Title: NIHR Global Health Research Group on the Application of Genomics and Modelling to the Control of Virus Pathogens (GeMVi) in East Africa at the University of Warwick.
Funder: Department of Health and Social Care

Abstract: a) Building on strategic objectives of the host institution. The proposed GHRG will be led from the Zeeman Institute (ZI) for Systems Biology & Infectious Disease Epidemiology Research (SBIDER) and School of Life Sciences at the University of Warwick (UoW), but will be driven by a central partnership between UoW and the KEMRI-Wellcome Trust Research Programme (KWTRP) in Kenya. KWTRP and ZI are both leading groups in two key approaches in modern epidemiology, namely mathematical modelling and pathogen genomics. Separately they can act as regional hubs providing training to the next generation of epidemiologists; together they can generate new understanding and methodologies by combining these two fields of expertise. UoW’s organisational values are Excellence of Research, Making a Difference and having a Global Perspective, which mesh with the aims of our GHRG. UoW is a world-leader in key areas of impactful research, epitomised by its targeting of ‘Science & Technology for Health’, International Development’ and ‘Sustainable Cities’ as Global Research Priorities. The university also has a strong ethos of outreach to low-income settings, with ‘Warwick in Africa’ being a flag-ship initiative for campus-wide involvement in African education programmes. UoW is committed to international collaborations and views modern predictive epidemiology as a key strength through which this can be realised. SBIDER is renowned for its development of quantitative methods in infectious disease epidemiology and areas of systems biology. It has a strong focus on science for policy, with expertise in cost effectiveness modelling for vaccination, control of livestock diseases, and the elimination of neglected tropical diseases (NTDs). UoW has long-standing links to KWTRP, primarily through James Nokes, but also involving multiple members of staff being involved in research projects, co-supervising Kenyan PhD students and academic visits to the facility. This collaboration will be widened and strengthened by this award. b) Why the institution is well-placed to be making this application UoW is renowned for its research in Maths & Statistics (3rd in REF 2014) and Computer Science (2nd in REF); and has a reputation for bringing these quantitative methods to bear on problems in epidemiology, systems biology and bioinformatics, through detailed collaborations with applied researchers in the flourishing Warwick Medical School and School of Life Sciences with their expertise in health sciences, microbiology and infection. UoW is also renowned for its high-quality training in areas of applied quantitative research, exemplified by: Maths for Real World Systems Doctoral Training Centre (DTC) (Maths), OxWaSP DTC (Statistics), MRC Doctoral Training Partnership in Interdisciplinary Biomedical Research (Warwick Medical School), and the Midlands Integrative Biosciences Training Partnership (Life Sciences). SBIDER has world-leading expertise in the development of predictive models for public-health planning and policy. This builds on the superb international reputation of the mathematics, statistics and computer science departments for high-quality quantitative research, and emphasises the critical link between real-world data, clinical experience and prediction. SBIDER also has strong links across campus to Life Sciences, Medicine, Social Sciences and Policy. It has 17 academic staff with interests in public-health, over 20 Post-Doctoral Research Associates and a similar number of PhD students. Two pieces of work highlight our approach and strengths: we provide the UK Department of Health with second-opinion modelling and economic evaluation for vaccination; while for the past 4 years we have hosted the NTD modelling consortium, predicting the impacts of disease control in LMIC. (c ) Links to existing partnerships, complementary investment, and strengthening and sustaining capacity and capability The central collaborative axis of the project is the Warwick/KWTRP relationship. Prof Nokes, has been based at KWTRP for 16 years whilst being appointed at the UoW School of Life sciences and is a member of SBIDER. The research goals of this project are complemented by, and will strengthen, the long term research at KWTRP on surveillance, molecular diagnostic and sequencing methods for respiratory viruses. Additional to the Warwick/KWTRP axis are a cluster of existing relationships between KWTRP and East African research institution and university partners. A central strategy of this project is to leverage the Regional success of the DELTAS Africa scheme in finding, and further developing, the next generation of scientific leaders in East Africa. Specifically, GeMVi will work through three DELTAS programmes (11), namely, IDeAL (lead institute is KWTRP), SANTHE (KWTRP is a Partner Institute) and MUII+ which is a collaboration between Uganda Virus Research Institute (UVRI) and Makerere University, in Uganda. GeMVi will add value to these consortia by extending the opportunity for developing research capacity and increasing the translational focus through involvement of public health stakeholders. (d) Involving partners, users and stakeholders We will engage with our partners and country stakeholders in East Africa to draw up a list of priority research areas and themes. These will focus investigations conducted by our Research Fellows (RFs). This engagement will be facilitated by established links with health research institutions in the region, interactions between all partners and country level stakeholders (eg Ministries of Health, WHO, Medical/Veterinary Research Institutes) and through representation on our GHRG Advisory Committee (see appended organisation schema). The geographic focus of this project is Kenya, Uganda and Tanzania (although we would not discourage interest from other countries in the region); which are all classified as least developed or low-income countries. We will hold two workshops in which the GHRC’s and its Partners’ research will be presented. Members of the Universities to which the RFs are affiliated will attend, and representatives of Health Authorities and Institutes, and the Advisory Committee will be invited. We will also participate in one or more of the research symposia that run in East Africa (e.g. Infectious Disease Conference of the ID Society of Kenya; Medical and Veterinary Virus Research (MVVR) Symposium, organised by KWTRP; and African Society for Bioinformatic and Computational Biology conference).

