NIHRDataInsights/HRCSData huggingface dataset:
Title: Integrated management-based approach for surveillance and control of zoonoses in emerging livestock systems: South East Asia Pig & Poultry Partnership
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Increasing consumption of meat in developing countries, especially in SE Asia, is leading to new demands on pig and poultry supply chains and emergence of new production networks. The zoonotic threats posed by these changes are largely unknown. The project will deliver interdisciplinary understanding of interactions between (1) meat production, the environment and supply practices, (2) socio-economic and export pressures, cultural understandings and perceptions of risk to humans and livestock, and (3) the infection dynamics and diversity of zoonotic infections and antimicrobial resistance determinants in these systems. This understanding will provide baseline knowledge and inform the design and evaluation of interventions intended to strengthen the safety and robustness of meat supply chains in ways that build on existing formal and informal practices and contexts, implementable in dynamic SE Asian settings.Our aim is to exploit interdisciplinary expertise including social, biological, and governmental players from Myanmar, Viet Nam and UK to bring about step changes in pro-poor control measures using knowledge-driven and culturally relevant strategies that concomitantly improve animal health and productivity and thus improve and protect human health. The objectives to achieve this aim involve parallel work in Viet Nam and Myanmar:(1) To characterise pig and poultry production systems and supply chains.(2) To characterise key stakeholders' existing perceptions and practices related to livestock disease, zoonotic risk and baseline preventive mechanisms.(3) To identify the impact of different livestock systems on the prevalence and diversity of bacterial zoonotic infections and on antimicrobial resistance.(4) To up-scale regionally accessible diagnostic laboratories(5) To identify, pilot and evaluate appropriate and effective knowledge-based training programmes in ELS in Viet Nam and Myanmar, and consider how these might be translated to other contexts.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Zoonoses in Livestock in Kenya (ZooLINK)
Funder: Biotechnology and Biological Sciences Research Council

Abstract: We will establish an enhanced zoonotic disease surveillance system in an area of western Kenya where we have prior evidence of a substantial burden of zoonotic and food-borne diseases. This will involve the development of mobile phone-based data collection tools and training of staff in their use. At the same time we will assess the operation, performance and costs of existing surveillance activities.We will deploy diagnostic tests for 14 different zoonotic pathogens, plus common coinfections, in both humans and livestock. We will also develop new multiplex systems using bead-based technologies and paper-based assays (as a longer term goal aimed at point-of-decision diagnosis).We will screen 7500 livestock at markets and slaughterhouses, and 5000 humans reporting to health care facilities with suspected zoonotic disease, to obtain baseline epidemiological data on the prevalence/incidence of zoonotic infections in the study populations. We will identify risk factors in individuals and at specific locations. There will be more detailed studies of a subset of individuals (600 per species) in a case-control format; for humans this will include trace-back to residence. For cattle and pigs the subset will be genotyped using state-of-the-art SNP chips, primarily to establish ancestry and estimate levels of introgression. We will develop a risk network model of zoonotic disease distribution in different species and locations, parameterised from and validated against the field data. The models will be used to test different ways of allocating resources to surveillance, by species and location, in order to maximise cost-effectiveness (as DALY-weighted numbers of cases detected).We will develop projections of demographic and agricultural changes, particularly trends towards the commercialisation and intensification of livestock production, and use the risk network model to estimate consequent changes in zoonotic disease risk and economic burden.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: INFECTION
Title: Machine-learning to predict and understand the zoonotic threat of E. coli O157 isolates
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Enterohaemorrhagic E. coli (EHEC) O157 lysogenized with Shiga toxin 2a (Stx2a)-encoding bacteriophages have become prevalent in cattle in the UK in the last 30 years and this timeframe matches the emergence of serious EHEC-associated human disease. Cattle are an asymptomatic primary reservoir for this zoonosis which can cause bloody diarrhoea and kidney/brain damage in humans. Whole genome sequencing has demonstrated the mosaic nature of the E. coli O157 genome and multiple prophages contribute to diversity of this serotype. Based on whole genome sequences, we have recently used support vector machine, a machine-learning algorithm, to predict the zoonotic potential of cattle isolates. The main conclusion was that only a small fraction of the bovine isolates (<10%) may be a threat to human health, even within previously defined pathogenic lineages. The prediction probabilities are based primarily on prophage-associated differential protein variants (PVs) extracted from sequence assemblies. The proposed study will combine bioinformatics and laboratory research to define key prophage regions important for prediction and investigate how they impact on pathogen biology. The computer-based studies will focus on in silico recombination, decision trees/random forests and genetic algorithms to define critical combinations of PVs. The laboratory work will initially study paired isolates with similar core genomes but markedly different prediction scores. Transcriptomic analysis, metabolic profiling, Shiga toxin production, cellular interactions and toxin pathology in a mouse model will be studied. Isogenic mutants of prophage regions identified by the bioinformatics analyses will then be characterised in the same laboratory assays. The research aims to identify differential genes responsible for zoonotic potential and use this information to simplify assessment of farm isolates to allow targeted interventions.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Building Out Vector-borne diseases in sub-Saharan Africa: the BOVA Network
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Despite major reductions in malaria in sub-Saharan Africa (SSA) in the past 15 years, malaria continues to be a major burden on health with 114 million people infected, 191 million clinical malaria cases and 394,000 deaths in the region in 2015. The scale of the rise in Aedes-borne diseases in SSA is uncertain, not least because until relatively recently most febrile illnesses were considered to be malaria. Today there is a growing recognition of the threat from Aedes-borne diseases including yellow fever, dengue, Zika and chikungunya. Since over 80% of malaria transmission in SSA occurs indoors, and Aedes-borne diseases are transmitted in and around the house by vectors that lay their eggs in water bodies indoors and outdoors, the focus of the Network will be on developing ways of screening houses from mosquitoes and building environments inimical to vectors. To achieve this we will bring together two disparate communities: experts on vector-borne diseases and the built environment. Our Management Board is unique in having a broad range of experts from both disciplines, and from SSA and developed countries. This Board will oversee a range of activities namely: (1) information exchange, (2) pump-priming research in the control of vector-borne diseases and the built environment, (3) capacity building in this area and (4) advocacy to reach out and expand the network in order to build a new scientific discipline and ensure its sustainability. There has never been a better time to develop this Network since it is essential to support the World Health Organisation's (WHO) new global strategy on vector control that has building inter-sectoral collaboration between the health sector and other sectors as one of its four central action pillars. In this strategy the need for strengthening collaboration between these sectors is key. Thus, if funded, the Network would be at the forefront of WHO's Global Vector Control Response and will help protect the health of millions.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Genetic & Symbiont Strategies for Controlling Vector Borne Disease
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The network focuses on two highly promising new approaches for controlling vector-borne disease: genetic modification and the use of heritable endosymbionts. Both require the rearing and release of insect disease vectors with the aim of suppressing their populations or blocking the transmission of pathogens. They are highly targeted, species specific strategies, which (depending on the specific form employed) may only require one short intervention phase rather than repeated applications, thus providing major advantages over insecticides in terms of environmental impact and cost effectiveness. Some, for example Wolbachia, are already starting to be deployed in a number of countries. This Network aims to draw together individuals from a broad range of scientific disciplines engaged in developing and deploying these approaches to foster knowledge exchange, methodological and technological sharing, and stimulate innovative collaborative research projects that provide a foundation for new approaches or would allow more effective implementation. Importantly, given the potential impact of these approaches in developing countries, this Network will help to consolidate and expand the links between leading UK scientists and excellent researchers based in disease-endemic countries. The themes to be covered by the network will be: vector-pathogen interactions; genetic modification technologies; gene drive systems; sterility and sex determination; Wolbachia and virus transmission blocking; other endosymbionts and parasite transmission blocking; vector population biology / male ecology and behaviour; population modelling; best practise for community engagement and field release trials; and impact assessment and cost-benefit analyses. This will be a fully open network, open to new members throughout, and we will actively seek to recruit new expertise into the field to complement that of the starting group of members.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION)
Health categories: INFECTION
Title: The development of a phage food additive with the aim to control Salmonella in swine and poultry
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Animal experimental design to study the role of phage therapy in acute-non typhoidal Salmonellosis Co-investigator: Dr. Parameth Thiennimitr, M.D.,Ph.D. Address: Department of Microbiology, Faculty of Medicine, Chiang Mai University Species of animal: 6-8 weeks old female mouse (Mus musculus) C57BL6 strain Protocol (in brief): C57BL/6 mice will be purchased from Nomura Siam International. Mice will be acclimatized for at least 1 week before the experiment day. 24 hour before Salmonella enterica Typhimurium (strain IR715) infection, mouse will be orally gavaged with 20 mg streptomycin sulphate to allow subsequent STM IR715 to establish a colitis. Streptomycin-treated mice will be orally infected with 100 microlitr of 109 cfu/ml STM IR715 solution. Then, 100 microlitr of Salmonella phage solution will be orally gavaged to the infected mice for consecutively 3 days. On day 4 post infection, mice will be euthanized by CO2 and cervical dislocation. Mouse colon content, colon, spleen will be collected for further analysis. Control group (no treatment) of mice will be orally fed with normal saline solution as used as a vehicle for the experimental (phage therapy) groups. Animal protocol approval committee: All animal experiments conduct at Chiang Mai University will be approved by the Chiang Mai University Animal Care and Use Committee (CMU-ACUC). All animal experiments will be performed in the AAALAC-certified biosafety level (BSL) 2 facility located in Chiang Mai University. Numbers of animal in each group is 7. [Calculated followed Bernard, R. (2000). Fundamentals of biostatistics (5th ed). Duxbery: Thomson learning, 308, level of significance = 0.05)]


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: Development of single-cell sequencing technology for microbial populations
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Next-generation sequencing has enabled routine sequencing of bacterial isolates for national epidemiological surveillance programs is becoming more common. This has led to significant advances in relating bacterial pathogenicity to disease etiology and their combined impact to human health and food security. Standard sequencing techniques, however, rely on the bulk sequencing of cultured samples and as such do not fully resolve the genetic heterogeneity of bacterial communities. High-throughput single-cell sequencing approaches have the potential to rectify this and elucidate the mechanisms operating within these communities as they evolve under varying modes of selection. However, the majority of single-cell technology to date has focussed on eukaryotic systems, and solutions dedicated to microbial systems remain an unmet need. The long term aim is to establish methods to observe the genotypes and transcriptional phenotypes of mixed microbial populations including heterogeneity of genotype from clonally derived populations under selection, and the transcriptome heterogeneity arising from naturally occuring epigenetic mechanisms. The proposed experiments are based on preliminary data that indicate that defined mixed species populations can be sorted by FACS for conventional single-cell DNA sequencing. By developing FACS-based methods for microbial isolation along with combinatorial indexing and sequencing, we will enable robust, high-throughput approaches for bacterial analysis. We will use microbial mock community samples for technology development but aim subsequently to address short, but related Biological Objectives to demonstrate the real-world applicability of the methods develop. We will examine genomic heterogeneity in hypermutator strains of Salmonella enterica under selectionunder selection from subinhibitory concentrations of antibiotics give rise to heterogeneity of transcription within populations of Salmonella


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: INFECTION
Title: Animal Husbandry, Prescribing Practices and the Control of Veterinary Medicines and AMR in Colombia's 'Livestock Revolution'
Funder: Biotechnology and Biological Sciences Research Council

Abstract: In common with many low- and middle-income countries, Colombia has seen sharp rises in livestock production in response to rapidly growing domestic demand for food of animal origins. While this 'livestock revolution' promises to enhance food security, reduce poverty, and improve rural livelihoods, there are also questions about its sustainability and wider implications for human and environmental health. Expanding livestock production is associated with a host of negative impacts on biodiversity, carbon emissions, water availability and quality. As livestock numbers have risen globally, so too has the use of antibiotics and other veterinary medicines (VM) in animal husbandry. VM has been instrumental in reducing the global burden of livestock disease and delivering the productivity increases necessary to meet the rising demand for food globally, but the World Health Organization (2012) warns that the scale and nature of antibiotic usage in livestock production poses major risks to both human and animal health. As well as undermining food safety and environmental quality through residue contamination, the pervasive use of antibiotics in agriculture creates strong selective pressures favouring the emergence of bacteria that are resistant to antibiotic drugs used for treating disease. Such anti-microbial resistance (AMR) threatens to cast us back into the dark ages of medicine without effective antibiotic treatments. The aim of this proposal is to support international efforts to address the AMR crisis and support poverty alleviation in low- and middle-income countries like Colombia by improving understanding of the behavioural factors influencing the control and use of VM, which is a major contributing factor in the emergence of AMR. To that end it will combine interview, observational, survey, and documentary analysis methods to achieve these more specific research objectives (ROs): RO1. Explore animal husbandry practices and their implications for animal health, farm incomes, use of VM, and AMR risk across two different milk production systems (extensive, dual-purpose, i.e. meat and milk, and intensive & specialised, i.e. milk only) RO2. Analyse prescribing practices and the formal and informal networks through which VMs are sourced, circulate, administered and then accounted by veterinary professionals and by food and pharmaceutical markets RO3. Evaluate the regulatory systems in Colombia for ensuring animal health, food safety, and appropriate prescription and use of VM RO4. Build a wider network to support behavioural change interventions in Colombia and across Latin America for improving the control and use of VM


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;3.4 VACCINES
Health categories: INFECTION
Title: Does AMR in livestock contribute to AMR in people in NE India? An interdisciplinary study.
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Considerable amounts of antibiotics are used in the rearing of livestock and the use of these antibiotics leads to the selection of bacteria that are resistant. There is some evidence that these bacteria may contribute to resistance levels in bacteria that cause human disease. This research aims to investigate if antibiotic resistant strains of bacteria found in farms are also found in cases of human disease in a region of North East India. This project will also record the use of antibiotics on farms, and to investigate the human behavioural and animal health factors that influence antibiotic use. The study combines microbiological and social science research methods. Agriculture in this area consists mainly of smaller livestock enterprises typical of many rural settings in India. The aim is to provide a comprehensive description of the distribution of resistant bacteria in humans, livestock (including aquaculture) and the environment together with a thorough study of the context which leads to the selection of these bacteria in order to understand which antibiotics (and the quantities) are used and why. The project also aims to increase the research capacity in India to continue this work through increased experience and training in the application of DNA sequencing and social science methods for research into antibiotic resistance. The specific research work that will be performed is: 1. Sampling on farms in order to bacteria from animals, people, the environment and retail meat products, together with bacteria from cases of human disease from local hospitals. 2. Collection of data from farms to record antibiotic use, how and why decisions are made to use antibiotics, which individuals are influencing these decisions, and what factors affect the decision-making process (to include how presumptive diagnoses are made, societal hierarchy, prior knowledge, education, attitudes, and economic factors) using established social science research methods . 3. DNA sequencing of the bacteria in order to characterise the mechanisms responsible for antibiotic resistance, and to compare the relatedness of agricultural and hospital bacteria. This enables us to determine if there is transmission of antibiotic resistance from farm animals to people. 4. To develop antibiotic stewardship advice, materials and programmes that are tailored to a rural Indian context in order to maximise animal health and ensure rational use of antibiotics. Good quality scientific evidence is needed to ensure that any restrictions on antibiotic use on farms are rational, and targeted appropriately. Regardless of any contribution to human antibiotic resistance better antibiotic stewardship in agriculture will reduced levels of resistance in livestock and lead to improved animal health.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Understanding the ABCs of multi drug resistance - tying the knot on the antibacterial peptide ABC transporter McjD
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The overall aim of this proposal is to gain a detailed insight in the molecular mechanism of antibacterial peptide and multi drug exporters. This study will also allows us to gain a very detailed picture on the ligand recognition by ABC exporters. ABC exporters are powered by the hydrolysis of ATP and transport their substrate via the alternating access mechanism with a twist. There is little structural information on this important class of exporters. We have selected the novel antibacterial peptide ABC exporter McjD to expand our knowledge and we have solved the structure of McjD at 2.7 Å resolution. The structure is in a novel conformation for ABC exporters, nucleotide bound outward occluded. The structure represents an intermediate between outward- and inward-facing states. We propose that the initial driving force from an outward to inward state is proton driven rather than ATP dependent. We have reconstituted McjD in proteoliposomes and it retains its ATPase activity; its ligand, MccJ25, can induce the ATPase activity. We want to study how McjD recognises its substrate by NMR. In light of the new conformation we want to further characterise the new state by mutagenesis, PELDOR and X-ray crystallography. We have identified residues in the transmembrane region that form salt-bridges and we propose to disrupt them and measure their ability to transport its ligand in proteoliposomes. We want to investigate the conformational changes associated with ATP hydrolysis. We have already obtained initial crystals and the structure shows that upon ATP hydrolysis the two nucleotide binding domains have separated; unexpectedly the transmembrane domain is still in an occluded state. We want to optimise these crystals in order to build a reliable model for the post-hydrolysis state. We will also combine PELDOR measurements in bicelles to measure specific distances and compare them to the crystal structure.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION