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      "description_narrative":["Parasites are a major cause of disease and production loss in grazing ruminants worldwide, and their control is increasingly challenged by climate change and drug resistance. In resource-poor marginal farming systems, where reliance on livestock for food and income is high, tools for effective parasite control are rarely available to farmers. Chemical inputs are often in limited supply and not optimally applied, and parasites slow growth, reduce milk yield and cause mortality.  This project builds on previous research conducted on targeting treatment within goat herds in Botswana, which showed that simple indices of parasite impact can be used effectively by farmers to target treatments and improve livestock health. Farmers using the system achieved similar improvements as for whole-herd treatment, while using less than a quarter of the treatments. At the same time, research has advanced the capability of computer models to predict infection risk as a function of climate and weather. Application of risk models could enable monitoring and targeted treatment to focus on the most dangerous times, potentially saving labour and reducing unexpected losses. These prediction models have helped farmers in the UK, but have not yet been delivered to farmers in Botswana. Very high mobile phone use in the region provides a potential route to deliver such tools, and to support farmers who are in remote locations and out of the reach of over-stretched animal health extension personnel.  This project will combine targeted treatment and risk prediction to produce an integrated parasite control system that works in the hands of remote marginal farmers in Botswana. Risk predictions will be generated from climate data using existing models, and communicated to farmers by mobile phone. Alerts will prompt trained farmers to check their animals and intervene as needed, feeding back information on animal health status and treatments applied, again by mobile phone. This information will, in turn, help to update risk profiles for a given area. Resources to support application of targeted treatment protocols will be produced and disseminated on a new mobile phone friendly website and in hard copy, including aide memoires and infographics to ensure access regardless of literacy or level of education. Running the system in the field will show that it works, and provide a blueprint and materials to upscale it across a wider area, with the potential for automation in a later translation phase.   The integrated system will be delivered with key partners in Botswana, who have helped to identify the need for this work, and will provide support to the field trials and then to embed the integrated system into existing support structures and training. Project outcomes will be summarised in a policy report and discussed with partners and potential users, to promote wider uptake. Application of improved parasite control in goats and sheep on smallholder farms has the potential to drive step changes in household nutrition and livelihoods across large areas of Africa. Outcomes will be communicated beyond Botswana through existing networks to fully realise these benefits.","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. 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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      "participating_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY","BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL","BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL","QUEEN'S UNIVERSITY BELFAST"],
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      "title_narrative":["A randomized trial to evaluate the toxicity and efficacy of 1200mg and 1800mg rifampicin daily for 4 months in the treatment of pulmonary tuberculosis"],
      "description_narrative":["Approximately 20 million people globally are infected with tuberculosis, and about 1.5 million people die of the disease annually, i.e. one death every 20 seconds. Currently, tuberculosis of the lungs is treated with four drugs ethambutol, isoniazid, rifampicin, and pyrazinamide daily for the first two months, followed by the two drugs isoniazid and rifampicin for the next four months. This drug combination is recommended by the World Health Organisation and is used in most countries of the world.  The combination is highly effective if taken properly, but despite this about 15% patients worldwide are not cured. Factors such as patients not completing the course, missing multiple doses, or taking (or being prescribed) the wrong dose contribute to treatment failure. Although the drugs are free to patients, there is a substantial cost, in terms of time and administration, to both the patient and the treatment services. A recent study by Gospodarevskaya  et al (Int J Tub Lung Dis. 18: 810-817) has found that patients have to terminate productive/economic activities and are often forced to borrow money and/or sell assets to cover cost of treatment, which can amount to more than three-quarters of patients' income, in the last 2 months of treatment. Reducing the duration of treatment should increase the number of people who successfully complete treatment and reduce the cost to them.  A reduction could be achieved in one of two ways: using combinations of the new drugs currently under development, or by using the currently available drugs more effectively. Given the enormous cost and long time required to develop new drugs the second option is attractive. Increasing the dose of one of the currently available drugs may allow the duration of treatment to be shortened in the very near future. Three recently published Phase III trials (RIFAQUIN, ReMOX, OFLOTUB) have failed to demonstarte that treatment shortening can be achieved with the quinolones. hus, the rifamycins offer the best hope if higher doses can be shown to be safe. Rifampicin which is responsible for killing most tuberculosis bacteria, appears to be the best choice since increasing doses of rifampicin increases its ability to kill TB bacilli in vitro and animal studies. A similar result could be obtained in human tuberculosis. However, one concern would be a possible increase in unwanted serious side effects with increasing doses. Liver damage by rifampicin appears to be rare and not connected to dose size. In the RIFATOX Trial, a dose of 1200mg, in 100 patients did not increase its toxicity. The central question this trial aims to answer is therefore: does an increase in the dosage of rifampicin allow us to shorten treatment from 6 to 4 months? We are assessing whether giving double or triple the usual dose of rifampicin (1200mg, or 1800mg rather than 600mg daily) is safe and, when given for 4 months only, will result in relapse rates similar to (or better than) those found in the standard 6 month course of treatment. Patients with newly diagnosed tuberculosis of the lung, who agree to participate and have signed a consent form, will receive either the standard 6 month treatment or a 4 month treatment containing the standard drugs but with a double or triple dose of rifampicin. Treatment allocation will be random. The success of treatment in each method will be closely monitored both clinically and by regular microscopic examination of sputum, and the safety of the increased dose of rifampicin will be monitored clinically and with blood tests. If the trial is successful, it will lead to a shorter treatment course for pulmonary tuberculosis. The expected consequences would be: more patients completing the course and higher rates of cure, reduction in rates of transmission of tuberculosis with fewer people becoming infected, a reduced cost of treatment for both patients and treatment facilities and, perhaps, a reduction in the emergence of bacterial drug resistance.","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":["MRC Centre for Global Infectious Disease Analysis"],
