Title: NIHR Global Health Research Unit on Tackling Infections to Benefit Africa, The University of Edinburgh
Funder: Department of Health and Social Care

Abstract: UoE is a world class university with strengths in, and a strategic commitment to, infectious diseases and global health, as well as strong links with Africa (see Letter of Endorsement). TIBA is a unique initiative across Colleges, research centres and disciplines within UoE, with 8 named applicants representing over 200 PIs in our infectious diseases and global health communities (see Letters of Support from Edinburgh Infectious Diseases, Global Health Academy, Centre for Global Health Research). Within Edinburgh, TIBA combines research groups with impressive track records in delivering health improvements in Africa with major initiatives offering world class facilities and technical expertise (see Letters of Support from Edinburgh Genomics, SynthSys, Innogen). UoE has over £100M of active grants for infectious disease and global health research, linked to substantial infrastructure investment. These resources offer considerable added value to the work of TIBA and point to the long term sustainability of this initiative. Coupled with the tremendous strengths of our African partners (see Team Expertise), we believe we are uniquely placed to realise TIBA’s ambitions. TIBA’s aims will be delivered by collaborative and coordinated activities organised as 6 work packages (see Supporting Diagrams): WP1 Rapid Impact projects; WP2 Making a Difference projects; WP3 Toolkit projects; WP4 Technology transfer and training; WP5 Dissemination for action; WP6 Responding to health emergencies. WP1 (Years 1-2) TIBA will support 9 Rapid Impact (RI) projects, one proposed by each African partner. These are designed to capture the diverse challenges of health care systems in Africa and will both inform the development of our Making a Difference projects and provide data for our Toolkit projects. Each RI project will address a current knowledge gap which is resulting in either non-deployment of diagnostics or interventions or a lack of operational knowledge to improve the health of affected populations. The projects are: -Optimisation of WHO guidelines for the frequency and timing of treatment of pre-school children with a new formulation of paediatric praziquantel for control of schistosomiasis in the community (Zimbabwe) [1]. -Implement oxygen interventions for childhood pneumonia and assess outcomes using the IN-DEPTH surveillance system (Kenya) [2]. -Field trials of a prototype £10K lab-in-a-box for rapid diagnostics for a broad range of pathogens (Ghana). -Enhance a web interface platform for information-sharing during disease outbreaks to increase its visibility and utility to health agencies in Africa, including mobile phone access (Botswana) [3]. -Revise international criteria for the diagnosis of drug/immunization-related auto-immunity and allergy to be specific to African rather than western populations, cognizant of local infection patterns (South Africa) [4]. -Investigate the impact of mixed Plasmodium species infections as an impediment to malaria elimination programmes and optimization of drug regimens (Sudan) [5]. -Study the impact of Global Health Security Agenda efforts to achieve the International Health Regulation core capacities on progress towards universal health coverage in partner countries (Tanzania) [6]. -Case study of best policy and practice involving a ‘One Health’ approach to trypanosomiasis control (Uganda) [7]. -Evaluate recently introduced drone delivery systems for medicines in remote areas (Rwanda) [8]. WP2 (Years 2-3) We will commission 5 Making a Difference projects using the following criteria: -Demonstrate relevance to national health needs; -Clear pathway to impact, i.e. policy change, uptake by end users; -Propose indicators for measuring impact on poorest people; -Involve 2 or more Africa partner countries; -Fit with TIBA aims and objectives. -Provide opportunities to progress the WP3 Toolkit agenda (see below). Candidate projects for WP2 include: -Investigation of better ways to access pre-school children for schistosomiasis control in the context of the different child health primary care systems in place in partner countries [1]. Results will inform the rolling out of schistosomiasis treatment by the WHO to >50M pre-school African children by 2021. - Development of novel diagnostics and surveillance systems to detect symptomatic and asymptomatic cases of the gambiense form of human sleeping sickness (gHAT) among South Sudanese refugee populations in northern Uganda. Results will help target measures to protect 11M people at risk of sleeping sickness and will support WHO’s efforts to eliminate gHAT by 2030 [9]. - Pneumonia affects 35M African children annually but poor validity of current case management compromises effective treatment [10]. Embedded in IN-DEPTH, we will assess new technologies including thermal imaging devices linked to mobile phones and develop and field test new algorithms to improve diagnosis. - Identify novel candidates for anti-malaria vaccines using monoclonal antibodies identified in longitudinal biobanked samples from naturally exposed individuals [11]. This approach diversifies efforts to develop malaria vaccines which, if successful, could help protect >100M African children. The technology is transferable to other infections. - Localised disease hotspots are compromising the WHO programme to eliminate lymphatic filariasis (LF). We will trial intensive surveillance, vector control and a DOTS approach to treatment in hotspots in coastal Tanzania to help protect 36M people at risk and assess potential for accelerating LF elimination in other endemic countries [12]. WP3 (Years 3-4) :4 Toolkit projects are a unifying framework for extracting lessons learned from all TIBA activities for collation and dissemination, covering: 1) Strengthening health systems. TIBA will emphasize a systematic, evidence-based approach designed to bring about significant improvements in: i) health delivery systems in African countries; ii) patient and population health uptake and outcomes, particularly among the poor; iii) efficiency and effectiveness of systems and processes of care. We will develop context-specific strategies for health communication and changing end-user behaviour. 2) Innovation-to-application value chains. We will use the WHO’s 6 health systems building blocks [13] (leadership, financing, workforce, technologies, information and delivery) as an analytical lens to better understand how a responsive, context-specific innovation-to-application pipeline can be constructed [14]. 3) Information exchange and data sharing. Unprecedented efforts are underway in Africa to electronically capture and exchange health information to improve health care and population health, and reduce costs [3]. TIBA will work on both technical and governance issues around eHealth. 4) Best practice for capacity building and training. TIBA will share experiences and formally review capacity building initiatives within the partnership. WP4 (Years 1-4) : Capacity building through technology transfer, study visits and workshops, together with Masters, doctoral and postdoctoral training will be embedded in all of TIBA’s activities (see Research Capacity). Individual projects will complement the work taking place in WP1-3. WP5 (Years 1-4) : Communication with end users will be embedded in all of TIBA’s activities from the outset (see Collaborations and Partnerships). WP6 (Years 1-4) : Our responsive research capability will concentrate on 3 areas in which UoE and partners have particular strengths: field diagnostics, data sharing, and real-time genomic analysis [15]. UoE is developing portable diagnostic kits for viral, bacterial and parasite infections employing biomarkers, electrochemical and bio-sensors, or sequencing technologies. UoE and several Africa partners (Kenya, Botswana, South Africa) are taking an eHealth approach to improving outbreak surveillance by optimising technologies (e.g. smart phones), surveillance system design and data communication capabilities. UoE has played a leading role in data sharing activities relating to Ebola and avian influenza epidemics, including building global partnerships and setting up generic data sharing platforms [15,16]. We will deploy this expertise in future outbreaks. TIBA has a substantial bioinformatics capacity (Edinburgh Genomics, Kwazulu-Natal) and phylo-analytics capability, allowing us to generate policy-relevant outputs in real time (as UoE is currently doing for the ongoing avian influenza epidemic across Europe). TIBA provides an opportunity to integrate these mutually supportive activities and make a significant contribution to the coordinated management of future outbreaks. We will liaise closely with the newly established Africa CDC. WP3 will deliver the some of the tools required by the WHO R&D blueprint for action to prevent epidemics [17]. Sustainability. From Year 2, UoE will hold sustainability planning meetings of the TIBA Directorate, Edinburgh Research and Innovation, Research Support, and Development and Alumni to support the directorate in securing future avenues of funding for the project. Already, we have begun discussions with the Wellcome Trust (Head of Infection) about a WT Centre bid in 2021, noting that TIBA is closely aligned with WT strategies for supporting high impact science in Africa. We will seek technology development awards (e.g. Ross Fund) and industry support (see Additional Information) for our work on diagnostic tool kits, drugs and vaccines. We will also target African funding sources, noting that Agenda 2063 calls for the establishment of an African Science, Technology & Innovation fund to increase R&D spend [18,19]. We will engage with African philanthropists (e.g. contributors to the END fund for NTD control). We anticipate that a successful TIBA would rapidly expand to include other African countries

Lay abstract: TIBA's vision is to harness the expertise and technical capability in biomedical and social sciences at the University of Edinburgh (UoE) and our African partners to reduce the burden and threat of infectious diseases in Africa by informing and influencing health policy and strengthening health systems. Africa bears a disproportionate burden of infectious diseases, with a major impact on childhood mortality rates. UN Sustainable Development Goal 3 (Good Health and Well-being) will not be achieved without tackling infectious diseases in Africa. Outbreaks such as Ebola can overload overburdened health systems already facing multiple challenges. We believe that access to the best science and technology will help Africa respond to African problems. To help achieve this, we have created a new partnership: Tackling Infections to Benefit Africa (TIBA). The Swahili word ‘tiba’ means to cure an infection. TIBA is a collaboration between UoE and leading African scientists in Botswana, Ghana, Kenya, Rwanda, South Africa, Sudan, Tanzania, Uganda and Zimbabwe. TIBA is addressing two needs: to manage infectious diseases in the wider context of African health systems; and to shift the centre of gravity of health research for Africa to institutions in Africa. We are conducting an Africa-led, wide-ranging, multi-disciplinary research programme that explores and draws lessons from the ways that different African health systems tackle a range of infectious diseases. Uniquely, TIBA is working on all aspects of infectious diseases management – from basic research to uptake by local communities – in a single, unified framework. This meets an often articulated but rarely addressed need to view infectious disease management not in isolation but in the context of local health systems and wide societal issues. TIBA is also contributing to the strategic goal of improving the health research ecosystem in Africa, providing a rare opportunity for different countries to work together in a common framework. TIBA has four specific aims: - Improve the diagnosis and surveillance of infectious diseases in resource-poor settings. - Improve the deployment of existing drug treatments and enhance local capacity to develop new ones. - Improve the deployment of existing vaccines and enhance local capacity to develop new ones. - Improve the management of both endemic and emerging infections by: i) strengthening health systems, with special attention to ethics and governance; ii) improving policy development and implementation (e.g. drug procurement, local licensing, regulatory harmonization); iii) enhancing capacity to respond to infectious diseases emergencies, while protecting capacity to manage endemic diseases concurrently. TIBA is focussing on a set of largely neglected diseases – schistosomiasis, malaria, respiratory infections, trypanosomiasis and lymphatic filariasis – all important in their own right but each one also providing opportunities to explore the ways in which health systems operate and respond to changes in policy, new scientific knowledge, or technological innovation. TIBA's activities are structured as a set of work packages covering project delivery, training and capacity building, dissemination and emergency response.

Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: INFECTION