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      "title_narrative":["Unveiling the protein landscape of the African trypanosome cell surface and chasing down potential targets for therapeutic intervention"],
      "description_narrative":["Neglected tropical diseases are a diverse group of diseases that thrive mainly among the poorest of the world's populations. Three of the World Health Organisation's 10 most significant neglected tropical diseases - African trypanosomiasis (also known as sleeping sickness), leishmaniasis, and Chagas' disease - are caused by closely-related single-celled parasites. Human infection with African trypanosomes is brought about when an infected tsetse fly takes a blood meal. Without treatment the disease progresses through general ill health to coma and death. Current drugs in use against trypanosomes are old, toxic and failing due to emergence of resistance. Urgent new research is needed to identify potential new therapeutic options.  An unusual aspect of African trypanosomes is that they multiply in the human blood in full view of the body's defence systems. They do this by periodically changing their cell surface to escape recognition by the host. However, many molecules on the parasite surface perform essential functions and cannot be changed. Trypanosomes place these in a special, protected domain on the cell surface. Identifying surface-exposed invariant molecules and understanding how this protective segregation is maintained are of major scientific interest, as well as of practical utility in uncovering ways in which trypanosomes may be vulnerable to new therapies.  Using a combinatorial approach funded by the MRC, I have previously identified the composition of the African trypanosome cell surface. I now aim to exploit this knowledge to single out those invariant surface molecules that are essential to the survival of the parasite during infection. For this, I propose to harness some of the power of modern DNA sequencing technologies to test which cell surface genes, when silenced, cause the parasite to die inside the host. A similar method will be used to identify not only cell surface genes, but any genes that the parasite uses to maintain the cell surface organisation, which is so critical to escaping the host immune attack.   Finally, I propose to test those surface-exposed molecules for their potential as vaccines. My pilot experiments show that I can use genetically-modified parasite to screen for molecules on the parasite surface that are accessible to the immune system. I propose to develop this assay and test the most promising candidates in an animal model of human disease. The proposed work will increase our understanding of the fundamental biology of a significant human parasite, and also, by exposing essential surface molecules, provide the first steps in developing new treatments.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "title_narrative":["A mathematical modeling framework for tuberculosis burden estimation and economic evaluation of pharmaceutical interventions"],
      "description_narrative":["Tuberculosis (TB) is a major cause of disease and death globally. In 2015, WHO estimated there were 9.6 million TB cases and 1.5 TB deaths. Nearly 500,000 of these cases were resistant to two or more of the main drugs used to treat TB. New drugs, and combinations of drugs, are being developed to treat tuberculosis, as are new vaccines that may protect against disease in adults.  Quantifying the burden of TB is fundamental to understanding its global epidemiology and for making appropriate resource allocation decisions. Most estimates of new TB case numbers each year rely strongly on the number of cases reported by countries in that year to WHO. Unfortunately, one in three TB cases are thought to go either undetected or unreported, so the number of cases reported underestimates the number of new cases. While one can correct for this, it is hard to know exactly how much to adjust the reported numbers. Some countries have good systems for recording causes of deaths, which can be used to estimate the number of deaths caused by TB. Increasingly, large and expensive prevalence surveys are being used to estimate the number of people with active disease in a population. These estimates are less subject to bias, but measure a different quantity. Little work has explored the best way of combining these three data sources.  A major goal of this work is to use mathematical transmission models for burden estimation and provide a unified framework for all data. These models yield the number of new cases, deaths, and also the prevalence of disease. They explicitly represent disease transmission and so introduce a dependence between the number of new cases in different years. These models involve parameters evidenced from previous epidemiological work, but must be calibrated to learn from data on TB reports, deaths and prevalence. Calibration means adjusting imperfectly known model parameters in order to match observed model outputs to the data. This process provides a model that may be used to make predictions about burden, but may also teach us something about the underlying processes. Many of the parameters concerning the epidemiology and disease course of TB are quite uncertain, and this uncertainty is rarely represented fully in models needing calibration, but will be done in this project using statistical techniques that also allow comparison of different models' performance.   