NIHRDataInsights/HRCSData huggingface dataset:
Title: Developing Novel Molecular Assays to aid the Diagnosis of Invasive Fungal Disease by Aspergillus spp, Fusarium spp and Mucormycotina.
Funder: Department of Health (England)

Abstract: Laboratory diagnosis of invasive fungal infection (IFI) has improved with the introduction of molecular assays in our UKCMN reference laboratory. Building on our expertise we aim to further optimise DNA extraction from a range of clinical specimens. Current DNA targets will be evaluated with emphasis on the intergenic spacer (ITS) regions of the ribosomal RNA gene, a target known to facilitate species level identification. These findings will be translated into a standardised pan-fungal real-time PCR assay for introduction into our diagnostic service. The ITS region will form the foundation for designing two novel molecular assays; DNA microarray and fluorescence in situ hybridisation (FISH). In contrast we will also investigate proteomics, specifically MALDI-TOF mass spectrometry, for the identification of filamentous fungi. From a database of profiles we will use genus and species specific moieties for identification. The aim is to decrease the time taken for diagnosis of IFI improving clinical outcome.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Clostridium difficile subtypes related to severe disease, mortality and clustering and their association with phylogenomic variations within the organism.
Funder: Department of Health (England)

Abstract: Clostridium difficile is a leading cause of hospital-acquired infection (HAI), causes severe disease and imposes a significant financial burden on healthcare. The current method of ribotyping isolates is very subjective and is unable to identify true clusters associated with outbreaks and severe disease. The aim is to identify specific subtypes associated with increased virulence and transmissibility and to investigate associated genetic variation. The proposed research will establish multilocus variable-number tandem-repeat analysis (MLVA), a more discriminatory method of typing that will subtype known ribotypes implicated in outbreaks and severe disease. After analysing clinical patient data together with ribotypes and MLVA subtypes, selected isolates will be subjected to further molecular investigation i.e. genome sequencing and mutant analysis. By identifying these strains early in infection will allow for aggressive patient therapy and outbreak management, which will improve patient care and decrease healthcare costs.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Use of bacteriophages to reduce the carrier state and the rate of nosocomial infections with multi-resistant Gram-negative bacteria
Funder: Division for Social Care and Health Research (Wales)

Abstract: Antibiotic resistance is one of the greatest medical challenges of our day. Currently we are observing the emergence of cross class antibiotic resistance that results in limited treatment options and increasingly in un-treatable bacterial infections. This is exemplified by NDM-1, a community acquired resistance mechanism that is already estimated to be carried as normal flora by 100 million people in East Asia and is rapidly emerging in the UK. NDM-1 and similar resistance mechanisms are spread by promiscuous plasmids. Bacteriophage naturally destroy bacteria. We propose to isolate and characterize specific bacteriophage that target plasmid transfer systems We have a large strain collection of multi-drug resistant bacteria which will be used to select a panel of lytic phage targeting the transfer systems by counter selection against non-plasmid carrying strains. These will be used in surface disinfection of hospital environments and also to eliminate the carrier state by oral administration. Phage are licensed for Listeria eradication in food products and have been used in patients. The advantage of our approach is that it specifically targets antibiotic resistant bacteria and the major mechanism driving their dissemination. The strategy is to cleanse environments and patients of resistant bacteria and thus enhance standard antibiotic therapy


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: Rapid detection and treatment of ventilator-associated pneumonia towards improved antibiotic stewardship.
Funder: Department of Health (England)

Abstract: Critically ill patients whose lungs are supported by breathing machines (ventilators) commonly develop new lung infection, called ventilator-associated pneumonia (VAP). Because VAP is often fatal, antibiotics are administered whenever it is suspected. However VAP is hard to distinguish from several non-infective lung conditions and most patients with suspected VAP do not have pneumonia. Therefore many patients receive unnecessary antibiotics for several days, promoting emergence of superbugs'. Laboratory infection results for VAP typically return in 3 days. A simple test rapidly and confidently excluding VAP would improve patient care, reduce unnecessary antibiotics and decrease costs. We recently showed that low levels of specific proteins in fluid from the lungs of patients with suspected VAP effectively excluded VAP within 4 hours. The test used is an extension of existing technology produced by our commercial partner Becton Dickinson (BD) Biosciences. Our test will be rigorously analysed in a clinical trial and if rapid, safe, cost-effective reductions in unnecessary antibiotics are confirmed the test will be rapidly introduced into hospitals through the commercialisation expertise of our technology transfer team and BD Biosciences. Every intensive care unit worldwide deals with suspected VAP, and our test would have significant global healthcare impact.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Translating whole genome sequence technology into diagnostic and public health microbiology.
Funder: Department of Health (England)