      "description_narrative":["The continuing threat from new infectious diseases has been highlighted in recent years by the emergence of MERS-coronavirus in the Middle East, Ebola in West Africa and Zika in Latin America. Preparing for and responding to such threats is a priority for public health agencies and governments worldwide. Equally importantly, as scientific research delivers new approaches to controlling existing infectious diseases such as malaria, HIV, tuberculosis and polio, there is a need to determine what interventions are likely to work best to limit the disease and illness caused by a specific disease in a particular setting.  In this context, computer modelling of the spread of diseases in populations coupled with scientifically rigorous data analysis have proven themselves as powerful tools for giving insight into how diseases spread and what can be done to limit that control that spread. The Centre for Global Infectious Disease Analysis undertakes research on these scientific methods and applies them to disease threats of concern.   A key feature of the Centre is the close links it has made with with public health agencies - such as the Public Health England, the Centers for Disease Control and Prevention in the US (CDC), and the World Health Organization (WHO) - organisations which have to formulate and implement strategies to control infectious diseases.   Senior scientists in the Centre are world-leaders in infectious disease modelling and analysis. They have broad experience in responding to real epidemics, and undertaking epidemiological research on endemic diseases (such as malaria, HIV, tuberculosis and polio). Their work directly influences disease control policy through the many interactions the Centre has with public health organisations and governments.   Funding provided by MRC and Imperial College has allowed dedicated investment into the development of close collaborative partnerships with PHE, CDC and WHO and governments and research centres in many low and middle income countries (LMICs). We also work closely with other important organisations who work on improving health in LMICs (notably the Bill and Melinda Gates Foundation, The Global Fund and Gavi). With each, our collaborative research has both scientific interest to Centre researchers and contributes to the evidence base for public health decisions. Centre funding supports a core technical capacity available to all projects and pays for dedicated liaison staff who facilitate and enhance our partnerships with major global health organisations and LMICs.   MRC funding has also facilitated a greater focus on collaboration, training and career development within the Centre - training the next generation of quantitative infectious disease epidemiologists. We are also involved in increasing knowledge of advanced modelling methods in public health institutions and the wider infectious disease research community, and so have run a large number of introductory short-courses and workshops (in 13 countries in the last 5 years)  This applied activity depends on more fundamental research undertaken in the Centre on the transmission dynamics of different diseases, how diseases evolve genetically over time, and on analysing new approaches to control or treat diseases. This research is interdisciplinary, with Centre researchers working with leading clinical and experimental scientists around the world.  Continued Centre funding will allow existing partnerships to be sustained and enhanced, and new collaborations with researchers and health agencies in LMICs to be developed. By supporting PhD training and postdoctoral career development, it will also continue to expand the UK skill base in mathematical modelling and advanced analysis applied to health problems. Last, continued MRC support will pump-prime new priority research areas, including work on improving the development of new vaccines and on tackling the global challenge posed by antimicrobial resistance.","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":["Robust Permanent Magnet Beam Delivery Systems for Medical Radiotherapy Linacs"],
      "description_narrative":["This proposal forms part of an initiative to design a linear electron accelerator for radiotherapy where all subsystems will be optimised to ensure it is robust, reliable, cost effective and appropriate for use in challenging environments including developing countries. This project aims to design a beam delivery system (magnetic focusing and steering) which uses modern capabilities in permanent magnets to ensure that a high-quality electron beam can be taken from the source to the x-ray generating target with minimal losses. Replacing some or all of the existing electromagnets with permanent magnets should enable a maintenance-free focusing system which requires very little electricity, which has been highlighted as a barrier to providing this technology in ODA countries. (A few smaller, cheaper and replaceable adjustable electromagnets will be included for fine tuning, which would have minimal power requirements.)","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":["RTT Accelerator Technology Options Study"],
      "description_narrative":["Conventional and commercially available Radiation Therapy (RT) treatment systems utilise S-band linac technologies coupled to magnetron or klystron RF power sources, which invariably entails incorporation of the linac structure inside the rotating gantry for circumferential patient treatment. The theme of this activity is to assess a variety of different linac and RF source configuration options, taking advantage of recent technology developments in frequency ranges outside of the conventional provision. Advances in both Standing Wave and Travelling Wave linac operational performance and solid state, magnetron and klystron RF power delivery capabilities, have the potential to be able to define a new RT system configuration which can not only outperform, but also may offer a simpler, more efficient and robust system integration platform which can be more appropriately applied for ODA country exploitation.","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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