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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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      "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."],
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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."],
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