NIHRDataInsights/HRCSData huggingface dataset:
Title: Using sequence data to trace the origins of footandmouth disease outbreaks
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description Foot-and-mouth disease (FMD) is an infectious viral disease of cloven-hoofed livestock. The disease remains endemic in many countries in Africa and Asia, from where it continuously threatens the livestock industries in countries that are free of FMD. Such incursions can have dramatic impacts upon agriculture and wider economy of an affected country as was shown during previous outbreaks in the UK. FMD is caused by an RNA virus (FMDV) that exists as seven antigenically distinct serotypes. The genome of FMDV is highly variable and evolves rapidly as a consequence of errors that are introduced and inherited during replication. These characteristics allow nucleotide sequence data to be used to reliably reconstruct the relationship between viruses recovered from different locations, or at different times.At the broadest scale, analyses of sequences can be used to categorise field strains into discrete clades (topotypes) which frequently show geographical clustering based on the historical distribution of the virus, allowing us to precisely characterise new viral isolates and trace their origin and movements across international boundaries. As a recent example, our work (SE2940) has identified and monitored the spread of two different FMDV lineages (within serotypes O and A) that that have emerged from the Indian sub-continent during 2013 and 2015, respectively, to cause outbreaks in North Africa and the Middle East. These unexpected results reinforce the concerns about how readily FMD can pass across international borders, and now raise questions about the heightened risks to the UK as well as the suitability of vaccines that might be used to control outbreaks. At the highest resolution, complete genomes sequences can also be used to define the farm-to-farm level relationships between closely related samples collected during FMD outbreaks. This approach has been pioneered by previously Defra-funded projects (SE2938 and SE2940) for use to support real-time outbreak investigations in the UK (2007) and Bulgaria (2010-11). Such data can play a central role in the event of a future FMD outbreak in the UK, and we are developing bespoke analytical methods and statistical pipelines to improve our confidence in the interpretation of these data Objective [1] Continue to generate real-time molecular epidemiology reports describing field strains currently circulating in FMD endemic countries, [2] Exploit next-generation sequencing approaches to increase our capacity to process the large number of samples that might be received for analysis during a future FMD outbreak,[3] Develop and apply analytical tools and models which combine epidemiological and genetic data to understand the spatial and temporal spread of FMDV[4] Utilize the sequence data to predict antigenic phenotypes


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: INFECTION
Title: Estimating the economic cost of bovine TB incidents on cattle farmers in the High Risk and Edge Areas of England and Wales
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description This study aims to develop a strong set of quantified estimates for the costs to a farm business of bovine TB. This is vital to assess the economic impact this disease has on industry. Defra will use these updated estimates when conducting future cost-benefits analyses of potential bovine TB control policy options, evaluating current policies and to understand the impact of eradicating bovine TB on productivity in the farming industry. This project will update important monetary estimates to help assist economic assessment of future policy development and evaluation for the TB strategy. Objective This study aims to develop a strong set of quantified estimates for the costs to a farm business of bovine TB. This is vital to assess the economic impact this disease has on industry. Defra will use these updated estimates when conducting future cost-benefits analyses of potential bovine TB control policy options, evaluating current policies and to understand the impact of eradicating bovine TB on productivity in the farming industry. This project will update important monetary estimates to help assist economic assessment of future policy development and evaluation for the TB strategy.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: INFECTION
Title: ETHICOBOTS (Ethiopia Control of Bovine Tuberculosis Strategies)
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description This research will allow APHA expertise to contribute to disease control measures to tackle the high burden of bTB in the Ethiopian dairy farm sector and to investigate the consequences of the on-going centrifugal trade of potentially infected dairy cattle to low prevalence regions and farming systems on transmission. The aim is to minimise the zoonotic impact on poor high risk groups, including dairy farm workers and their families and those at risk as the emergent dairy livestock system continues to expand. This interdisciplinary programme addresses poverty and livelihood issues in relation to bTB in a unique manner and builds on previous studies, considering new breeds of cattle. In addition it may provide some insight into better understanding the effects of cattle vaccination upon disease transmssion, which may inform any future cattle vaccination programme in the UK. Objective The main objective of this proposal is to provide a strong scientific understanding for the development of sustainable control strategies for bTB in Ethiopia that could- significantly reduce the high rate of bTB and its zoonotic transfer in the expanding dairy sector, especially to more disadvantaged population sectors- minimise trading of bTB infected dairy cattle to protect the national zebu herd and the livelihood of poor farmers- reduce the risk of zoonosis in high risk populations


