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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. 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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. 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"reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"], "title_narrative":["Capacity building in dietary monitoring and public health nutrition in the Eastern Mediterranean Region Countries"], "description_narrative":["In common with many Western countries, the Eastern Mediterranean Region (EMR) has a major problem with obesity and the associated public health issues. The World Health Organization (WHO) has been developing new health policies to lower intakes of sugar, saturated fats, trans fats and salt with the aim of reducing the risk of non-communicable diseases (diabetes, cardiovascular disease and obesity) in children and adults. To implement these policies successfully it is essential to have high quality food composition and food intake data to underpin research into the links between diet and health and to enable effective dietary monitoring and policy development. Most EMR countries use international food composition tables that include foods consumed in western diets with different nutrient composition, especially for mixed and traditional dishes. Some of these data from other countries are outdated and do not reflect the composition of foods currently consumed in EMR countries, meaning that calculated nutrient intakes are inaccurate. Methods of measuring dietary intake also need to be up-to-date and use appropriate food information. This project intends to provide technical and scientific support for researchers (mainly food and nutrition experts) in LMIC countries in the EMR, and will also provide training in the use of improved standardized methods for production and management of food composition and food intake data and also identify appropriate biological markers of food nutritional value and measurements of health outcomes. A review will be undertaken of food and nutrient intakes in the LMICs to develop strategies for reducing sugary and fatty foods in these diets based on new WHO guidelines. The Quadram Bioscience Institute, that aims to develop solutions to worldwide challenges in human health, food and infectious disease and non communicable disease, will lead the project in partnership with the WHO EMR office. The latter will help to coordinate and co-align regional activities to ensure public health priorities are targeted effectively. Three main activities will underpin capacity building in the EMR with a focus on 10 target LMICs (Morocco, Tunisia, Egypt, Jordan, Palestine, Sudan, Lebanon, Pakistan, Iran & Afghanistan). The project will build on existing links with the WHO EMR and will develop and extend activities with LMIC in the EMR. Four main activities are planned: (1) Training and knowledge exchange workshops; (2) Short-term exchanges of researchers; (3) Development and application of harmonised protocols for pilot sample collection, food analysis, data generation and creation of online regional food composition datasets; (4) Development of possible dietary and other strategies to support reduction in intake of sugary and fatty foods. The main outcomes will be to build capacity and practical skills in the LMIC to improve production, management and use of food composition and dietary intake data, and biomarkers. Knowledge of European and International standards will be disseminated, with support from WHO, to experts across the region. Networks of expertise within the region will also be an important outcome leading to increased collaboration and effective data sharing. The project will enable more efficient use of better quality, region specific, food composition and intake data that can be used for research, monitoring and policy development. This will benefit LMICs in the region by providing data and tools that can encourage reduction of sugar, saturated fat, trans fats and salt and thereby reduce the incidence of diet related disease.","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. 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