Lay abstract: Sub-Saharan Africa bears the main burden of mortality from infectious disease(1), which impacts on economies, trapping people in poverty. The UN Strategic Development Goal 3 ‘Good Health and Well-being’ (2) is unlikely to be met without confronting this problem. Endemic and emerging viral diseases are major contributors. In East Africa the toll from human viruses is both large and diverse, and include, epidemics of influenza; drug resistant HIV, measles despite national vaccination; recurrent arbovirus and zoonotic introductions (eg dengue and Rift Valley Fever Virus), and emergent viruses such as Zika and Ebola. There is clear need for specialised training and coordination of resources to generate high quality evidence that provides accurate and timely assessment of disease risk, spread and optimal strategies for control(3). The goal of the Warwick-East Africa GHRG ‘GeMVi’ is to improve capacity for response to endemic, epidemic and pandemic viral disease in East Africa. To do this GeMVi will focus on the application of whole genome sequence (WGS) data (4-7) and predictive models (8-10) to support intervention decisions. It will extend and enhance the collaboration between University of Warwick and KEMRI Wellcome Trust Research Programme, and create a network of research centres in Kenya, Uganda and Tanzania. Technical advances in the integration of genome sequence data and models of infectious disease transmission will be made. GeMVi will develop, train and support future East African leaders in virus genomics and mathematical epidemiology. These training and capacity developments will result in improved response and evaluation capability that will support targeted public health responses to threats posed by viral infections. Specifically GeMVi objectives are to 1. Create a sustainable collaborative network of institutes (UK and East Africa) that collectively support applied virus epidemiological research and provide an evidence base for decision making by public health authorities in East Africa. 2. Provide training and research support for a cohort of 20 quantitative East African scientists to develop advanced skills in viral genomics and predictive modelling. This will enable them to address locally defined problems and input into country-specific recommendations. 3. Establish and transfer genome sequencing methods (eg compact real-time Nanopore technology) with associated analysis steps (or pipelines) for virus Next Generation Sequence (NGS) data, and construct mathematical models to predict the impact of different intervention options. Outputs will be open source resources for combining sequence and epidemiological data analysis with transmission dynamic modelling. 4. Develop the Zeeman Institute at the University of Warwick as a centre of expertise for integrated mathematical and genomic epidemiology, with meaningful ties to East African Institutes. 5. Establish an East African Alliance for Virus Prevention and Control Preparedness (VPCP) with the aim of coordinating research-evidenced responses to public health needs. The work will lead to measurable benefit for the East African public through: (a) increased and coordinated scientific capacity to respond to and control diseases posing major public health risks (b) generating research outputs with a bearing on public health decision making (c) establishing a clear link between virus pathogen evidence-based research and public health decision makers in East Africa.

Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: INFECTION