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;3.4 VACCINES
Health categories: INFECTION
Title: Mycobacterial determinants of survival and fitness within the bovine host
Funder: Department for Environment, Food and Rural Affairs

Abstract: Bovine tuberculosis (BTB), a disease of cattle caused by Mycobacterium bovis, is a persistent and longstanding problem in the UK. Despite the presence of an expensive test and slaughter control programme (estimated to cost £100 million annually), the disease is spreading in prevalence and geographic area. Vaccination is a promising alternative control strategy but the only available vaccine in the short to medium term is BCG, an attenuated strain of M. bovis. This has variable and low efficacy, therefore a greater understanding of host pathogen interactions are needed in order to design novel and effective control strategies for BTB. The overall goal of this proposal is to identify the bacterial genetic determinants for survival of M. bovis in disease relevant models of natural infection. These include in vitro, ex vivo in bovine alveolar macrophages and in the bovine host. In order to do this we will use Transposon Directed Insertion Seqeuncing (TraDIS methodology). This approach, which has been used successfully in other bacteria, involves the generation of a saturated transposon library of mutants of M. bovis which are then put through selective pressures (e.g. the bovine host). Sequence counts derived from an input pool (no selective pressure) are compared to an output pool (exposed to selective pressure) allowing for the estimation of fitness for each mutant. This work will allow us to identify the genetic requirements for survival of M. bovis in one of its natural hosts thereby providing a fuller understanding of the physiological adaptations M. bovis makes in the host and the nature of the selective pressure. Additionally, identification of the genes that are essential for survival in the bovine host provides an excellent unbiased starting point for the rationale design of new and improved vaccines.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Exploring the richness of Mycobacterium bovis strain diversity to decipher the epidemiology of bovine tuberculosis ecology
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description Undertake a detailed genomic analysis of the diversity of strains of M. bovis found presently and historically in Britain in badgers and cattle, based on Whole Genome Sequencing (WGS) comparing them to the diversity of strains found globally within the Mycobacterium complex, in order to explain the spatio-temporal dynamics of strain types of bovine tuberculosis observed in Britain. Specific objectives• Use the unique archive of M. bovis isolates held within the Animal and Plant Health Agency, from cattle and also from spatially linked cattle and badgers from the randomised badger control trial (RBCT) • Whole genome sequence representative samples over space and time from within the regions in England and Wales where cattle are endemically infected with M. bovis.• Asses the wgs diversity of M. bovis in GB and asses it’s potential for giving greater insights into the epidemiological tracing of bTB Objective The specific objectives of this work are to:- Use the unique archive of M. bovis isolates held within the Animal and Plant Health Agency, from cattle and also fromspatially linked cattle and badgers from the randomised badger control trial (RBCT)- Generate whole genome sequence from representative samples over space and time from within the regions in Englandand Wales where cattle are endemically infected with M. bovis.- Use phylogenetic and phylogeographical analysis to identify patterns of spread of bTB locally (between and within cattleand badgers) and nationally, in particular to provide a finer grain to the genotype analyses that currently inform the controlprogramme (Figure 1).- Develop new methods for the use of WGS to improve the epidemiological tracing of bTB- Use the genetic data from these studies to test hypotheses regarding the critically important issue of on-farm persistenceof bTB.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Phylodynamic analyses of the epidemiology of M. Bovis in Britain and Ireland
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description Bovine TB R&D Programme 2017/18 intend to leverage R&D evidence by contributing to research commissioned by BBSRC which is relevant to TB R&D Programme. In particular we will contribute to research undertaken at Glasgow University entitled ‘Tackling a multi-host pathogen problem - phylodynamic analyses of the epidemiology of M. bovis in Britain and Ireland’ where Whole Genome Sequencing techniques are used to analyse samples collected from cattle and badgers in the UK and Ireland, and the DNA sequences compared. This can be used to assess whether cattle and badgers from the same geographical area are affected by the same strain of TB and to assess the spread of TB strains between geographical areas and across time. Importantly for Defra, this data will be used to inform mathematical models of disease spread in cattle and in badgers, and will be able to inform the current Defra TB Modelling Initiative study (SE3292), to generate a comprehensive model of TB across GB taking into account both cattle and badger aspects. In addition this data will inform the effect of long term culling, as used in Ireland, to assess the benefit of such a policy for TB control in England. Defra will contribute 10% of the total study costs, under the Government Partnership Agreement, thus leveraging at 1:9 ratio to produce data to inform a high priority Defra TB model. Objective •Obj.1. generate M. bovis sequence data over broad geographical scales in RoI in order to describe the spatio-temporal phylogenetic relationship between M. bovis found in cattle and badgers at the farm-to-farm scale (UCD).•Obj.2. quantify the spatial scale at which M. bovis circulates locally in cattle and badgers in RoI (UCD) by mapping phylogenetic data generated from objective 1 onto recorded locations of cattle herds and culled badgers and identifying key statistical metrics for the association. This will be compared to equivalent data from NI and GB (UG, under separately funded project)•Obj.3. compare inter-species mixing between M. bovis strains found in GB, NI and RoI using robust metrics and signatures derived from the M. bovis phylogenies (UCD/UG).•Obj.4. develop network-based models that capture key factors of possible population density dependence and badger perturbation (UG) and cross referenced to more detailed studies of densely sampled badger and cattle-derived populations of M. bovis (identified in Obj.s 2 and 3). •Obj.5. fit the models from Obj. 4 to the epidemiological and genetic data to models of M. bovis transmission in cattle and badgers in RoI, GB and NI (UG).


