Despite numerous efforts by many stakeholders, Uganda still has one of the highest maternal and infant mortality in the world with the maternal and infant mortality rates being 336 deaths per 100,000 births, and 55 per 1,000 live births, respectively as of 2016. Access to quality maternal and neonatal healthcare is being stretched by lack of access to trained health professionals with doctor to patient ratios in Uganda being 25 times higher than the minimum recommended by the WHO. The biggest percentage of Uganda's population live in rural communities where access to specialised care is a major challenge due to long distances to big health facilities. Approaches such as education, advocacy, increasing access to medicine and skilled birth attendance have been used to improve outcomes. However, many mothers in Uganda and other Low and Middle Income countries are dying due to conditions such as postpartum haemorrhage, preeclampsia and malaria, whereas neonatal mortality is mainly due to conditions such as pneumonia, sepsis among others. What is very evident is the clear need for early diagnosis, better access to therapy and improved monitoring. There is therefore an urgent need for innovative, cost effective and sustainable context specific approaches to healthcare delivery, which can reduce maternal and neonatal mortality within a resource limited healthcare system. Appropriate technological innovations present an opportunity to i) deliver economic and efficient improvements in maternal and neonatal outcomes at scale, ii) replace existing technologies which are not designed for the Ugandan healthcare systems and environment, iii) reduce waste and iv) drive local economic growth. Uganda is uniquely placed in SSA in that, driven by academia and supported by the Government, it is expanding local research and technical expertise in biomedical engineering, healthcare diagnostics and technologies and healthcare innovation. We propose to capitalise on a new strategic collaboration between the University of Makerere Biomedical Engineering Unit and College of Health Sciences, and the University of Edinburgh to strengthen capacity for our proposed interdisciplinary Centre of Design, Innovation and Translational Excellence (CITE), initially focused on maternal and neonatal health. Our medium to long-term aspiration is to act as a hub to build innovation and capacity in the region, to act as a blueprint to stimulate innovations beyond maternal and child health and to expand our technological and research expertise to become the leading centre for academic excellence and innovations in biomedical engineering in sub-Saharan Africa. Our initial broad objectives are: (1) To map existing knowledge about the systems and processes for clinical evaluation of locally made Investigational Medical Devices (IMD) amongst key stakeholders in Uganda; (2) To strengthen local research capacity through training on clinical trial design for investigational medical devices and medical writing for the regulation of such devices. Training seminars, sponsorships to attend good relevant courses and exchange bench-marking visits between Makerere and Edinburgh Clinical Trials Units are some of the activities aimed at achieving this objective. The output of this objective is develop a critical mass of Ugandan researchers knowledgeable in IMD trial design, with specific expertise on trials in maternal and neonatal health; and (3) To establish a multi-disciplinary network with the expertise to develop a draft regulatory framework for Investigational Medical Devices, bespoke for Uganda.

Extending and sustaining access to safe and reliable water services remains central to improving the health and livelihoods of poor people, particularly women, in Africa. Here an estimated 350 million rural inhabitants still have no form of safe drinking water, and depend on poor quality unreliable sources for all their domestic needs. Improving access to water, and helping to achieve new international goals of universal access to safe water hinges on accelerated development of groundwater resources, usually through drilling boreholes and equipping them with handpumps. However, emphasis on new infrastructure has obscured a hidden crisis of failure, with >30% of new sources non-functional within 5-years and many more unreliable. This problem has remained stubbornly persistent over the last four decades, with little sign of sustained progress despite various interventions. Part of the reason for this continued failure is the lack of systematic investigations into the complex multifaceted reasons for failure and therefore the same mistakes are often repeated. The accumulated costs to governments, donors and above all rural people are enormous. Addressing the functionality crisis requires a step-change in understanding of what continues to go wrong. The complex issue must be approached from a truly interdisciplinary viewpoint: combining innovative natural sciences to assess the availability of local water resources and how this changes with seasons and climate; with detailed social science research of how local communities function and make decisions about managing their infrastructure; and understanding of how the engineered structures can degenerate. Underlying these reasons for source failure may be other contributory factors, such as government incentives, the role of the donor community, or long term changes in the demand for water. The overall aim of the project is to build a robust, multi-country evidence base on the causes of the unacceptably high rates of groundwater system and service failure and use this knowledge to deliver a step-change in future functionality. To achieve this aim, our research draws on a novel interdisciplinary approach using the latest thinking and techniques in both natural and social science and applies them to three African countries that have struggled for decades with service sustainability - Uganda, Ethiopia and Malawi. There are five main objectives:1.to provide a rigorous definition of functionality of water points which accounts for seasonality, quality and expectations of service; 2. to apply this new definition to Ethiopia, Uganda and Malawi to get a more realistic picture of water point functionality and therefore water coverage figures; 3. to investigate in detail 50 water points in each country by taking apart the water points and pumps, testing the local groundwater conditions, examining the renewability of groundwater and exploring in detail the local water committee; 4. we will also build on this information to forecast future rural water supply coverage by modelling the impact on water points of various potential future pathways; and 5. finally we will use all this information to develop an approach for building resilience into future rural water supply programmes and helping people decide when it is worth rehabilitating failed sources. To carry out this ground breaking research we have brought together a consortium, led by the British Geological Survey, of leading interdisciplinary UK researchers at BGS, KCL, ODI and Cambridge with groundwater academics from three highly regarded African universities (Universities of Addis Ababa, Mekerere and Malawi), and WaterAid, a leading NGO on developing rural water supply services across Africa with a history of innovation. The research has the potential to have a major impact on the delivery of reliable clean water throughout Africa, and if the results can be taken up widely break the pattern of repeated failure.

Access to healthcare remains a big challenge in Africa. The situation is particularly appalling for border resident communities as they are often not given priority by policy makers. The existence of different state territorial sovereignty, administrative frameworks with different currencies, support services, legal/regulatory systems, and languages make healthcare access for border resident populations even more complex. Unlike in the central areas; in some sparsely populated border areas, the nearest facility may be in another country. Another significant barrier lies in the economic deprivation to which the border areas are usually exposed. In this era of Universal Health Coverage, how are communities residing along national borders going to be served without any financial burden as well as ensuring their overall wellbeing? This is an overarching question we intend to contribute to. This will be done through a study conducted at five paired-cross border sites in East Africa. Specifically; four interrelated objectives are proposed; Objective 1: This will explore the existing legal-institutional contextual constraints and enablers to access to cross border healthcare services for border resident communities, by way of two main methods; 1) review of administrative and legal documents and 2) Key Informant Interviews with border officials and managers of political administrative units near the border. Objective 2: This objective will explore the health systems constraints and implications for serving border communities. Key informant interviews will be the main methods for this objective. District or county health managers and providers will provide the bulk of this category of respondents. CBOs working to improve health services will also be included in the survey as key informants. Objective 3: This objective will determine how border resident communities navigate legal-institutional and health systems constraints and enablers to health service access. Two main methods will be used a) Survey of those that successfully manage to access services across the border and b) Focus Group Discussions (FGD). For the survey, Appreciative Inquiry (AI) approach will be taken to probe the access pathways for those that have successfully navigated access to three selected services on the other side of the border. We will undertake FGDs to help to mitigate the limitation of surveying only those that successfully navigated the access barriers. The FGD participants will include potential services for cross-border services ie 1) mothers attending child immunization services, and 2) community leaders - including community health workers. Objective 4: This objective aim to identify feasible actions to advance the access and coverage agenda to services for the communities residing along state borders. This will be done through; 1) convening stakeholders to deliberate on the findings from objectives 1, 2 and 3 in order to influence policy and practice and 2) sharing the study findings with the highest regional policy platforms. At these meetings we shall engage sub national, national, and regional policy practitioners to make salient the need to plan for border resident communities. Relatedly, the findings will also be disseminated at local, regional and international conferences in addition to publishing in peer review journals. The survey is anticipated to increase understanding of healthcare access issues and the health systems implications for serving border resident communities. In turn border resident communities will benefit from improved cross border healthcare provision and greater EAC cooperation in health care delivery.