Abstract: An effective programme of surveillance is required to control infectious diseases. This includes tracking of disease trends, identification of new infectious disease threats and detection of serious outbreaks. An important component of this detective work is to be able to type the causative pathogens. Accurate typing would allow strains to be compared to confirm whether or not an outbreak involving spread of a particular strain is occurring, and could be used as an early warning system to detect the spread of certain strains of clinical importance (e.g. particularly antibiotic-resistant or virulent) through the population. Unfortunately, there is a technology gap in that the methods available to type pathogens are not sufficiently discriminatory to determine with a high degree of accuracy whether strains of the same species are closely related or not. Our research group contains representatives of the Health Protection Agency (HPA), a large NHS Trust and the Welcome Trust Sanger Institute the largest genome sequencing centre in the UK. We aim to work together to develop a technological solution based on the comparison of bacteria by comparing the sequence of their entire genome. We aim to make this as straightforward as possible to perform, so that the technology can be introduced into diagnostic and public health laboratories across the UK where it will provide information in real time on bacterial spread and outbreaks in hospitals and the community.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: InfeCtion respONse through vIrus genomiCs (ICONIC)
Funder: Department of Health (England)

Abstract: a) Unmet need Viruses are common causes of severe disease, and virus infections are majorly disruptive to hospitals and the community. Currently available NHS laboratory tests are unable to help identify how these viruses have been spread, or introduced into the hospital (e.g. from another hospital patient or someone from outside), or whether a virus has become resistant to some antiviral drugs. Our proposal aims to develop the methods to answer these questions. HICF T5 Full Application (HEI) Page 14 of 158 CLOSING DATE: 13th JAN 2012 b) Technology for development We will develop a novel set of methods to obtain the genetic sequence of viruses from patients. This will be done from samples routinely taken from individuals for diagnoses. In view of the huge amount of information generated by gene sequencing, bespoke methods will be developed for curating and linking such information to other important clinical data, such as symptoms, as well as age and geographic location. c) Key goals and deliverables We focus on viruses of major importance to individuals and the population. Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) are major causes of disease and death. Noroviruses are a very contagious cause of diarrhoea and vomiting, and often are spread in hospitals. Influenza is a common viral infection, which often leads to major epidemics and even pandemics. Measles is a classical childhood infection, yet continues to spread amongst young people due to inadequate immunisation rates. d) Healthcare impact The outcome of our research will directly help doctors to improve the treatment of those with HIV and HCV. It will ensure that hospitals respond more appropriately to cases of norovirus in its wards, to limit spread to others. Finally, our public health response to outbreaks of influenza and measles will be made more effective at limiting on going spread of these viruses in the population.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Fully integrated, real-time detection, diagnosis and control of community diarrhoeal disease clusters and outbreaks.
Funder: Department of Health (England)

Abstract: Seventeen million people suffer a diarrhoeal disease every year. These diseases often lead to outbreaks of infections, like norovirus - now among the costliest infectious burdens on the NHS. The sooner diseases are detected, the sooner they can be brought under control - limiting their health and financial impact. We know from outbreaks of Escherichia coli O104 in Germany and O157 at Godstone Farm in Surrey that surveillance is key to detection; but with fewer people now consulting their GP over diarrhoea, outbreaks are increasingly tricky to detect using traditional methods. This hides the true burden of disease. We will use data from multiple sources to scout for infection in the community, take samples and analyse them, using modern technology to detect organisms We will analyse the DNA of microbes to discover which family of organisms they belong to and how they are evolving. Since many diarrhoeal diseases can pass between humans and animals we will develop and integrate veterinary and medical surveillance. Our goal is an integrated real-time, surveillance/diagnosis/investigation system - centred on the patient - that detects community outbreaks sooner, enables Health Protection professionals and Environmental Health Officers to intervene quickly and thus lessen short- and long-term harm.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Implementation of microbial whole-genome sequencing for individual patient care, local outbreak recognition and national surveillance.
Funder: Department of Health (England)

Abstract: Currently, laboratories have to use different methods to identify every different bacterium that could cause a patient's infection, to find out which drugs that bug is resistant to and whether it is particularly nasty (like the super-bug MRSA ). This is very labour-intensive and slow. In theory, each bacterium's genetic code could provide the same information faster without needing special systems for each bug. We plan to work out how to use all the letters of each bug's genes to transform the way routine NHS laboratories work. This means finding out the best way to use small desktop machines to get the genetic data in local hospitals, and writing software to manage the data and present results to doctors and nurses in ways that are easy to understand, so they can instinctively use them to manage patients better. The project aims to show that this can all happen in a local lab fast enough (within a day) and cheaply enough to improve patient outcomes e.g. by getting more appropriate drugs faster. We also want to show it would save the NHS money if implemented across the UK and that the system can easily be extended to include new bugs


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: GADSA: gamified Antimicrobial Stewardship (AMS) decision support app for prescribing behaviour change
Funder: Arts and Humanities Research Council

Abstract: Antimicrobial resistance is a global problem. Implementing appropriate antimicrobial prescribing policies and stewardship in clinical and community healthcare settings is one of the powerful ways to reduce antibiotics overuse. This is of great importance in Nigeria and other Low and Middle Income countries (LMIC) where clinical practice is less regulated. In these countries, due to resource constraints, a widespread over the counter availability of antibiotics and counterfeits create a very challenging environment for implementing antimicrobial stewardship. The Infection Control Africa Network (ICAN), with 28 African member states, has launched the Antimicrobial Stewardship Education Initiative in July 2016 to tackle this issue across the continent. The aim of this interdisciplinary project is to investigate the use of gamified apps on mobile phones and tablets for changing prescription rates through improving compliance with prudent antimicrobial prescription policies, supporting professionals in prescription decision making around three key conditions (urinary tract infections, single dose surgical prophylaxis and upper respiratory track infections). Based on previous study with ICAN and the international Infection Control Resource (iNRIC, www.nric,org,uk) delivering policies and guidance to infection professionals at the point of care, it was identified that African experts preferred accessing policies in a graphical gamified format over their mobile devices compared to text-based guidelines. The app will be co-authored and developed jointly with healthcare professionals from two settings (national teaching hospital in Lagos and a community hospital) and evaluated to assess usability and prescribing behaviour change over a period of 3 months. The cutting edge game-based training technology will enable a customisation support to localize the gamified app to new settings by healthcare professionals themselves. This pilot will demonstrate a new innovation approach with a potential to be cost-effectively scaled up and expanded to cover other AMS policies and settings to support professionals across ICAN member states across the African continent. Our multi-disciplinary team, consisting of computer scientists, epidemiologiest, infection control experts , and a behavioural scientist is ideally placed to develop an app based AMS intervention. We have expertise in app development, AMS guideline translation, and behaviour change, ideally placing us to deliver the proposed programme of work. Moreover, we will co-design our app with users in Nigeria, utilising our existing partnership with ICAN and The College of Medicine of the University of Lagos - affiliated to the national Lagos University Teaching Hospital (LUTH) and regional Obafemi Awolowo University hospital.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: INFECTION
Title: A one health approach to the investigation and control of MERS-CoV among camel and human populations in Jordan as a potential model for the region
Funder: Arts and Humanities Research Council

Abstract: A stratified multi-stage cross-sectional survey will be conducted among Bedouin communities and their camels in the southern governorates of Jordan (Aqaba & Ma'an) during the period April 2017 to April 2018. These governorates have been selected due to their high number of camel owners, long porous border with Saudi Arabia to the south and already established RVC relationships. Camel owning households and and non-camel owning households will be randomly selected in a 4:1 ratio using local government data of registered livestock owners. Blood samples and oral and nasal swabs will be collected from all family members and a physical examination performed. A pre-tested, structured questionnaire to identify risk factors for MERS-CoV infection will also be administered at this time. Based on an expected prevalence of 4% MERS-CoV seroprevalence among camel owning households and a 0.5% expected seroprevalence among non-camel owners (a risk ratio of 8) a 1:4 ratio of camel herders to non-camel herders and an 80% power, with a 90% confidence interval and a design effect of 1.25 to account for clustering - sample size has been calculated as 946 individuals, with 757 camel herders and 189 non-camel herders. Nasal swabs will also be taken from those camels belonging to selected owners. The number of camels to be randomly sampled per herd has been calculated as 11, using an expected prevalence of 15% and a confidence level of 80% and a mean herd size of 12. In herds of less than 11 camels all camels will be tested. Human serum samples will be screened using anti-MERS coronavirus ELISA (IgG) with microneutralization assay performed as confirmatory test. Human nasal and oral swabs, and camel nasal swabs will be tested by PCR to identify MERS-CoV viral RNA. All samples will be shipped to the US and diagnostics performed at NIAD/NIH Virus Ecology Group, Rocky Mountains Laboratories, Montana. Laboratory and risk factor data will then be subject to multivariate statistical analysis.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Hazards Associated with Zoonotic enteric pathogens in Emerging Livestock meat pathways (HAZEL)
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Tanzania has been identified as a hotspot for bacterial foodborne disease due to zoonotic enteric pathogens including non-typhoidal Salmonella and Campylobacter, with livestock (ruminants and poultry) as confirmed source of Campylobacter. Most livestock meat supply chains are informal but commercial supply chains and markets are expanding rapidly to meet growing demand from consumers. Increased industrialisation may affect occurrence of food-borne pathogens, particularly in poorly-managed systems, with risks of product contamination and human infection likely to increase with scaling-up of production systems and increasing complexity of supply chains. This project applies modular process risk modelling (MPRM) to understand and address hazards for human health associated with the specified zoonotic enteric pathogens in emerging livestock meat pathways in Tanzania. The research is multidisciplinary and transnational, engaging expertise from social science, veterinary and human health, conventional microbiology, molecular epidemiology, and statistics and modelling to develop the MPRM. Supply chain mapping, value chain analysis, prevalence and quantitation studies, standardized molecular typing methods, Monte Carlo methods and Bayesian belief networks will be used to support decision-making concerning control points for intervention, and to provide source level inference or biotracing opportunities that complement risk assessments. By collaborating with an East African human diarrhoeal disease surveillance system, preliminary source attribution may be possible. Finally, policy scientists will conduct systematic reviews of national and international regulations and policy as well as key informant interviews to identify strengths, weaknesses, opportunities, and threats (SWOT) in current Tanzanian food safety policy. SWOT analysis will be informed by MPRM findings to identify gaps and suggest improvements to national, regional, and international food safety policies.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Social, Economic and Environmental Drivers of Zoonoses in Tanzania (SEEDZ)
Funder: Biotechnology and Biological Sciences Research Council

Abstract: This project will examine and assess drivers, risks and impacts of zoonotic diseases - brucellosis, Q fever and Rift Valley Fever - that affect cattle, sheep and goats, and impact on human health, livelihoods and poverty in pastoral and peri-urban communities in Tanzania. The project will use inter-disciplinary methodologies from qualitative social sciences, epidemiology and economics to examine how these drivers influence human behaviour and livestock contact networks, and how these, in turn, affect transmission of zoonotic pathogens from livestock to people. Quantitative and qualitative data pertaining to all these elements will be collected coherently in one geographical system, explicitly integrating network patterns and infection dynamics with human economic incentives and behavioural responses.The research methodology includes: (a) qualitative social science and GIS studies to identify and assess drivers of change in livestock systems; (b) cross-sectional epidemiological studies to determine pathogen exposure patterns in linked human and livestock populations; (c) quantitative and qualitative analyses to identify risk factors for transmission in different communities; (d) analyses of household survey data to link serology with livestock reproductive disease and human disease syndromes (febrile illness, reproductive disease, joint pain) and analysis of confirmed human cases across pastoral and peri-urban sites; (e) development of compartmental network disease models and agent-based simulations that incorporate human behaviour and economics; (f) development of household-level economic models and qualitative social autopsies to determine disease impact on family income and livelihoods; (g) model simulations to evaluate the effectiveness of intervention strategies, and qualitative methods to understand factors affecting acceptability of interventions, with engagement of policy-makers throughout the project to support uptake of findings.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: INFECTION