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Development of a Tuberculin Replacement Test
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description To develop a molecularly defined skin test reagent to replace tuberculin as a surveillance and trade tool, including applicability to the Caudal Fold Test (CFT) by:• Increasing the induced reaction sizes (signal strength) by including additional antigens to the cocktail• Adding of further antigens to the TRT cocktail that complement antigens in DIVA, not only to increase Se overall but increase its robustnessSpecific Objectives:Obj. 1.To define the composition of the optimal skin test antigen cocktail to replace tuberculin.Obj. 2.To establish bio-bank populated by material generated from animals used in this project (sera, PBMC, host DNA, host RNA, host tissues for histology). Objective tbc


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Experimental deign for the study of anthelmintic resistance in UK cattle populations: PhD Project
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description Drug resistance is a worldwide problem in human and animal populations. The animal health industry has historically relied on the use of anthelmintic treatments to control seasonal outbreaks of helminth and nematode diseases in cattle, sheep and goat populations. Over the last 50 years the use of such treatments has become increasingly problematic due to emerging resistance in parasite populations, associated with changes in parasite life cycles in response to global warming, newly prominent species emerging, prohibitively high costs in discovering new treatments and most importantly the suboptimal use of existing treatments. Whilst anthelmintic resistance has been identified in the national UK sheep flock, the situation remains unclear in UK cattle.VMD/Defra Project VM0503 has been conducting field & laboratory studies to evaluate methodologies for the early detection of anthelmintic resistance in cattle in England, and has demonstrated that existing international guidelines for the field evaluation of anthelmintics are insufficiently robust to detect emerging resistance. This PhD project will use VM0503 datasets to explore and develop appropriate statistical methods for the analysis of cattle anthelmintic efficacy data to allow robust field determinations to be made, which will allow policy makers and the broader industry to monitor and respond to emerging resistance issues. The PhD is funded by the Engineering and Physical Sciences Research Council (EPSRC). This research proposal is to cover expert input on anthelmintic resistance and to enable the student to spend time in the field environment. It will facilitate a PhD Management Team (PMT) who will oversee the project and the student development. This team will include the University supervisors and experts. Objective The PhD programme has the following objectives: 1. Critically review existing statistical methods for the analysis of field anthelmintic performance in all species.2. Use representative datasets generated from VM0503 to determine the most appropriate statistical methodologies for analysing such data in cattle.3. Test these methods on all farm datasets and undertake refinement as required.4. Analyse all datasets to determine extent of likely resistance in this 3-year, multi-farm study.5. Formulate robust conclusions on efficacy testing/ resistance study design and statistical analysis.6. Communicate recommended statistical methodologies to be applied in the field environment to COWS, RUMA, AHDA, NOAH and other industry representatives as well as providing guidance to WAAVP working groups on detection of anthelmintic resistance.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Combating avian influenza through systematic analysis of antigenic drift, genetic variation, and development of novel diagnostic tools and vaccines
Funder: Department for International Development

Abstract: The poultry industry in developing countries has made dramatic progress in improving production of animal protein at affordable prices to rapidly expanding populations. However, sustainability of poultry production is threatened by widespread morbidity and mortality due to avian influenza viruses. These viruses cause devastating economic losses and pose risks for zoonotic infections, particularly among poor farmers who work under conditions of low biosecurity. Viral spread can be reduced through mass slaughter and vaccination. However, large scale depopulation of flocks is impractical in developing countries due to its economic and social costs. The effectiveness of both diagnostics and vaccines have been compromised due to rapid evolution of these viruses, and in many regions, multiple divergent strains co-circulate, thereby requiring broadly cross-reactive vaccines and vigilant surveillance to inform vaccine strain matching. Similarly, diagnostics may lose their effectiveness as the viruses evolve. The present proposal aims to bring together expertise in the UK, Vietnam and Pakistan to develop novel vaccines and diagnostics that are tailor-made to protect against AIVs currently circulating in Vietnam and Pakistan. This will be achieved through a multifaceted approach to select optimal, broadly cross-protective antigens, develop recombinant multivalent vaccines that protect against both AIV as well as other endemic production diseases (duck plague and Marek's disease), and complementary rapid pen-side diagnostics. Detailed assessments to evaluate how the novel vaccines and diagnostics benefit stakeholder populations will be conducted at different levels of the value chain. Field trials, case studies, community-based activities, and modeling efforts will improve our understanding of the socio-economic impacts of both AIV, and the optimal use of different control strategies to protect farmer livelihoods, public health, and food security.


Research activity codes: 3.4 VACCINES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Epidemiology and evolution of zoonotic schistosomiasis in a changing world
Funder: Department for International Development

Abstract: Schistosomiasis is a disease caused by different species of parasitic worms, called schistosomes. It is a Neglected Tropical Disease (NTD) of profound medical and veterinary importance, inflicting unnecessary suffering on poor rural communities in many parts of the developing world, with the greatest burden within sub-Saharan Africa (SSA). Recent changes in selective pressures following, for instance, new dam constructions/irrigation systems and/or altered agricultural practices, combined with increased mass drug administration programmes, may all impact the availability of suitable definitive and intermediate hosts for schistosomes, and hence potential for both intra- and inter-specific interactions within such hosts. Furthermore, when humans and their livestock come into closer water contact, novel zoonotic hybrid schistosome species may evolve and establish as a consequence, with subsequent changes in parasite life history traits, transmission potential, morbidity profiles and intervention success. Empirical studies of such potential evolutionary changes under natural conditions are lacking. The research proposed here will contribute to the major push to control and eliminate schistosomiasis as a public health problem as recently put forward in the WHO NTD roadmap. It is essential to discover fully the extent of schistosome zoonotic infections as this may well influence progress in reducing transmission in many regions of West Africa in addition to Niger and Senegal. We hope to learn lessons that will inform and guide future control activities and assist local livestock farmers. Very little attention has been paid to the impact of animal schistosomiasis on domestic ruminants in SSA and in the vast majority of rural settings little is done in the way of treatment. Our findings will play a significant role in helping to control this debilitating disease that is so commonly associated with impoverished rural populations.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: DOSA - Diagnostics for One Health and User Driven Solutions for AMR
Funder: Economic and Social Research Council

Abstract: Microbial pathogens resistance to antibiotics is a major challenge to societies around the globe. Microbes are becoming resistant to antibiotics rapidly to due to variety human action i.e., unnecessary prescription in healthcare, blanket prescription in agriculture and careless release of antibiotics into the environment. Lack of appropriate diagnostic methods is one of the major reasons for in appropriate and overuse of antibiotics. In this project, led by the University of Edinburgh and the IIT Delhi, researchers from India and UK with background in social sciences, technology innovation, and experts in different community settings come together to jointly address this issue. They plan to study current practices, user behaviors, social and economic reasons behind antibiotic consumption in India. Based on a user mapping study, they plan to formulate target product profiles i.e., specification of the diagnostic test for three communities setting. They aim to develop/validate rapid diagnostic assays for three different community settings i.e., urinary tract infections in human health, mastitis (infection of cows' udder) in dairy sector and antibiotics residue detection in water from the environment. Currently, due to lack of appropriate diagnostic technologies, doctors are prescribing broad spectrum antibiotics empirically (i.e. in a trial and error fashion) and farmers are using huge quantities of antibiotics in agriculture and fish farming without appropriate guidance and monitoring. Development of these diagnostic methods will help to reduce the unnecessary consumption, blind prescription and release of antibiotics. An improved diagnostic solution built into health/agriculture and environment settings will help to treat patients effectively and reduce mortality; will help agriculture farmers to get a better economic return for their produce and will reduce resistant transmission. This study brings together an interdisciplinary and international team to learn and support each other towards development of solutions to the global anti-microbial resistance challenge.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION