will be carried out on 120 randomly selected chicken farms. Following, a 12-month (observational) baseline phase, there will be a 18-month intervention phase, with random allocation of farms to one of three arms: (1) Free provision of Farmer T raining and a Farm Health Plan (FTHP) delivered through veterinarians; (2) Replacement of medicated with non-medicated feed, in addition to free FTHP; and (3) No intervention (control). Farms will be longitudinally visited to collect data on AMU (measured in grams of active principle of each type of antimicrobial), health and productivity. The design will capture (1) reductions in AMU (2) the impact of any reductions of the proposed intervention on AMR in commensal enteric bacteria in a random s ubset of farms (15 per arm); and (3) economic trade-offs between the costs of the intervention and gains as a result of savings in antimicrobial usage, improved animal health and productivity, and reductions in AMR in animals and the environment.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Using parasite population genomics to improve understanding of malaria epidemiology
Funder: Wellcome Trust

Abstract: This collaborative project will use genomic approaches to characterise demographic flux and evolutionary trends in the malaria parasite population. Using novel methods for parasite genome sequencing that are suitable for large-scale field applications, we will perform longitudinal studies of parasite population genomics at multiple locations with different transmission intensities in Africa and Southeast Asia, and we will examine the clinical and epidemiological correlates of population genomic variables under a range of ecological settings. We will develop statistical and computational approaches to use longitudinally sampled genome sequencing data to construct spatial maps of parasite demography and examine how this changes over time. We will promote collaboration between experts on population genomics, geospatial mapping and mathematical modelling to use these data to inform and improve epidemiological models of malaria transmission. Our overarching goal is to establish the practical and analytical foundations to use parasite genome sequencing to investigate the causes of epidemiological events such as resurgence and emerging drug resistance, and thus to assist in planning effective interventions.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);2.4 SURVEILLANCE AND DISTRIBUTION;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Health and economic benefits of water-sensitive revitalisation in informal urban settlements
Funder: Wellcome Trust

Abstract: Urbanisation is a major demographic trend globally. Informal settlements account for much urban growth, exacerbating the inextricably linked challenges of sanitation, water provision, and public health. The conventional "big pipes" solution to these challenges has changed little in 150 years, comes at major financial, environmental, and social costs, and frequently overlooks informal settlements. We have pioneered an alternative, water-sensitive approach that integrates sustainable design with the management of the water-cycle, benefiting human health and urban ecosystems. This decentralised, climate-change sensitive approach provides financial flexibility for multistage developments and adaptability to future technologies. It promises a solution to the water services challenges of informal settlements, yet has only been demonstrated in developed world settings. We will examine whether the water-sensitive approach can be applied to revitalise developing-world informal settlements to improve environmental and public health outcomes. Our evidence-based assessment of its efficacy across 24 settlements, poorly served by water infrastructure in Makassar and Suva, will deliver the first public health and environmental data on the benefits and risks of water-sensitive approaches. Our scientific, economic and implementation findings will provide the basis for profound changes to infrastructure policies, investments, loan strategies, and their sustainability across the Asia-Pacific and the developing world.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Cohort of pregnant women with Zika infection and Congenital Zika Syndrome (CZS)
Funder: Wellcome Trust

Abstract: The overall research aim is a full understanding of the epidemiology of the Congenital Zika Syndrome. The objectives are: 1. Determine the proportion of pregnant women presenting with rash (and clinical features compatible with Zika) which has laboratory confirmation of ZIKV infection. 2. Determine the proportion of women with ZIKV viraemia during pregnancy that has an adverse birth outcome (miscarriages, stillbirths) and congenital abnormalities. Also in women with negative ZIKV PCR and IgM but rash compatible with ZIKV. Overall and by gestational age. 3. Describe the range of clinical features of the CZS by describing the whole range of abnormalities in neonates born to women with Zika during pregnancy and how the features vary according to gestational age at infection; both present at birth and diagnosed up to age 6 months. 4. Build a bio-repository of blood samples and genetic material from pregnant women infected with ZIKV and their neonates, linked to the epidemiological data to be used for future research as well as a gold standard to validate new diagnostic tests. 5. Establish a cohort of neonates born to women with Zika during pregnancy for further follow-up.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: INFECTION
Title: STRONGER-SAFE: Understanding transmission and optimising interventions for an enhanced S.A.F.E. strategy for trachoma elimination
Funder: Wellcome Trust

Abstract: Trachoma is the leading infectious cause of blindness worldwide. It is intrinsically linked to poverty in both cause and effect. Preventing blindness from trachoma has broad and profound impact on health and well-being. It is caused by repeated infection with Chlamydia trachomatis (Ct). The WHO-endorsed SAFE-Strategy aims to control infection through annual, single-dose, community-wide azithromycin treatment coupled with Water/Sanitation/Hygiene (WASH) and fly-control measures to suppress transmission. However, particularly in hyperendemic regions, the current approach is not having the anticipated impact. There are two critical issues. Firstly, current azithromycin schedules appear insufficient. Secondly, transmission routes are poorly defined and the very limited evidence-base makes it hard to focus WASH interventions and guide programmatic decisions. We propose the following: 1) Conduct intensive observation of human behaviour and hygiene practice, and fly behaviour, combined with Ct infection mapping, to identify major routes of transmission. 2) Develop and test contextually appropriate, practical, targeted WASH and fly-control approaches to interrupt Ct transmission. 3) Our modelling work indicates double-dose azithromycin two weeks apart is much more effective in controlling Ct. In a cluster-randomised trials we will test whether intensified double-dose treatment coupled with targeted transmission-interrupting strategies cancontrol trachoma more effectively.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Hypersialylated Fcs for the treatment of antibody-mediated CNS demyelination and microglial activation
Funder: Wellcome Trust

Abstract: In neurology, intravenous immunoglobulin (IVIg) serves as a mainstay therapy in immunemediated neuropathies, including chronic inflammatory polyneuropathy (ClOP) and GuillainBarre syndrome. The worldwide consumption of IVIg has increased over 300 fold since 1980 and currently -100 tons are consumed per annum. Supplies of IVIg within the NHS and globally are critically limited, meaning that patients with an urgent need for the drug are routinely deprived of it. There are significant clinical limitations resulting from its dependence on human donors for manufacture, and from the fact that <5% of injected IVIg (correctly glycosylated Fe) is therapeutically active leading to a requirement for high doses (2g/kg) when used to treat inflammatory conditions, including ClOP. Consequently, IVIg is expensive and adverse events due to excessive protein loading are not uncommon. These challenges associated with manufacturing and application of IVIg represent an incentive to develop molecules with improved efficacy. Professor Richard Pleass at the Liverpool School of Tropical Medicine has developed a means to manufacture recombinant hypersialylated Fcs that bind critical receptors implicated in controlling CIDP. Together with Professor Norbert Goebels and colleagues at the University of Dusseldorf, they will test if lead molecules protect in pre-clinical models of CIDP, a prerequisite for on-going commercialization and translation to human studies.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Translation of virus like particle foot-and-mouth disease vaccine research to commercial development
Funder: Wellcome Trust

Abstract: Foot-and-mouth disease (FMD) is a highly contagious, acute viral disease of cloven-hoofed, domesticated and wild animals. There are many variants of FMD which cause a global economic impact, estimated at between US$ 6.5 and 21 billion per year. Current vaccines are made of inactivated viruses which are fragile structures that can limit production and result in poor immunity after vaccination. Large quantities of live FMD virus are grown during production in very expensive high containment facilities. Consequently, there is a huge undersupply of vaccine globally, especially in Africa. We have produced virus like particles (VLP) copies of the FMD virus in insect cells, requiring less expensive facilities. We have shown for three serotypes that vaccinating cattle with VLP, with enhanced physical stability, can protect from FMD infection. New rapid methods will be developed to design, express and test physically stabilised VLPs for a wide range of strains, to ensure we can produce vaccines for the current needs and newly emerging viruses. This project will allow optimisation of commercial production methods for VLPs to make the vaccines affordable and available for livestock farmers in the poorest regions of the world.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Plasmodium vivax Volunteer Infection Studies in Thailand
Funder: Wellcome Trust

Abstract: Vivax malaria remains a major global health problem. Because of the existence of a hypnozoite stage and the clinical relapses this causes, elimination strategies are more difficult to design and implement successfully than for falciparum malaria. Vaccines and new well-toleratedanti-relapse drugs are badly needed. To accelerate vaccinedevelopment, we will develop and assess the feasibility of conductingPlasmodium vivaxvolunteer infection studiesin Thailand, recruiting semi-immune volunteers from endemic areasrepresentative of target populations for vaccine deployment.We will draw on the participating institutions'expertise in clinical malaria, immunology, entomology, parasitology, volunteer infection studies, and vaccine development. We plan to develop vivax controlled human vivax malaria infectionmodels able to test protective efficacy ofthe pre-erythocytic and blood stage vivax malaria vaccines currently in development. During this programme we plan to conduct six volunteer infection studies, determine immunological correlates of protection, and test four vaccine candidates. The programme will lay the groundwork for developing models to test futuretransmission blocking vaccines and new anti-relapse drugs for radical cure. The volunteer infection studies will be accompanied by a programme of social science and empirical ethics research to assess theiracceptability and the understanding of volunteers, patients, researchers and policy-makers.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: HIC-Vac populating the Global Health Network for VIS studies
Funder: Wellcome Trust

Abstract: This project supports HIC-Vac's aims by developing a community of practice for human challenge researchers on the Global Health Network platform. The Global Health Network (https://tghn.org/) isa facility to support and enhance clinical research in developing countries. They have attracted 11,000 users comprising research staff from 56 developing countries - many of whom are research nurses. It has 37 different communities of practice operating, has had over 10 million views and 300,000 site memberships. Hundreds of thousands of research documents have been downloaded and over 400,000 online courses taken. The site has been successful because it is developed with simple, user-friendly technology and is perceived as an open and trusted space independent of any single institution. This website has proved there is demand for professional networking for researchers in Global Health alongside a trusted source of valid and comprehensive resources, training, tools and guidance. Imperial will create, populate and maintain a dedicated webspace on TGHN for global volunteer infectionstudies.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: A case study on data-sharing in public health emergencies: influenza
Funder: Wellcome Trust

Abstract: It is proposed to assess and review the sharing both of GSD and of other essential data that contribute to risk assessment and intervention for zoonotic influenza viruses. This will include assessing the sharing of Gene Sequence Data in the publically accessible GISAID EpiFlu database, how data are obtained to be used in toolsdeveloped by the Centers for Disease Control and Prevention USA andby WHO for assessing the risks of zoonotic influenza viruses, and how, with this information at hand, the selection and prioritisation of viruses for development as vaccine for pandemic preparedness purposes proceeds.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: INFECTION
Title: Cholera vaccine effectiveness in Nsanje and Chikwawa, Malawi
Funder: Wellcome Trust

Abstract: Following the 2015 oral cholera vaccine (OCV) mass campaign of 160,000 people in Nsanje District, Malawi, the International Vaccine Institute (IVI) was funded to setup diarrheal disease surveillance in Nsanje and adjacent Chikwawa districts. Surveillance is ongoing at22 and 18 health care facilitiesin Nsanje and Chikwawa, respectively. Research activities include to 1) analyse the vaccine effectiveness (VE) in Nsanje, through a 1:4 case-control study and 2) conduct a cost-of-illness study to help estimate OCV cost-effectiveness. The IVI is working in parallel in neighboring Mozambique. Diarrheal disease surveillance is ongoing in the Cuamba study area and an OCV has been conducted in 08/2018. The Mozambique study area borders the Malawian Nsanje/Chikwawa districts. We propose to continue the research in Malawi through extending the surveillance work and the case-control study, to ensure the assessment of long-term VE and cost-effectiveness. Further, the extent of herd protection through OCV needs to be assessed; the Chikwawa setting, after the 2018 OCV campaign constitutes the perfect scenario. The GFTCC is currently preparing a research agenda for "End cholera by 2030" roadmap and the Malawi/Mozambique scenario with surveillance ongoing in both countries, provides an unique opportunity to answer research questions identified through the GFTCC.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Developing the 3-dimensional cellular model of Tuberculosis by integrating co-axial bioelectrospray,technology and stem cells
Funder: Wessex Medical Research

Abstract: TB is still a major global killer. This research will use engineering methods to create a 3D model to assist understanding of how the disease resides in humans and identify new drugs to combat it.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION