NIHRDataInsights/HRCSData huggingface dataset:
Title: Robust Mathematical Modelling of Household-Stratified Epidemic Time-series
Funder: Engineering and Physical Sciences Research Council

Abstract: Infectious diseases affect us all, and are one of the main risks to human health and quality of life worldwide. Despite advances in our understanding of them, a great many questions remain about the way in which infectious diseases actually transmit through human populations. Some open questions, even for common diseases like influenza, relate to estimation of quite basic quantities: how infectious is the illness in different contexts; how long cases of different ages are infectious for; and how much immunity to re-infection is conferred upon recovery. Other more fundamental questions relate to more subtle issues. Many human pathogen species are differentiated into strains that can be identified using modern laboratory techniques, but the way that these interact with each other - for example, whether previous infection with one strain confers immunity to another - is complex and hard to determine. At the same time, the relationship between severity of illness, and how infectious as case is, can be quite complex. Answering these and other questions requires study of disease transmission in a natural setting, but simply measuring the amount of illness in a population does not yield sufficient information to resolve them. Conducting a household cohort study, which involves measuring infections in several whole households over time, offers the promise of much more information. Such studies are being run with increasing frequency. This project is about developing the mathematics needed to analyse household cohort studies in a way that extracts as much novel epidemiological information as possible. There are several steps to be taken: a first question might be how likely a given set of study results are to be observed if we knew every relevant quantity. By creating methods to calculate such a quantity efficiently on a computer, it can become possible to invert the process and gain insight into the epidemiological mechanisms that generate the data. Ultimately, by knowing more about the way in which diseases spread through the human population, we can improve our control of them. For example, if new cases of a disease do not become infectious for several days, then this gives time for quarantine to be an effective control measure. If within-household transmission is much more intense than between-household transmission, then interventions should be focused on the household.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: INFECTION
Title: Epidemic inverse problems: geometry and sampling
Funder: Engineering and Physical Sciences Research Council

Abstract: Imagine an epidemic is doubling in size every six days soon after the first cases are announced. If you know cases are all infectious for six days then a back-of-the envelope calculation tells you that each case infects on average a further three before recovering and vaccine coverage of 67% or greater is needed to contain the outbreak. But if you don't know anything about how long people with the disease are contagious for, then this simple calculation cannot be made without additional information. This project aims to quantify that uncertainty, so that when a measurement of the duration of infectiousness is made then we will be able to assess how infectious the disease associated with a particular outbreak is likely to be. Also, when you have a cold then it is is convenient to describe your disease state 'categorically', which is to say that you will say "I'm coming down with a cold", "I'm in the middle of a cold", or "I'm just getting better from a cold", rather than "my viral titre is probably 3 on a logarithmic scale". It is also often convenient for scientific epidemiologists to take a categorical approach to disease state, and this project proposes to find a reliable method for deciding what the relevant categories should be.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: INFECTION
Title: New vaccine adjuvants from metal organic frameworks
Funder: Engineering and Physical Sciences Research Council

Abstract: Prophylactic vaccination is arguably the most effective medical intervention ever developed, saving some 3 million lives per year. A vaccine is a preparation that causes an individual to develop effective biological defence mechanisms (immunity) against a pathogen. Most often, vaccination is used to protect against an infectious disease, though cancers are also increasingly being targeted. Typically a vaccine will contain a small amount of a material which resembles a disease-causing agent (the 'antigen' - a viral, microbial or tumour component), but does not carry an infectious risk. The vaccine causes the immune system to recognize the antigen as foreign, eliminate it, and "remember" it, thereby conferring effective immunity against the pathogen. In order to ensure that robust immunity is inculcated, an "adjuvant" is usually added to vaccines to mimic the danger signals that naturally trigger immune responses. At present, inorganic compounds known as 'alums' (usually either AlOOH or amorphous aluminium hydroxyphosphate) are used as adjuvants in the majority of cases. 'Alum' can lead to strong immunity to microbes and larger parasites, but does not provoke the necessary immune response to overcome viral infections or the majority of cancers. There is at present a lack of alternative adjuvants able to drive such responses; in this work, we seek to redress this deficiency. Recent work has established that a family of inorganic materials known as layered double hydroxides can act as potent adjuvants whose immunogenicity can be systematically varied through control of their physicochemical properties. In this work, we will explore the metal organic framework (MOF) family of materials. MOFs are a class of materials containing metal centres connected in three dimensions by organic linkers. They have enormous structural diversity, and commonly contain empty 'pores' into which antigens may be incorporated. MOFs have successfully been used for drug delivery and other biomedical applications. They have however never been explored for use as adjuvants. We will systematically synthesise three sets of MOFs (known materials, known materials with immunogenic moieties embedded, and MOFs where the organic linker is immunogenic) and investigate the immune response to these in vitro. This work will be complemented with a detailed systems-level study looking to draw correlations between the materials' physicochemical properties and the immune responses they invoke.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: The politics of knowledge and information sharing across borders: Infectious Disease Surveillance in the Mekong region
Funder: Economic and Social Research Council

Abstract: There is growing awareness that transnational expert networks can contribute to improved health and human development, with the potential to address many challenges that increasingly transcend national boundaries, such as infectious disease control and environmental issues. In recent years, particular emphasis has been placed on networks for South-South cooperation, understood as a process whereby two or more developing countries pursue their individual or collective development through cooperative exchange of knowledge, skills, resources and technical expertise. Indeed, it is recognised that this approach can contribute not only to more sustainable pathways to development, but can also produce knowledge that is better suited to local contexts, as well as positive externalities such as political stability, enhanced sense of ownership, self-reliance and independence. Yet, researchers who have begun to examine the actual working of such networks have identified problems that may hinder effective and meaningful cooperation, including issues of influence, trust, power, cross-cultural communication, and differential access to resources. This project aims to gain a better understanding of these issues and the ways in which they may affect knowledge exchange and network dynamics. As a case study, the project will examine disease surveillance networks in the Mekong basin of Southeast Asia - a region that has been the target of innovative experiments in international health and development, in a context of rapid economic changes. This project also aims to have a tangible public health impact. The Mekong Region is a vital economic resource for the livelihood of rural communities in Southeast Asia, characterised by intense mobility of migrant workers and traded goods. It is also a hotspot of severe epidemics, including multidrug-resistant malaria and avian influenza, with high mortality and morbidity rates throughout the region, significant effects on national economies, and important implications for global health. Despite sustained efforts at the regional level, key problems remain such as the lack of effective channels for rapid communication and coordination in the event of cross-border outbreaks. The detailed study of regional cooperation will provide indications to inform the design and implementation of improved regional programmes, including advice on how to achieve more efficient allocation of scarce resources.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: INFECTION
Title: Contagion: transforming social analysis and method
Funder: Economic and Social Research Council

Abstract: From pandemics and bank runs to gangnam style, we live in contagious times, where society is continually re-composed and even decomposed through its contacts, imitative relations and vibratory events - and these in turn can both generate and be responsive to large amounts of digital trace data. As a result, there's a conceptual and methodological challenge, to effectively re-tool social science, to hone its capacity for influencing behaviour and informing interventions, by strategically and intelligently mining new data resources in order to build an empirically rich and theoretically informed epidemiology of the social. What makes some things, viruses or affects, affective? What gives them a propensity to move, transform and infect? Can we reach some conclusions on transmissibility, its spatial and temporal variations? And what effects, if any, do different contagious domains have on our understanding of this social epidemiology? In the social sciences we haven't as yet capitalised on the possibilities of bringing these resources together to inform a critical approach to reality mining. To that end we contagion invloves an international and interdisciplinary team working collaboratively to explore 3 contagious phenomena, in order to refine methods, explore spatial analysis and theory, to compare contagious domains and identify avenues for further work and impact. The three phenomena are: food scares, influenza events and financial contagion. Each of these is associated with large data sets that not only help us to access transmission but are also part and parcel of the contagious phenomena themselves. So a food scare event is relayed on micro-blogging sites like twitter and achieves an affective valency that might other have been impossible. Moreover, this affective state can transform the contagious event, prompting network changes, behaviours and so on. This project will analyse these kinds of events and their social and spatial character, through geographically and time stamped 'twitter' data. Similarly, we can now explore the evolution of flu lineages through large data sets and link these to our understanding of changes in human/ animal interfaces. Finally, the project will explore the use of social media data use within in the commercial sector and in finance. The design and use of sentiment analysis to measure mood and in turn to adjust trading behaviour (either automated or otherwise) provides a fascinating case of the use of big data to influence behaviour and perform network effects. The project will use these disparate contagious domains to investigate the degree to which contagion is conceptually suited to describing such a seemingly wide ranging if potentially over-lapping set of phenomena.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: INFECTION
Title: Development of a synbiotic for prophylactic and therapeutic use in Clostridium difficile-associated diarrhoea
Funder: Chief Scientist Office (Scotland)

Abstract: Non-digestible oligosaccharide prebiotics stimulate the growth of beneficial colonic microorganisms such as bifidobacteria and lactobacilli. Bifidobacteria are not antagonistic towards the gut pathogen Clostridium difficile, but some lactobacilli have been shown to be inhibitory in vitro, suggesting that they may be able to protect against Clostridium difficile-associated diarrhoea (CDAD) in patients receiving antibiotic therapy. Antibiotics are normally used to treat nosocomial C. difficile infections, but in many cases, they do not prevent relapse, while some eradicate protective bacterial communities, exacerbating the problem. Studies show that certain probiotic lactobacilli can grow on inulin and/or fructo-oligosaccharide prebiotics, and that they suppress growth of C. difficile. The aim of this investigation is to develop and test probiotic/prebiotic combinations (synbiotics) that effectively prevent growth and toxin formation by C. difficile in colon model systems Synbiotics could form the basis of powerful adjunct therapies for augmenting current hygiene programmes in hospitals aimed at reducing CDAD.


Research activity codes: 5.1 PHARMACEUTICALS;3.4 VACCINES
Health categories: INFECTION
Title: MICAP: Microbiological Investigation of Community Acquired Pneumonia
Funder: Chief Scientist Office (Scotland)

Abstract: This project aims to translate advances in molecular technology into tools for rapid bacterial diagnosis in patients hospitalised with Community Acquired Pneumonia (CAP). Faster and more sensitive diagnosis of the causes of CAPby molecular methods will help to reduce the unnecessary use of broad-spectrum antibiotics which lead to Clostridium difficile infection, emerging antibiotic resistant pathogens and drug toxicity. Current diagnostic methods for respiratory bacteria lag behind the molecular diagnostic tools used for respiratory viruses. Phase one of the project is to develop suitable molecular assays. Phase two is to compare the sensitivity of these new assays with the current methods used to detect bacteria, in a clinically well-described cohort of patients presenting to hospital with CAP.The findings of this study will form the basis for a future randomised clinical trial to assess the benefits of using molecular diagnosis as part of a decision-making algorithm for patients with CAP.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: The epidemiology of community acquired Methicillin Resistant Staphylococcus aureus (MRSA) and severe community onset sta
Funder: Medical Research Council

Abstract: Background There is international concern about the emergence of community acquired MRSA (C-MRSA) and PVL toxin producing strains of staphylococcus aureus. These organisms can spread in community settings causing severe skin and soft tissue infections and life threatening infections such as staphylococcal pneumonia. Typically they affect healthy children and adults. Although C-MRSA has become an important problem in some parts of the US the size of the problem in the UK is unknown and the epidemiology is poorly described. Over the last decade there has been a marked unexplained increase in hospital admissions for severe staphylococcal infections that could be caused by C-MRSA and/or PVL-positive strains. Aims and Objectives This research aims to describe the epidemiology of C-MRSA, investigate the increase in admissions for severe staphylococcal infections and describe the extent to which C-MRSA and PVL-positive strains cause severe boils and abscesses. Design. A national case control study of C-MRSA. Case control studies of severe community onset staphylococcal infection. A survey of staphylococcal strains causing severe boils/abscesses. Methodology. C-MRSA case control study - Cases: patients with C-MRSA identified via the HPA Staphylococcal Reference Unit. Controls: community controls identified from GP registers. Risk factors will be ascertained by postal questionnaire. The study will identify which groups are at risk for C-MRSA. Severe staphylococcal infection case control studies. These will be conducted using Hospital Episode Statistics Data and data from the General Practice research Database. They will describe risk factors for severe staphylococcal infection. Survey of staphylococcal strains causing severe boils/abscess. Clinical teams who routinely submit swabs from drained boils/abscesses will be identified. Microbiologist who identify staphylococcus aurues from these samples will refer organsims to the staphylococcal reference Unit (250 isolates). All organisms will be subjected to a PCR toxin gene detection screen and PCR MecA screen. Methicillin resistant strains will be fully characterised to determine if they are the strain types associated with C-MRSA. The prevalence of PVL-positive strains and C-MRSA strains amongst organisms causing severe boils/abscesses will be described. Scientific and Medical Opportunities. MRSA has already become an enormous health issue in hospitals. New strains of toxin-producing MRSA which can spread in the community and cause severe disease in healthy children and adults present a major potential threat to public health. There is a need to understand the extent of the problem and risk factors in order to inform control strategies.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: MRC Centre for Genomics and Global Health
Funder: Medical Research Council

Abstract: The mission of this Translational Centre is to translate state-of-the-art research on human and pathogen genome variation into large-scale clinical and epidemiological investigations of practical relevance for global health. We will develop informatic systems and data-sharing standards to integrate clinical and epidemiological studies at the MRC Laboratories in The Gambia, the KEMRI/Wellcome Unit in Kenya and the Wellcome Units in Vietnam and Thailand, with high-throughput genome technologies, bioinformatics and statistical genetics at Oxford University and the Sanger Institute. We will use these systems to accelerate vaccine development and to tackle drug resistance in malaria by investigating the clinical and biological consequences of variations in the human genome and in the Plasmodium falciparum genome in malaria-exposed populations. The systems and tools that we develop will also support genome research on other diseases that are being investigated in the Gambian, Kenyan, Vietnamese and Thai units, including influenza, enteric bacteria, tuberculosis, HIV/AIDS, dengue, chlamydia, bacterial meningitis and pneumococcal disease.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: Structural and functional studies in lentivirus RNA encapsidation
Funder: Medical Research Council

Abstract: HIV, the causative agent of AIDS, is a retrovirus and during viral assembly it must identify and capture its capped, polyadenylated genomic RNA from the background excess of cellular RNAs and encapsidate it specifically. Ours and others? previous studies have given us considerable insight into this process at a structural and mechanistic level. It is a critical stage in the virus life cycle involving highly conserved RNA and protein motifs and hence is susceptible to therapeutic intervention. Packaging inhibitors would also potentially generate an element of autovaccinatory immune response against the host?s repertoire of viral variants. Packaging involves interaction of the Gag polyprotein of the virus with a conserved RNA structure (the packaging signal - psi). It is becoming clear that a number of cellular chaperone molecules are involved and that the RNA must travel along a very specific route in the cell, probably involving the centrosome, to be encapsidated efficiently. We will investigate the HIV genomic RNA packaging process. We will use novel chemical structural biological methods including oligonucleotide structure probing by FRET and two colour coincidence detection, to analyse:- three dimensional psi RNA structures, the changes in RNA structure involved in capture and the stoichiometry of Gag interactions with the RNA packaging signal. These will be combined with classical 2D (biochemical probing) and 3D (crystallography, NMR) methods and structural predictive methodology. We will also study the process of RNA capture within the cell, the pathway along which the RNA must travel to be encapsidated and the cellular chaperones involved. We will probe the molecular interactions involved with subcellular fractionation and mass spectroscopy and with siRNA knockdown. We will use targeted oligonucleotides to probe these interactions and confirm their importance and to identify therapeutic targets. These studies will unravel a critical process in HIV assembly which has a potentially high therapeutic index for antiviral intervention. We will also translate the findings into better design of lentiviral vectors which should enhance their efficiency and lead to better clinical tools for diagnostic and therapeutic uses.


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