NIHRDataInsights/HRCSData huggingface dataset:
Title: Using spatial statistics and genomics to develop epidemiologically relevant definitions of insecticide resistance in African Malaria Vectors
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Malaria is a major cause of mortality and morbidity in Sub-Saharan Africa (SSA) and one of the biggest impediments to economic development. Malaria control is threatened by insecticide resistance which demands improved insecticide resistance management (IRM). Molecular markers could greatly aid improved IRM, but are currently underused. Our proposal will develop and train control programme linked SSA vector biologists to design and analyse genomic data to assess Anopheles population structure and to identify resistance-linked genetic variation. The overarching aim is to develop a nucleus of SSA scientists best able to exploit the power of whole genome sequencing to address questions of public health importance. Using the key phenotype of insecticide resistance as an exemplar we will: 1. develop and implement standardised, server-based pipelines for the analysis of whole genome sequence data to identify patterns of population structure, genetic diversity and insecticide resistance candidate genes/variants 2. develop spatially- and temporally-explicit sampling frameworks for malaria vectors to permit local-scale genetic tracking and prediction of (i) population connectivity, (ii) temporal stability and (iii) insecticide resistance. 3. test extant and novel DNA markers for prediction of resistance in females of malaria transmission age


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: INFECTION
Title: A vector excreta surveillance system (VESS) to support the rapid detection of vector-borne diseases
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The emergence of outbreaks of preventable vector borne diseases has inspired us to develop an early response tool for the detection of human blood-borne pathogens from the mosquito population. We have developed a novel method to collect the excreta and faeces (E/F) from large pools of mosquitoes for the purposes of pathogen surveillance. We have successfully amplified DNA of filarial and protozoan parasites from the E/F of vectors and non-vectors exposed to moderate infections in blood. Benefits of the vector excreta surveillance system (VESS) include opportunities to integrate surveillance of many blood-borne pathogens through a non-invasive sampling technique which can be coupled with existing, disease-specific mosquito collections. Our first aim it to field test the approach in our study site in western Ghana to detect malaria which is highly endemic and filariasis which is nearing elimination (2% prevalence) from a previous high endemicity. We will employ a Latin square design of three mosquito collection methods rotated among 8 households randomly chosen across four village habitats. In addition we will collect outdoor resting mosquitoes as they enter and leave the village from the breeding sites. We will compare Plasmodium spp and Wuchereria bancrofti infection prevalence from the E/F of pooled mosquitoes with the infection prevalence in mosquito carcasses. We will compare detection of pooled E/F between a field-friendly mini-PCR with test-strip visualisation to the standard quantitative PCR. Our second aim will be to determine the limits of detection to other important vector-borne pathogens: trypanosomes and the arboviruses West Nile, dengue, chikungunya and Zika. This will be done through lab-based exposures using vector and non-vector species to determine the optimum methods of detection post-exposure.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Rapid diagnosis of onchocerciasis using urinary biomarkers
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Onchocerciasis or river blindness is a parasitic disease affecting 17 million in sub-Saharan Africa. It causes visual impairment and severe dermatitis. The symptoms of the disease can be controlled by annual treatment with ivermectin, which kills the larval stages in the skin, but the adult worms are not eliminated and can survive for more than 10 years. For decades, diagnosis of onchocerciasis has relied on microscopic examination of skin biopsies for the first-stage larvae (microfilariae) of Onchocerca volvulus. This is an invasive procedure that is increasingly being met by non-compliance in endemic communities. Moreover, annual ivermectin treatments that are administered to prevent disease symptoms kill the microfilariae but do not eliminate the long-lived adult worms. Thus, skin snips are becoming less sensitive for diagnosis, and a non-invasive diagnostic test that could detect a single viable adult female worm would revolutionise the field. Applying tandem mass spectrometry and next-generation sequencing, we have recently identified proteins and small RNAs released by O. volvulus in patient urine specimens. These molecules appear to be associated with extracellular vesicles. In this proposal, we will investigate the biomarker potential of these molecules by treating cattle infected with the closest relative of O. volvulus, O. ochengi, with drugs targeting the adult worms. We will isolate extracellular vesicles, characterise the protein and small RNA content of parasite-derived material, and explore methods to enrich for biomarkers as a prelude towards a field-deployable urine test for human use. Through our overseas partners, we will also examine human urine specimens (both from infected patients from endemic communities, and from participants in clinical trials for drugs targeting the adult worms) for O. volvulus-derived biomarkers. The cattle samples will serve as validated controls for loss of the biomarkers from urine once the adult worms are killed.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Human Decoy Trap; operational and social acceptability of novel tool to improve surveillance and control of mosquitoes and other disease vectors
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Current vector monitoring tools have not been standardised to sample effectively indoors and outdoors and epidemiologically relevant metrics do not index well against the gold standard Human Landing Catch (HLC). Additionally, the HLC method is increasingly prohibited as it exposes field technicians to pathogens via potential mosquito bites. We have developed a behaviour-based mosquito trap, using olfactory, visual and thermal stimuli to attract host-seeking female mosquitoes. The Human Decoy Trap (HDT) catches mosquitoes on an adhesive surface as they land, preliminary data showing HDT catches up to 10 x more Anopheles mosquitoes than HLCs and up to 5 x the number of other mosquito genera. These results indicate the HDT could be used for monitoring and suggests potential for an outdoor mosquito control method. We will test the HDT to determine how well it samples mosquito diversity, abundance, parasite rate and age in comparison to the HLC, CDC Light Trap and Suna Trap. We will compare results indoors, where the majority of malaria transmission takes place, and outdoors, where we have a poor understanding of transmission, and throughout the seasons in rural savannah and rice irrigation areas (Burkina Faso), coastal urban communities (Benin) and a low seasonal transmission setting (Cameroon), to provide data for comparison of trap performance in a range of malaria settings. We will conduct a Participatory Technology Assessment with field technicians and at-risk communities to understand perceptions and needs regarding mosquito monitoring and control tools and acceptability of the HDT. This will provide design recommendations for future iterations of the trap, which can be incorporated into a standardised prototype to be developed with a commercial partner, enhancing the likelihood of successful adoption of the HDT for basic vector research and applied surveillance, and providing preliminary data for the role of the HDT as an outdoor-based mosquito control device.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Developing a strategy for cysticercosis control in Rwanda, to reduce the burden of epilepsy
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Neurocysticercosis from pig tapeworm infection is the leading cause of preventable epilepsy, causing around 30% of epilepsy in endemic areas, with a high burden of disease in sub-Saharan Africa. Tools for effective control are now available. Rwanda provides an excellent opportunity for control, but there is almost no information on the prevalence and distribution of infection, nor the economics of pig production, in the country. Our aims are to: (1) collect baseline data on the pig value chain in Rwanda, to understand the stakeholders in and governance of pig production. Interviews, questionnaires and market research will be used in formal value chain mapping approach. (2) assess the prevalence of infection in pork entering the food chain, and the prevalence of human and porcine cysticercosis across the country. We will use a stratified random sampling approach to estimate infection in different pig production systems and geographic areas. Cysticercosis in humans and pigs will be detected by antigen ELISA, with confirmation in selected pigs by carcass dissection and species-specific PCR. (3) identify risk factors for infection in a high prevalence area. Risk factors for human cysticercosis and taeniosis (diagnosed by faecal egg counts and copro-antigen ELISA) will be assessed by household questionnaire in a total population survey. Potential risk factors will include demography, sanitation, socioeconomic status (using a wealth index), diet (consumption and cooking of pork), previous anthelminthic treatment and knowledge of the parasite. Households will also be georeferenced, and remote-sensed environmental data obtained. (4) Finally, we will use these data to develop a control strategy for porcine and human infection, and establish a partnership for disease control. This will include developing enterprise models for market-based initiatives, such as premium markets for certified infection-free meat, together with mass chemotherapy approaches.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: INFECTION
Title: Development of a new tool for malaria mosquito surveillance to improve vector control
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Malaria transmission is influenced not only by vector abundance, but as well by demographic traits such as vector species and age structure, as these influence the intensity by which the disease is transmitted. Measuring these traits and the susceptibility to insecticide in natural mosquito populations is key to implement vector control strategies. Currently, methods to measure all these traits are expensive and time consuming and cannot be combined to simultaneously measure them in individual mosquitoes. Here we propose to develop a rapid and cost effective tool based on mid-infrared spectroscopy (MIRS) analysis to simultaneously determine these traits in malaria vectors to facilitate large scale surveillance of wild populations. Specifically, we aim to develop this technology to determine: 1- The species and age 2- Insecticide resistance status The methodology is based on the MIRS measurement of the amount of light absorbed by the mosquito cuticle. As cuticular composition changes during mosquito ageing, differs between species and is influenced by insecticide resistance status, we will use the MIR spectra to predict these traits. Specifically, using computational analysis based on neural networks, we will analyse the complexity of the spectra variations associated with specific traits to make accurate predictions. We will use MIRS to measure different malaria mosquito species with different traits under laboratory settings to develop predictive algorithms; afterwards we will optimize the tool incorporating spectra from natural mosquitoes collected from the field in collaboration with African malaria vector control leading institutions. The development of tool in partnerships with African researchers will directly enable the direct integration of this technology into large scale vector surveillance programmes, enabling critically important insights to assist the control of malaria vectors.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: VAccine deveLopment for complex Intracellular neglecteD pAThogEns (VALIDATE)
Funder: Biotechnology and Biological Sciences Research Council

Abstract: For several complex intracellular pathogens, we have an incomplete understanding of protective immunity. These diseases, including TB, leprosy, leishmaniasis and melioidosis, disproportionately affect LMICs and are often neglected due to the poor predicted commercial return and marginalisation of affected populations. The current linear approaches, which identify a component of the immune response, induce it by vaccination and evaluate efficacy in animal models and clinical trials, are flawed and have proven inefficient for intracellular pathogens. In this Network we will adopt an iterative approach and develop accurate working models of immunity by repeated integration of data from human experimental studies and animal models across the different pathogens. Veterinary vaccinologists and large animal models will facilitate the One Health agenda, and experimental medicine studies and LMIC and industrial partners will ensure relevance and translational value. The smaller animal models will provide the tools with which to easily dissect mechanisms and immune pathways. The integrated approach incorporates in-silico and in-vitro tools to delineate mechanisms, that will feed directly into vaccine design and development. This Network will provide a unique opportunity to bring together individuals working on four exemplar complex intracellular pathogens (M.tb, M.leprae, Leishmania spp. and B.pseudomallei), which share a common lifestyle as pathogens of macrophages, induce similar end-stage pathologies (granulomatous inflammation, tissue remodeling) and alter host immune and metabolic responses. The horizontal collaborations established throughout this network, together with the provision of a protected environment for early data sharing, will exploit the biological synergies. By interrogating mechanisms that lead from infection to disease, we plan to uncover common approaches to inform vaccine development strategies for these and other complex intracellular pathogens.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Social marketing to increase HIV testing for gay and bisexual and other men who have sex with men (MSM) in Greater Glasgow & Clyde: Proposal development work
Funder: Chief Scientist Office, Scotland

Abstract: To end AIDS we need to get more gay men to test for HIV. We just finished a project which examined international studies on mass media interventions to increase HIV testing. We gathered some good ideas about what should work for whom, when and in which circumstances, and we developed an intervention. Given its international roots, we now need to know, with the help of key people and their communities (e.g. gay men and health workers) how this intervention should translate to Scotland in the 21st Century and how we can best evaluate it. This project will then inform a proposal to evaluate the impact of the intervention on HIV testing.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: INFECTION
Title: Optimising Services For People At Highest Risk Of HIV: Developing Best Practice In Delivering HIV Pre-Exposure Prophylaxis(Prep) Through Evaluation Of Early Implementation Across Scotland
Funder: Chief Scientist Office, Scotland

Abstract: Despite major advances in testing and treatment, HIV still has a major impact on individual health and the economy. In July 2017 Scotland was the first country in the UK and one of the few worldwide, to introduce a revolutionary new HIV prevention service known as PrEP (Pre-Exposure Prophylaxis). PrEP involves people at risk of HIV taking anti-HIV drugs to stop them getting HIV. PrEP works well in research trials but we don’t know what happens in the real world when PrEP is given as part of routine NHS care. Clinics offering PrEP already seem much busier and it is possible that there will be more sexually transmitted infections. This is likely to put pressure on already stretched services. This research examines how PrEP has been delivered across Scotland during the first few months of roll out. We will talk to a range of health professionals and people who use HIV prevention services to see what works, what doesn’t work and why. We will combine our findings to make recommendations on the best ways to deliver PrEP for the greatest public good.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: INFECTION
Title: ELVIS Kids: a randomised controlled trial of hypertonic saline nose drops in children with upper respiratory tract infections.
Funder: Chief Scientist Office, Scotland

Abstract: Children have up to 12 viral upper respiratory tract infections (URTI) each year. It isn’t practical to treat each virus individually since over 200 viruses cause URTI. Although most URTI do not result in serious problems, a number spread to the lungs resulting in more serious lower respiratory tract infections (LRTI) such as, such as bronchiolitis or pneumonia, and they can also trigger asthma attacks. Recently, in a clinical trial called ELVIS, we tested a way of treating URTI in adults using salt-water nasal washes and mouth gargles (www.elvisstudy.com). Those using salt water had significant improvement in symptoms. Their symptoms didn’t last as long, they used less over the counter medicines, and they were less likely to pass this infection onto other family members. We also ran several laboratory experiments which showed that salt helps stop the multiplication of various viruses that cause URTI by helping the body’s own in-built capacity to fight viruses. Now we want to carry out a trial on children with URTI suing salt water nose drops to find out if their symptoms improve more quickly, just like in adults and if they shed less virus, transmit less, and if they need less medical attention.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: MIDAS-RTI measuring the impact of improved diagnostics on antimicrobial stewardship in respiratory tract infection
Funder: Chief Scientist Office, Scotland

Abstract: Respiratory tract infection is a very common cause of broad-spectrum antibiotic prescription in hospitals in the UK. Over-use of broad-spectrum antibiotics is a significant problem in healthcare because it drives antibiotic resistance and exposes patients to increased risk of Clostridium difficile (“CDiff”) infection and drug toxicity. Therefore, reducing broad-spectrum antibiotic use is a key target of hospital antimicrobial stewardship programmes. Narrower-spectrum antibiotics can be chosen to treat respiratory tract infection if a specific pathogen is identified by laboratory testing. However, current diagnostic methods are insensitive and in practice, changes in antibiotics rarely occur. We believe that using improved diagnostic tools will help doctors to reduce broad-spectrum antibiotic use in respiratory tract infection. This study aims to use more sensitive and faster tests to rule out infection with so-called “atypical respiratory bacteria” and therefore to avoid unnecessary use of antibiotics such as macrolides in these patients.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Personalised Approach to Pseudomonas aeruginosa (PAPA)
Funder: Cystic Fibrosis Trust

Abstract: Attempt to transform detection, understanding and treatment of Pseudomonas aeruginosa infection.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Epidemiological models for control of arboviral disease for Europe (ARBONET) ANIHWA call3
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description Emerging and re-emerging infectious viral diseases continue to challenge both animal and human health around the world. For Europe, vector-borne infections, such as mosquito-borne West Nile fever (WNF), and Rift Valley fever (RVF) and tick-borne Crimean-Congo hemorrhagic fever (CCHF), pose a continuous risk of incursions or northward expansion from endemic areas. The drivers of these infections are multifactorial and include increased mobility of human populations, increased global trade in live animals and foodstuffs, and climate change affecting the geographic distribution and competence of vectors. In addition, persistent arbovirus infections in wildlife pose unprecedented challenges to formulation of proper surveillance and control actions, due to the complexity of the interfaces between different host populations.The proposed initiative “ARBONET” will be focused on WNF, CCHF and RVF infections, specifically on development of epidemiological models that can inform risk-based surveillance and interventions that can control disease outbreaks in Europe. The major goal of this joint initiative is to create a multidisciplinary research network combining the expertise of veterinary and human epidemiologists, disease modellers, virologists and arthropod biologists to increase knowledge and understanding that will facilitate rapid control of disease outbreaks. Objective The ARBONET proposal has the following specific objectives: 1) to develop epidemiological models of possible scenarios of CCHF, RVF and WNF spread in Europe, evaluating possible risk-based surveillance approaches and control strategies, 2) to promote epidemiological studies on distribution of viral genetic subpopulations, 3) to increase the knowledge of virus-vector and virus-vertebrate host interactions, and 4) to support dissemination of knowledge on the epidemiology, surveillance and control of these diseases.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION