Title: Transforming the Treatment and Prevention of Leprosy and Buruli ulcers in Low and Middle-Income Countries (LMICs)
Funder: Department of Health and Social Care

Abstract: This application is directed towards leprosy ulcers and Buruli Ulcer (BU). Preventing the problem of recurrent leprosy ulcers. We tackle the problem of recurrent ulcers caused by repeated injury and progressive anatomical changes. As with diabetes, self-care can greatly reduce the rate of recurrence of ulcers. The problem is how to make self-care happen; how to support it in communities. This is an implementation science problem in a difficult context; that of poverty and underdeveloped services. However, self-care is not expensive and we will develop and evaluate a scalable intervention. The intervention will be based on a set of principles designed to encourage local adaptation and innovation; our model is women s groups that have been used successfully to reduce perinatal death in Asia and Africa. We shall evaluate this intervention by means of a step-wedge cluster trial across three countries. Promoting healing of leprosy ulcers. Even with good prevention ulcers will still occur and they take a long time to heal. While the clinical trajectory and quality of life of people with leprosy have been studied this is not the case for people with ulcers. We will therefore establish a cohort of participants with ulcers sufficiently severe to bring them to hospital. This cohort will serve as a sampling frame for trials of treatments to overcome the problem of slow ulcer healing. We will establish an efficacy trial of a promising yet inexpensive tissue regenerative treatment in a hospital which has experience of the method. At the same time we will identify and prioritise promising treatments to promote ulcer healing through an iterative process of literature review, modelling and consensus development. We will produce protocols for evaluation of these treatments and conduct feasibility studies as appropriate. These activities will form the basis for applications for follow-on grants thereby perpetuating the academic collaborations we shall foster. Improving care for Buruli Ulcer (BU). One of our centres for leprosy care is also a referral centre for the rare condition of BU. While the clinical sequelae of BU have been studied the clinical needs of patients have not been assessed. We shall fill this gap in the literature in order to generate affordable plans to better manage this condition in context where it occurs. Likewise large BU ulcers require extensive surgery. We shall therefore identify promising new treatments to promote healing of BU ulcers and to reduce the need for surgery. As with leprosy, we will conduct feasibility studies and prepare applications for external funding. Developing a community of research practice. We will deliver the implementation of the self-care support intervention and study priorities within 18 months. At completion we will deliver the evaluation of the support intervention, the costed health needs assessment and recommendations for BU, the efficacy trial and at least three protocols for external funding. Throughout this programme we will develop a community of scientific practice, including public and communities, to advise the programme, assimilate and disseminate its outputs and to engage in the production and delivery of follow-on studies.

Lay abstract: In Low- and Middle-Income Countries (LMICs), there are diseases that tend to affect the poorest of poor people. Leprosy and Buruli ulcer (BU) are two such diseases. Antibiotics can kill the bacteria that cause disease in the first place, but that is not the end of the story. In the case of leprosy, local nerve damage leads to repeated injury and hence recurring and disfiguring ulcers, whereas Buruli ulcers are often massive by the time they are discovered and require extensive surgery. Patients (and their families) face stigma, social isolation and catastrophic costs. Our project has three main aims: To improve self-care in the community for patients who are at risk of recurring leprosy ulcers. To better understand the needs of patients with BU and the barriers to meeting those needs. To develop new and improved methods of clinical care for both leprosy and BU patients. Our study will take place in two countries that are afflicted with leprosy (Nepal and India) and a further country afflicted by both leprosy and BU (Nigeria). The first aim &ndash; supporting self-care for people in the community who are at risk of recurring leprosy ulcers &ndash; will be based on an implementation science approach where we will: Agree and share a set of principles to support self-care in the community. Build on these principles to design local interventions in collaboration with communities, patients, clinicians and policy-makers. Pilot and refine the intervention. Roll the intervention out over 20 sites in each of the three countries. Evaluate the effect of the roll-out to ensure that self-care is better supported, and that patients have better outcomes and resources are used cost-effectively. The second aim is to conduct a health needs assessment for BU to identify barriers and facilitators to meeting those needs. The third aim &ndash; developing new methods of clinical care &ndash; will translate knowledge by selecting and conducting preliminary evaluations of treatments that have a good chance of being effective and cost-effective in improving care for leprosy and BU patients. These may be: Ideas that have been tried but not proven in leprosy and BU. Treatments that are effective in other ulcer conditions and hold promise for leprosy or BU. New ideas emanating from the science base . Our project is designed to create, as an additional key output, an international Community of Practice involving researchers, community and public contributors, clinicians, and policy makers. This community will be ideally prepared and situated to build on the accomplishments of this grant and continue to collaborate, share best-practice, and innovate in care so that fewer people will be stigmatised by deformities and disabilities resulting from the two highly stigmatising diseases.

Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: INFECTION;SKIN