Health institutions worldwide, including the World Health Organization (WHO), have recognised that adoption and innovative use of information from electronic medical records will be necessary to provide equitable care to the growing population of the world. Uganda is committed to meeting this goal, however, there are challenges to developing and implementing electronic health record data capture and analysis systems, especially as implementation of these systems have mostly occurred in high-income countries where challenges are different. In this project, we will assess whether or not Uganda is ready to implement an electronic health record data capture system at the point of care that can centrally process information through statistical analysis and provide important information to care providers and public health practitioners to support healthcare delivery. This assessment involves collecting information from key stakeholders about barriers, facilitators, costs and other 'readiness' factors, such as acceptability and training of the healthcare professionals who will enter data into the system. We will map these measures to known models of electronic health record adoption readiness and technology adoption success. We will also assess the opinions of the community on how their health information should be handled and used. Additionally, we will look at the technology components of this system that may already exists and determine the costs to provide all necessary components. Finally, we conduct analyses to determine how long it will take to see benefits in terms of cost savings in healthcare provision. The Ministry of Health in Uganda has recommended a 'stepped' approach to adopting electronic health records, we will therefore focus on areas of greatest concern to the Ministry of Health. While Uganda has a number of important health concerns, such as child and maternal health and cancer, we will focus predominantly on malaria and HIV, and also look at scope for other infections. The reason for this choice is that these infections are still some of the leading health problems in Uganda, and they are treatable. This means that if successful implementation of electronic health record data capture occurred, combined with faster, more efficient and effective treatment due to processing those data and providing key information, such as who to target for testing and treatment, we could reduce costs to the health system and increase human health. The findings of the study will be shared with the scientific community and provided to the Uganda Ministry of Health as a report. The Ministry of Health plans to use this report as a guide to developing their electronic medical record and information analysis platform.

Cryptococcal meningitis (CM) is a major causative agent of fungal meningitis worldwide. In sub-Saharan Africa, cryptococcal meningitis is the most common cause of meningitis in adults and causes 20-25% of AIDS-related mortality. The excessive early mortality from cryptococcosis is in large part due to the high cost, toxicity, and relatively limited repertoire of available anti-fungals, which have changed little in the last 30 years. For these reasons, the identification of new anti-fungals effective for the treatment of fungal meningitis must be a high priority. One problem with many current anti-fungal drugs is that they penetrate poorly into the brain. This is a particularly difficult problem in treating fungal meningitis, which is an infection around the brain. New research suggests that sertraline, one of the most widely prescribed antidepressants in the world, has anti-fungal activity against Cryptococcus. The findings are the result of investigations testing sertraline against Cryptococcus neoformans in culture, in a mouse model of infection, and in studies of it's mechanism of action which appear to be inhibiting protein synthesis in the Cryptococcus yeast. Sertraline is known to be well-tolerated and is effective as an antidepressant. Preliminary investigations of sertraline in a mouse model of systemic cryptococcal infection revealed that it combats infection with efficacy similar to fluconazole, an oral anti-fungal drug used commonly for fungal disease since 1990. Most importantly, the combination of sertraline and fluconazole was found to work better than either drug alone. Sertraline is concentrated in the brain (average of 22-fold over blood levels), and thus may be an ideal oral medicine to add to standard therapy for cryptococcal meningitis. Despite these promising initial studies, no studies have been conducted in actual humans. This study seeks to help answer these questions. The research team, based in Uganda, plans to determine whether the addition of sertraline to standard therapy for CM will result in more rapid clearance of the fungal infection. An This project will have two phases. An initial pharmacokinetic dose finding and safety study was conducted Aug 2013-Feb 2014 which has informed the sertraline dosing choices, confirmed the general tolerability, and provided preliminary data that the rate of clearance of yeasts from the cerebrospinal fluid (termed early fungicidal activity) is approximately 25% faster over the first two weeks than current standard therapy. This proposal is for support of a multisite, Phase III study to determine whether sertraline improves survival in comparison to placebo. All research participants will receive standard anti-fungal therapy of amphotericin + fluconazole as induction therapy. The implications of this research are clear. Since strong safety data already exists, investigation into the use of sertraline as anti-fungal is greatly accelerated. If sertraline proves to be effective in treatment of Cryptococcus in humans, it would be immediately available for use, essentially creating a shortcut from bench to bedside. This would result in huge cost savings compared to bringing an entirely new drug to the market. Sertraline could have the potential to revolutionize cryptococcal care in Sub-Saharan Africa as it is an existing low cost, generic medicine made by >=25 manufacturers worldwide.