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      "title_narrative":["GCRF Agri-tech Catalyst Seeding Award - NIAB"],
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      "title_narrative":["Understanding and enhancing approaches to quality improvement in small and medium sized private facilities in sub-Saharan Africa"],
      "description_narrative":["The private sector is a major and growing source of treatment in low- and middle-income countries (LMIC), but there is considerable concern about the safety and quality of care. Recent years have seen fast growth in small and medium sized private clinics, but their regulation is often poor, and relatively little is known about the effectiveness of interventions to improve the quality of care they provide. This project aims to address this evidence gap.   The research takes place in the context of an innovative intervention developed by the international NGO PharmAccess that extends the benefits of clinical standards and stepwise certification to small and medium-sized facilities in LMIC, using standards developed with international accreditation bodies. The PharmAccess model seeks to improve the quality of care that facilities provide as well as to shape the broader healthcare and finance markets and policy environment. There are several components to the model. Health facilities are assessed on a set of \"SafeCare\" structural quality standards, trained on quality improvement and business skills, and assisted in the development of a quality and business improvement plan. They receive regular mentoring visits and are also connected with the PharmAccess Medical Credit Fund, a social investment fund which facilitates access to bank loans to finance implementation of the plan. The aim is to create a series of virtuous circles, with improvements in SafeCare assessment scores signalling improved quality of care to individual and institutional purchasers, thus increasing demand for health services; and improved business performance ensuring further access to credit, and the sustainability of quality gains.  The research will begin with an analysis of secondary data collected routinely by PharmAccess in Tanzania and Kenya to date to examine changes in the SafeCare assessment scores over time and factors associated with these changes. We will then undertake a randomised controlled trial to evaluate prospectively the impact on quality of care of the roll out of the PharmAccess model to additional private for-profit and faith-based facilities in Tanzania. The trial will assess the effects of the intervention on the quality of care received by patients through comparison of 120 intervention and 120 control facilities after 2 years of implementation. These data will also be used to assess the relationship between SafeCare assessment scores (which measure availability of inputs such as infrastructure, technology and standard operating procedures) and measures of technical and perceived quality of patient care (which concern the interaction between caregivers and patients). Technical quality will be measured through standardised patients (covert actors) and clinical vignettes (overt role-playing), with perceived quality measured through patient interviews. In addition, in-depth interviews will be conducted in 30 intervention facilities and with 8 implementing staff in Tanzania to assess the perceived benefits and costs of participating in the PharmAccess model, and factors affecting quality improvement and business performance. Finally, 30 national level key informants will be interviewed to explore how the PharmAccess model shapes the market for healthcare and healthcare finance, and the policy environment in both Tanzania and Kenya.  The results are expected to make an important contribution to the evidence base on improving private sector care and to the literature on measuring process quality of patient care. The findings will be of substantial benefit to national and international policy makers and programme managers who are interested in private sector healthcare and health systems strengthening more generally, with important implications for all organisations within the health system that require adherence to quality standards (eg, social health insurance programmes, social franchising programmes, regulatory agencies)","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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      "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":["Holistic Approach To Unravel Antibacterial resistance in East Africa (HATUA)"],
      "description_narrative":["The potential harm that increasing levels of antibacterial resistance (ABR) will have on human health is vast, as a consequence the effects of this will be felt across society and at the economic level. It is predicted that by 2050, 10 million lives per year and a cumulative 100 trillion US Dollars of economic output may be lost worldwide. In order to address this looming problem a co-ordinated global response is required to try and halt the rise of ABR. Efforts are underway to tackle the rise in resistance, however agenda-setting is dominated by High Income Countries (HICs) and may not reflect priorities or needs of Low and Middle Income Countries (LMICs), where the levels of resistance and also the types of disease caused by bacteria may be different.   One of the most vulnerable regions to the increase in antibiotic resistance is Africa where, in comparison to other regions of the world, the burden of infectious diseases is highest. The economic, cultural and ethnic diversity of Africa mean that the problems surrounding ABR across African countries are likely be distinct from other regions of the world, and therefore require regional solutions and approaches. For example, the availability of antibiotics can be patchy, and the routes of access to antibiotics are variable (including traditional healers, public and private medical practitioners and over-the- counter antibiotic access). Social, cultural and lifestyle drivers of ABR in Africa also have specific features - closer communal living in cities with variable water/sanitation, and closer animal husbandry in rural communities.  This project aims to address ABR in Africa and fill the gaps in knowledge. The research will target three main areas that comprise the problem: the bacteria that are antibiotic resistance and cause disease; the amount of antibiotics that are used to treat disease; and the behaviour of humans that governs how antibiotics are used and supplied. The three elements incorporate epidemiological, economic, cultural and societal factors that interact and contribute to the problem.   Bringing together research covering these 3 elements will provide a holistic view of ABR in East Africa. The project will establish a surveillance network across Uganda, Kenya and Tanzania that is comprised of sentinel sites that monitors and characterized the ABR bacteria that cause disease at that location, maps the use of antibiotics in the sentinel hospitals and the surrounding communities, and captures the behaviour and attitudes of humans that is responsible for their use in these setting. The project also recognises antibiotics are not exclusively used for human medicine, therefore our surveillance will also cover the use of antibiotics in veterinary medicine in the linked communities to provide a 'One Health' view. Using a multidisciplinary approach, encompassing, microbiology, genomics, epidemiology, statistics, social sciences and geography, we will seek to explore and describe the relationships between the elements, and identify the drivers of ABR.  Using this knowledge, we will identify interventions, such as public health and infection control measures and legislation changes, that can be made to control ABR at national and regional level. At the global level, the output of this project will add to the worldwide picture of ABR. This information will also be of value to global development agencies such as the WHO and FAO, to direct funding into effective interventions critical to the 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."],
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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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      "title_narrative":["Strengthening private-sector medicine systems to tackle the persistence of poor-quality medicines in Africa: a proof-of-concept study"],
      "description_narrative":["Poor-quality medicines, containing little or no active ingredient - whether through deliberate fraud, poor manufacturing practice or post-manufacture deterioration - represent a major public health threat in low/middle-income countries (LMICs): responsible for more than 200,000 under-5 deaths each year in Africa and contributing to antimicrobial drug resistance. Efforts by governments and international agencies to curb the problem through improving detection rates, tightening regulation and public education have been hampered by the economic realities of medicine supply in resource-poor, high-need contexts, but also - we suggest - by a failure to apprehend fully the complex workings of medicine supply systems, particularly beyond the public sector.   Private-sector medicine systems can be characterised as 'complex systems' involving multiple dispersed actors with no central organising authority. Recent developments in the study of complex systems have revealed how the actions of individuals can combine to have non-intuitive effects on the system as whole. This has significant implications for well-intentioned policy interventions based on 'common sense' intuition, which may have unwelcome unanticipated consequences.  Our ultimate goal is to understand - and predict - the workings of complex medicine systems in order to inform effective interventions to minimise the penetration of poor-quality products in LMICs. This will require: mapping complete medicine supply chains; understanding the motivations/behaviours of buyers, sellers and regulators; developing sophisticated computational models to simulate the system; and engaging stake-holders to co-design evidence-based interventions. This is an ambitious project which needs careful groundwork through a proof-of-concept study with the following objectives and activities:  (1) To assess fieldwork feasibility in these contexts and validate research instruments: Very few people have attempted to trace a full medicine supply chain in an under-regulated context. In order to assess feasibility, safety and ethical issues, we will map a limited number of medicine supply chains starting at retail outlets across Ghana and Tanzania and moving upwards to point of manufacture, obtaining as much relevant information as possible at each stage. Research instruments will be validated in each local context, and re-validated across contexts to ensure consistency.  (2) To develop our understandings of the structure and operation of private-sector medicine systems: Geographically weighted analysis will be employed to describe the structure/organization of supply systems (length, number of transaction points, degree/level of vertical 'collapse', etc.) and investigate spatial dependencies in the data. Thematic analysis of ethnographic data and secondary sources will be used to understand actors' decision-making and behaviour at each point.  (3) To build Agent-Based Models (ABMs) simulating medicine systems, based on empirical data: We will build a sequence of ABMs simulating medicine supply systems in Ghana and Tanzania as 'complex systems'. These models will allow us to understand, and ultimately predict, how individual behaviours might affect the system as a whole. We will develop 'user-friendly' models to use with policy-makers, highlighting potential unintended consequences of interventions.  (4) To develop and evaluate strategies for engaging relevant actors (market, regulatory, political) in the research and intervention design:  In each country, we will convene  National Stake-holder Groups (NSGs), with policy, regulatory and high-level market actors and Project Working Groups (PWGs), comprising 'on-the-ground' supply-chain actors (buyers, sellers and regulators). Through a series of collaborative workshops, we will work with 'user-friendly' models to identify potential 'bottlenecks' or problematic behavioural logics that might underpin 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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