TB burden estimation and calibration of transmission models are almost always carried out on a country-by-country basis. Many parameters describing disease progression are likely to be similar in different countries, even if their exact values differ for unknown reasons. Hierarchical modelling techniques allow such parameters to be correlated between countries. This can improve precision, particularly for countries with little data, as estimates can be informed by data from neighbouring countries. I will explore these techniques for the transmission model, and also in statistical modelling aiming to account for the observed patterns of drug-resistance. The transmission model will ultimately be extended to include different types of drug resistance.  As new treatments and vaccines emerge, those with responsibility for public health will want to understand the potential impact these new technologies can have in terms of gains in health, and changes in spending. Producing cost-effectiveness and budget impact evidence requires a model that includes transmission, in order to account for indirect benefits accrued by avoiding secondary cases. We will use our model to provide guidance to decision-makers seeking to maximise health gain with limited resources. We will also analyse sources of uncertainty in the model to identify future research that would have most value in increasing the precision of burden estimates and in reducing decision uncertainty around the introduction of new interventions.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "reporting_org_type_code":"10",
      "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"],
      "title_narrative":["EXTending availability of self-management structured EducatioN programmes for people with type 2 Diabetes in low-to-middle income countries (EXTEND)"],
      "description_narrative":["Type 2 diabetes (T2D) is a long term condition where the body doesn't manage its blood sugars (glucose) properly. This can result in the levels of glucose in the blood being quite high. If the body is exposed to high levels of glucose in the blood for long periods of time it can injure the vascular system - both the large and the delicate blood vessels in the body. This can lead to a number of complications such as blindness, kidney damage, damage to the nerves and heart attacks. It is really important when someone is diagnosed with T2D they are supported and taught how to manage their condition to prevent these complications. Globally, the number of people with T2D is increasing with approximately 415 million people currently living with this condition. Eighty percent of people who have T2D live in low-to-middle income countries. LMICs do not have the financial resources, or infrastructure to effectively manage this increasing patient population specifically as they are already stretched dealing with the infectious diseases that are common in these countries i.e. HIV, TB. Therefore, there is great need for inexpensive but effective treatment options for patients.   Patients with diabetes manage their condition on a daily basis themselves. International experts state that patients with diabetes should be taught how to do this; structured education programmes (SEPs) equip people with diabetes with self-management skills. SEPs have been shown to improve diabetes related outcomes in patients, such as blood glucose and wellbeing. An educated and empowered patient can work more effectively with their doctor to improve and maintain better control of their condition. SEPs are usually delivered to groups of patients in the community by trained non-medical educators and thus are a relatively inexpensive 'therapy'. In the UK researchers have developed and tested a SEP called DESMOND which has been shown to improve well-being, adherence to medication, and weight loss amongst other positive outcomes. DESMOND and is currently delivered in over 100 sites in the UK and is also used in in Southern Ireland, Australia and Qatar. To date no SEPs for diabetes have been tested in LMICs. Therefore, this provides a great opportunity to take a diabetes SEP that is proven to be effective and is widely attended in one country and transfer it to another.   The UK research team in collaboration with clinicians and academics from South Africa, Mozambique and Malawi propose to culturally adapt and translate (linguistic adaptation) the DESMOND programme for use in two LMICs - Mozambique and Malawi. The collaborative will then test the feasibility of the adapted SEP in both locations. Data will be collected on the number of people that are invited, respond to invitation, the number that attended the programme, their diabetes control (using point-of-care-testing), blood pressure and their opinion and experience of the programme. Collectively, this information will be used to help us design a formal study after the end of this programme of work. An SEP adaptation tool-kit (detailed instructions) will be developed so that other organisations can take SEPs that work in one country and adapt it for themselves. An implementation model will also be developed again allowing other organisations/health services to implement - that is make SEPs available on a large and sustainable scale.  Both of these will be freely available for the public. To ensure the success of this work we will work closely with the local diabetes associations, we will train local healthcare professionals and people from the local community to deliver the education which means that they can continue to do so well after the end of this study.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
      "participating_org_ref":["GB-GOV-13","GB-COH-RC000346","GB-COH-RC000346"],
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      "participating_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY","MEDICAL RESEARCH COUNCIL","MEDICAL RESEARCH COUNCIL","UNIVERSITY OF LEICESTER"],
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      "title_narrative":["MICA: Development of new agents for the treatment of cryptosporidiosis"],
      "description_narrative":["A recent clinical study in Africa and South Asia has found that cryptosporidiosis is one of the most significant causes of death and illness from diarrheal diseases amongst children in the developing world. Cryptosporidiosis is caused by a single-celled protozoan parasite; the predominant species infecting humans are called Cryptosporidium hominis and Cryptosporidium parvum. This parasite mainly lives in the cells in the gut wall and has a complex life-cycle. Infection occurs due to consumption of water or food contaminated with the parasites. Parasites are spread from an infected individual through their faeces. In people who are healthy and well nourished, the disease clears naturally within a couple of weeks. However, in people who are malnourished (particularly in young children) and people with an immune system that is not functioning properly (for example HIV/AIDS victims), the disease can have a much more significant impact. It is the major contributor to life-threatening diarrhea in young children, with 2.9-4.7 million cases in children under 24 months in sub-Saharan Africa and the Indian sub-continent, leading to more than 200,000 deaths per year. Cryptosporidiosis is also associated with malnutrition and stunted growth in children and probably causes chronic infections, which last for weeks or months. The only drug registered for the treatment of this disease is nitazoxanide, which is not very effective, especially in those patients who are most severely affected due to a weak immune system and/ or malnutrition.   Therefore there is an urgent need for the development of new drugs to treat: (1) children <24 months, especially those that are malnourished and with chronic diarrhea; and (2) immunocompromised children and adults with advanced AIDS and chronic diarrhea. Cryptosporidium may be the cause of as much as 75% of chronic diarrhea in this patient cohort.   We have discovered some chemical starting points that can be used for a drug discovery programme. We have a series of compounds that kill the parasites and also are very effective in clearing the parasites from rodent models of cryptosporidiosis. The compounds are thought to work through preventing the parasite making proteins. The aim of this project is to take these starting points and optimise them to make a molecule which has the potential to be a drug. This will require us to optimise multiple features of the molecule: its ability to kill the parasite, its ability to reach the sites in the body where the parasite resides without being broken down, and its safety. At the end of this project we hope to have a \"preclinical candidate\". This is a compound that we think should be suitable to enter human clinical trials. The steps after this project, prior to human clinical trials will be to make the compound on a larger scale under properly defined conditions and to carry out formal safety testing.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
      "participating_org_ref":["GB-GOV-13","GB-COH-RC000346","GB-COH-RC000346","GB-SC-015096"],
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      "contact_info_website":["https://www.gov.uk/government/publications/beis-official-development-assistance-research-and-innovation"],
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      "default_lang":"en",
      "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_P014429_1",
      "reporting_org_ref":"GB-GOV-13",
      "reporting_org_type_code":"10",
      "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"],
      "title_narrative":["Strengthening health system delivery and quality: Mechanisms and Effects of Performance Based Financing in the Sub-Saharan context"],
      "description_narrative":["Health care providers can be paid in a variety of ways. They can be given an annual budget for agreeing to provide a service or be paid on the basis of the size of the population covered. Payment according to achievement of specific standards or patient outcomes has been widely applied in the health sector.  Such schemes are called Performance Based Financing. These schemes aim to focus health workers and their managers on specific outcomes and to change the way they behave to improve the quality of health care services and population health. Over 40 low and middle-income countries are currently implementing performance based financing schemes in the health sector. However, to date the focus of researchers and practitioners has been mainly on assessing the short term impact of performance based financing schemes on the performance targets. We understand little about how performance based financing affects health workers and the organisations they work in and how this translates into improvements in service delivery and health outcomes. We also do not know if the effects are sustained over time. The design of performance based financing schemes also varies from place to place and we have limited understanding of the factors that influence this variation nor how this affects the way performance based financing is implemented and its subsequent results. Most evaluations collect data specifically for each project, which limits the range of health outcomes that are considered and makes it difficult to compare across studies.  This research project will engage stakeholders involved in running performance based financing schemes and evaluating them in two countries: Mozambique and Zimbabwe. We will work together to clarify how performance based financing has been conceptualised and implemented in each setting. We will also identify how performance based financing is expected to affect health workers and their work environment to bring about better care, and what elements of performance based financing are most critical.  We will use national level data on health system inputs to examine the effects of performance based financing on the health system over time. We will use data from household Demographic and Health Surveys to examine the effects on health outcomes and on the delivery of services that were not targeted by performance based financing. Finally we will seek to understand how performance based financing brings about changes to service delivery by identifying how and which changes in health system inputs are related to improvements in care delivery. We will also examine how the effects of performance based financing vary according to population and health facility characteristics. Performance based financing is sometimes accompanied by separate efforts to increase access to care and we will examine if this matters. Finally, we will look across the two countries to examine if the way in which the performance based financing scheme is designed affects the results.  The project will support knowledge sharing and learning across institutions in the United Kingdom, Mozambique, Zimbabwe and the wider Sub-Saharan African region.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
      "participating_org_ref":["GB-GOV-13","GB-COH-RC000346","GB-COH-RC000346"],
      "participating_org_role":["1","2","3","4"],
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      "participating_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY","MEDICAL RESEARCH COUNCIL","MEDICAL RESEARCH COUNCIL","LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE"],
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      "contact_info_department_narrative":["General enquiries"],
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      "title_narrative":["A randomized controlled trial of influenza vaccine to prevent adverse vascular events."],
      "description_narrative":["Cardiovascular disease is a leading cause of death globally estimated to be responsible for approximately 17 million deaths annually. Heart disease and stroke account for nearly one third of all deaths and are a major cause of hospitalization. Patients with congestive heart failure (CHF) are at particularly high risk. Clinical trials demonstrate that nearly one third of patients with CHF will experience a myocardial infarction (MI), stroke, or hospitalization for CHF. Observational studies have established an association between influenza infection and major adverse vascular events . It follows that vaccinating such a high risk group as patients with CHF against influenza may prevent adverse vascular events. However, these studies are subject to bias and a well designed clinical trial is needed to test the effect of influenza vaccination on preventing adverse vascular events. The goal of this study is to assess whether inactivated influenza vaccine can reduce adverse vascular events in high risk participants. We will address the question by randomizing patients at high risk for adverse vascular events to either annual inactivated influenza vaccine or to placebo over three influenza seasons. The primary outcome is a composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI), non- fatal stroke, and hospitalization for CHF.  We will enroll 3,500 participants from centres in seven countries: Philippines (the lead centre), Mozambique, Sudan, Uganda, Saudi Arabia, Malaysia, China. This proposed randomized trial has important implications for the management of patients at high risk for major adverse vascular events. Although the influenza vaccine is recommended annually for groups with diabetes and cardiovascular disease in many counties, uptake of these recommendations is relatively low. Cardiologists in most jurisdictions do not routinely recommend annual influenza vaccine for their patients as a strategy to reduce future adverse vascular events such as acute coronary syndrome or stroke. Uptake of influenza vaccine in patients with heart disease varies by country but in INTER-CHF sites (where are trial will be conducted) is 11% on average. Rigorous demonstration of influenza vaccine leading to a reduction in major adverse vascular events would represent a landmark study. We anticipate that such a trial would influence management decisions by physicians for patients at high risk for major vascular events. The effect size we propose testing is comparable to secondary prevention strategies available and given the fact that a vaccine is given once annually it is simple and inexpensive. Given the large burden of disease, the possibility to reduce cardiovascular and stroke related death is a compelling argument for this trial.  If influenza vaccine is shown to reduce adverse vascular events, it will represent an important change in how prevention of adverse vascular events is thought about. The fact that our primary outcome is a composite, including various forms of vascular disease will increase generalizability. The study would be a milestone in contributing to evidence-based clinical as well public health policy.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
      "participating_org_ref":["GB-GOV-13","GB-COH-RC000346","GB-COH-RC000346"],
      "participating_org_role":["1","2","3","4"],
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      "participating_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY","MEDICAL RESEARCH COUNCIL","MEDICAL RESEARCH COUNCIL","MCMASTER UNIVERSITY"],
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