Title: NIHR Global Health Research Unit on Neglected Tropical Diseases, BSMS
Funder: Department of Health and Social Care

Abstract: a) As Europe’s top University for Development Studies, second only to Harvard globally (2), the University of Sussex (UoS) is an influential academic institution with a strong strategic plan that puts innovative critical thinking and its hallmark interdisciplinary approach at the heart of its global health (GH) research. UoS has pump-primed the development of two GH research centres (the Wellcome Trust Brighton and Sussex Centre for Global Health Research at BSMS, referred to in the rest of this bid as ‘our Centre’, and the Centre for Global Health Policy, CGHP). It has provided funds to our Centre to establish a multidisciplinary International Antimicrobial Resistance Network and to extend our work on podoconiosis into Latin America. £3million has been allocated to the Sussex Sustainability Research Programme linking UoS and the Institute of Development Studies (IDS). Both BSMS and UoS are ambitious to further develop GH research and the work described in this proposal will build on our achievements to date. We will develop new projects in under-researched but debilitating conditions that affect the lives of millions, causing stigma and poor mental health that worsen existing poverty. b) UoS is well-placed to host a NIHR Global Health Research Unit (GHRU). Since opening in 2003 the Medical School has developed a thriving programme of world-class GH research that is truly interdisciplinary in its approach, working in partnership with low and middle income country (LMIC) institutions. Existing BSMS academic posts within the Department of GH and Infection, where the GHRU will be based, include 3 professors, 5 senior lecturers, and 2 lecturers. c) BSMS GH researchers have a track record of world-class, equitable and enduring research collaboration with institutions in Development Assistance Committee (DAC)-listed countries. A Wellcome Trust strategic award supports our Centre, a partnership between BSMS, the Armauer Hansen Research Institute in Ethiopia, the University of Khartoum in Sudan and the University of Buea in Cameroon. Our Centre also partners with CGHP (UoS), the Nowgen Centre (public engagement, Manchester) and the Centre for Research on Genomics and Global Health at National Institutes of Health (NIH, USA). With a strong focus on capacity building for independent research, we are committed to creating supportive environments that empower scientists to contribute to a wider African research enterprise. This application will allow us to build on these mature partnerships whilst researching major under-researched neglected diseases. It will also enable us to deliver social science and health economics research, develop community-based interventions, strengthen health system responses and inform policy, translating our research into tangible benefits for our stakeholders. d) Our vision is to undertake world-class interdisciplinary research to provide an evidence base for interventions targeting the neglected tropical disease (NTD) epidemic with approaches that ‘leave no one behind’ (3). Our Centre acts as an international, interdisciplinary research hub for podoconiosis, a disabling geochemical lymphoedema considered an ‘other neglected tropical condition’ by WHO that is estimated to affect over 4 million people in Africa. Over the last ten years we have researched the epidemiology, mineralogy, genetics, bioethics, economics, clinical management and social impact of podoconiosis (4-11). We will apply our experience in translational research on podoconiosis to other neglected conditions - mycetoma and scabies - that significantly affect the communities we already work with, and extend our methodology to include expertise in health economics and service development. WHO adopted mycetoma (a chronic destructive infection that spreads from subcutaneous tissues to involve the deep structures and bones) as a NTD in 2016 (13). The 69th World Health Assembly specifically called for research “to develop new tools to diagnose, treat and prevent mycetoma”. We will focus on tools and strategies for prevention, using our experience developing and testing behavioural interventions to prevent podoconiosis (14,15). Like podoconiosis, scabies (a skin infestation that causes profound itching and can lead to serious bacterial infections) is considered an ‘other neglected tropical condition’ by WHO. Scabies is estimated to infest 130 million people at any given time and disproportionately affects children and vulnerable people (16). Like mycetoma and podoconiosis, scabies has received little investment in laboratory, epidemiological or operational research. A recent outbreak in Ethiopia driven by drought, overcrowding, malnutrition and poor access to sanitation, led the Ministry of Health (MoH) to highlight scabies as a high research priority that we have the expertise to respond to. Our long term aims are to work with our partners to: • improve our ability to diagnose, prevent and treat podoconiosis • develop tools to prevent mycetoma, given the lack of effective treatment • improve the ability of LMICs to respond to scabies outbreaks • provide a sustainable long term framework for research across a range of other NTDs including leprosy, lymphatic filariasis, Buruli ulcer and yaws. Our specific objectives are to: • integrate and scale up community-level care for podoconiosis with that of other foot-related diseases in Ethiopia • develop tools with which to diagnose podoconiosis and measure lymphoedema • improve understanding of the pathogenesis of podoconiosis • identify endemic plant extracts suitable for lymphoedema limb care • ascertain environmental risk factors for mycetoma • develop a community-level prevention programme for mycetoma • refine the public health response to LMIC scabies outbreaks. We have developed seven work packages (WPs) to achieve these goals (see Gantt chart) and our short, medium and longer-term aims are described below: WP1. Integration and scale up of community-based holistic care package for people with lymphoedema in Ethiopia. Year (Y) 1 finalise core package of care; Y2 pilot this in a single district: situational analysis, asset mapping, theory of change workshops; Y3&4 regional scale up and evaluation; economic analysis. WP2. Lymphoedema volume measurement and podoconiosis diagnostic tool. Y1 validate LymphaTech (17) device among patients with lymphoedema. Y1-3 design, construct and field test portable bioimpedance spectroscopy system. Y4 develop commercial partnership. WP3. Understand the pathogenesis of podoconiosis. Y1-2 peripheral blood cytometry, transcriptional profiling, use new techniques to do secondary analysis of existing genetic data adding value to previous studies; Y3-4 further characterise the molecular basis of genetic association (6) using results from Y1-2 towards new treatments and diagnostics development. WP4. Identify endemic plant extracts for lymphoedema care in Ethiopia. Y1-3 collect and identify plants, characterise extracts. Y4 design protocols for pragmatic trials of external use. WP5. Epidemiological mapping of mycetoma in Sudan. Y1-2 algorithm development, nationwide fieldwork. Y2-4 geospatial modelling, burden assessments, economic analysis. WP6. Develop community-based mycetoma prevention programme. Y1 qualitative investigation of understandings of disease, aetiology and prevention. Y2 development of prevention package. Y3-4 Community-based feasibility studies to trial prevention package. WP7. Refine public health response to scabies outbreaks in Ethiopia. Y1-2 physical and psychosocial impact assessment of ivermectin mass drug administration. Y3-4 development and testing of outbreak response. Our team collectively has proven experience in the methodologies and techniques required to successfully deliver the WPs (e.g. refs 4-6,8,9,15,18-20). e) WPs have been prioritised after discussion with our academic collaborators and other users of research in Ethiopia and Sudan. These include the Disease Prevention & Control Directorate of the MoH, Ethiopia, the Mycetoma Research Centre, Khartoum and patient associations. These groups will continue to be closely involved as the WPs are developed into full protocols and delivered. f) N/A g) Unit resources will be available to respond flexibly to emerging GH research requirements through the availability of staff time, expertise and UoS facilities. We have expertise in rapid ethics appraisal (REA) at the start of research projects to guide the consent process ensuring research in time-pressured situations remains ethically robust across a range of studies (21-24). The social science and health economics expertise included in this bid will broaden our responsive capacity. h) Please see UoS letter of endorsement for its commitment to sustain the GHRU when NIHR funding ends (salaries, infrastructure, studentships). The proposed Director and co-lead have a track record of sustained partnerships with LMIC collaborators. They are built on trust, equity and respect and have developed despite fluctuating levels of funding. Our Centre has a reputation for building research capacity relevant to LMIC research agendas, and ensures researcher sustainability through training that equips researchers for future independence. We will also work to secure external funding that extends beyond 2021. A hallmark of our Centre’s translational approach has been its success in winning support to implement research findings. In 2014, the Centre’s research on podoconiosis distribution, prevention and treatment underpinned an application to the UK National Lottery to support prevention and treatment activities in the three most affected regions of Ethiopia. The £2m ‘Preventing Podo Project’, a partnership between UoS, the National Podoconiosis Action Network and the MoH in Ethiopia, has enabled relationships with these implementing groups to be maintained (25).

Lay abstract: Our NIHR Global Health Research Unit grant was awarded in June 2017 and the funding finishes in March 2021. Our work will focus on research into three conditions: podoconiosis, mycetoma and scabies. Together, they affect millions of vulnerable people in poor communities in low-income countries such as Ethiopia and Sudan. • Podoconiosis is a progressive form of leg swelling often seen in barefoot farmers • Mycetoma is a slow-growing, destructive infection of the skin and underlying tissues • Scabies is a profoundly irritating infectious skin condition caused by tiny mites burrowing into the skin and occurs in outbreaks in vulnerable communities They are all painful, disabling and reduce mobility which has a severe negative impact on productivity at household, community and national levels. They are associated with high levels of stigma which creates social isolation, reduces opportunities for education and increases the risk of poor mental health. Knowledge of these neglected diseases within health care systems is often inadequate. Diagnosis and treatment options are limited and the cost of accessing health care to ease symptoms can be prohibitively expensive. Our long term aims are to work with our partners to: • Improve our ability to diagnose, prevent and treat podoconiosis • Develop tools to prevent mycetoma, given the lack of effective treatment • Improve the ability of low and middle income countries (LMICs) to respond to scabies outbreaks • Provide a sustainable long term framework for research across a range of other neglected tropical diseases (NTDs) including leprosy, lymphatic filariasis, Buruli ulcer and yaws • Build capacity in both countries to carry out similar research after the programme lifecycle has ended Our specific objectives are to: • Integrate and scale up community-level care for podoconiosis with that of other foot-related diseases in Ethiopia • Develop tools with which to diagnose podoconiosis and measure lymphoedema • Improve understanding of the pathogenesis of podoconiosis • Identify endemic plant extracts suitable for lymphoedema limb care • Ascertain environmental risk factors for mycetoma • Develop a community-level prevention programme for mycetoma • Refine the public health response to LMIC scabies outbreaks To achieve these, we have designed seven work packages: • WP1 – integration and scale up of care package for people with lymphoedema (Podoconiosis) • WP2 – Volume measurement and diagnostic device (Podoconiosis) • WP3 – Immuno-pathogenesis studies (Podoconiosis) • WP4 - Identification of endemic plant extracts for limb care (Podoconiosis) • WP5 – Epidemiological mapping of mycetoma in Sudan (Mycetoma) • WP6 – Development of a community prevention programme – (Mycetoma) • WP7 – Impact evaluation – mass drug administration (MDA) with ivermectin (IVM) for scabies Central to our approach is to train and empower future researchers from Ethiopia and Sudan. Our goals will be met using methods that build capacity to do similar research in both countries that will lead to the elimination of diseases and improve the health and wealth of individuals living in Ethiopia and Sudan.

Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM;SKIN