Title: NIHR Global Health Research Group on Improving the Management of Acute Brain Infections at University of Liverpool
Funder: Department of Health and Social Care

Abstract: A) UNIVERSITY STRATEGIC OBJECTIVES Infection as one of three University-wide research themes at the University of Liverpool (UoL). UoL is recognised internationally as a world leader on infection research in lower and middle income countries (LMICs), which was consolidated with £70M investment in its Institute of Infection and Global Health in 2010. The University’s Strategic Plan 2016-25 acknowledges infection as its strongest area of research, committing to further major investment. This includes UoL staff permanently embedded within partner institutions in LMICs (including Malawi), and investment in postgraduate research opportunities for students from LMICs, through dual/joint PhD programmes (including in Malawi and India). Within the University’s infection portfolio, the research on brain infections is one of its strongest areas, and has attracted considerable institutional support, including key recent staff appointments to develop this area. B) UNIVERSITY STAFFING AND SUPPORT UoL has 111 members of academic staff (41 professors) working in infection with £110.8M of research funding raised over the last 5 years. Underscoring UoL’s commitment to the area of global infection research, 21 new senior appointments have been made in the past 5 years, including 5 UoL staff based permanently in overseas partner institutions, with a similar number of junior appointments. The University’s brain infections research portfolio has been strengthened over the last 12 months with key appointments, including three Senior Clinical Lecturers working on brain infections (all coapplicants on this grant). UoL will provide 100% funding for the Clinical Research Fellow for this GHRG, provide support staff, and underwrite the time of Research Leaders, for whom only a nominal charge is made. Liverpool’s research on neurological infections is led by the Liverpool Brain Infections Group, which aims to reduce the global burden of neurological infections through: - Improved disease recognition and diagnosis - Greater understanding of the disease mechanisms - Better patient management and the development of new treatments - Work with Governments and the World Health Organisation to improve disease control. Headed by Solomon, the group currently comprises 33 members (Academic Staff, Post-Doctoral Research Assistants, Fellows, PhD students), working on brain infections in the UK, Africa, Asia and Latin America. However, these have all been bilateral relationships with different countries. This NIHR GHRG will for the first time pull countries together into a single programme of work, which will allow comparative studies. In addition, by combining with Warwick’s Centre for Applied Health Research and Delivery, it develops a programme of applied research introducing complex interventions to improve patient management. The Liverpool group’s work is supported by £25M of grant income from NIHR, Wellcome Trust, MRC, European Union, and other funders. Many former group members have returned to their own countries, where they now hold academic positions, including one who is a LMIC co-applicants on this grant. FACILITIES: The GHRG will benefit from: - UoL’s £90M capital investment plan which has created a world class environment for global health research, including the new Ronald Ross Building (£40M; 5,000m2 of state-of-the-art facilities, where the Liverpool Brain Infections Group is based) - LSTM’s £28M Centre for Tropical & Infectious Diseases, and £7M Wolfson Building, both support translational and applied research - UoW’s Centre for Applied Health Research and Delivery which aims to develop practical solutions to health needs, and transform health systems in resource limited nations; supported by £12M of external grant funding. C) INSTITUTIONAL PARTNERSHIPS The application builds on UoL’s strong relationship with UK partners, Liverpool School of Tropical Medicine (LSTM). UoL and LSTM co-host the: - Wellcome Trust (WT) Centre for Global Health Research (£700K, since 1997; supporting 78 successful WT Fellowship applications, total value £27M - Malawi-Liverpool-Wellcome Trust (MLW) Major Overseas Programme (est. 1995, grant income £60M since 2012) - new Centre for Excellence in Infectious Disease Research, which provides an academic industrial interface to speed translational research, e.g. with Unilever. The application develops a new partnership between the Liverpool Brain Infections Group and the Centre for Applied Health Research and Delivery (CAHRD), University of Warwick, to help ensure the maximum impact in terms of policy and implementation, of the research developed. Our GHRG includes world-leading overseas partners with whom UoL already has strong institutional links, either because UoL staff are permanently based there (Malawi) or because of innovative dual/joint PhD programmes (Malawi and India): - The College of Medicine (CoM), Malawi, which hosts the MLW Unit - The National Institute for Mental Health & Neuroscience (NIMHANS), Bangalore, India In addition, this GHRG will strengthen newly developing links with two institutions: - Oswaldo Cruz Foundation, (FioCruz) Recife, Brazil. - The Christian Medical College (CMC), Vellore, India Our Training, Capacity Building and Long-Term Sustainability Theme will build on our excellent record in this area. This includes the many fellowships and PhD studentship supported through the above initiatives, our Masters course, with its emphasis on global health, and the annual Liverpool Neurological Infectious Diseases Course, which was established 2007 and has trained more than 500 junior and senior clinicians from 5 continents. The GHRG will support further staff and students from LMICs on the MRES and Brain Infection Courses. Online training and capacity building will be supported through the Global Health Research Network (see below) which will also hold a Global, Brain Infections Registry to allow institutions in other LMICs to become involved with this GHRG, thus extending its reach. D) PRIORITISING TOPICS – see also “Summary of Partnerships” Our international and other partners have been heavily involved in choosing topics and themes, from the onset of this grant call, using our shadow GHRG Steering Committee (see below), which established with the support of our NIHR HPRU. The balanced representation of partner countries on the Steering Group (see organogram) will ensure their continued input at every level. In addition, our choice of projects has been guided by the scientific outreach/Patient and Public Involvement (PPI) programmes of our partner institutions. We will ensure users remain heavily involved at all stages of the research cycle, through a PPI panel, made up of members of these programmes, chaired by the chief executive officer of one of these PPI charities. This builds on the Institute of Infection and Global Health’s award-winning Public Engagement Programme, the innovative Umoyo Nkukambirana, radio programme run by our researchers at Malawi since 2012, and compliments our other PPI work, such as that on Zika in Brazil, supported a £40K grant from the Wellcome Trust..

Lay abstract: BACKGROUND: Acute brain infections, such as meningitis and encephalitis, are a major cause of death and disability globally. There is relatively little global research expertise in tackling them. For many brain infections appropriate therapies exist, but doctors fail to diagnose, and thus treat them properly. Often basic but critical investigations, such as a lumbar puncture and microbiology, to examine the cerebrospinal fluid, are performed poorly, or not at all. Doctors are therefore faced with the choice of blindly overtreating for all possibilities (risking side effects, and antimicrobial resistance) or guessing at the diagnosis and treatment (which risks getting it wrong). Newer technologies offer the promise of diagnosing brain infections more accurately, more rapidly, with less reliance on skilled technicians, and ultimately more cheaply. AIMS and OBJECTIVES: Liverpool has an outstanding international reputation in brain infections research. Warwick has an internationally renowned Centre for Applied Health Research and Delivery. This GHRG will bring them together for the first time, along with leading research institutions in Malawi, India, and Brazil. The overall aim is to improve the diagnosis of acute brain infections in adults and children in these countries, to guide treatment and improve outcomes. We will also develop research capacity, and develop a broader network of hospitals interested in studying brain infections. This GHRG will thus establish the platform to generate follow on funding for further research projects, supporting long-term sustainability, Our research programme will comprise a series of projects in interlinked themes: THEME 1: Understanding the behaviours, knowledge, attitudes and practice of patients, families and health care workers to suspected brain infection. To understand the factors contributing to poor management we will examine social and structural barriers to care, through interviews, and focus group discussions. These studies will guide training, as well as intervention development. THEME 2: Improving early management through development of a compound intervention. Based on our findings in Theme 1, we will work with service users and providers to develop an intervention, made of different components, which improves patient management, and addresses underuse of lumber puncture, and inadequate laboratory methods. THEME 3: Strengthening diagnosis through pathogen discovery and host genomic approaches. Newer approaches to diagnosing brain infections are being developed in Liverpool and elsewhere. These include molecular methods to detect pathogens, and to look at human immune response patterns, which differ for different infections. We will develop such approaches to diagnose more patients. THEME 4: Policy, health economics and implementation. We will consider the funding impacts of any changes in care in advance of their development, to help determine if they are worth exploring, and the cost at which they might be implemented. Our patient and public involvement panel will ensure our research and its results have impact to reduce death and disability. THEME 5. Training, capacity building and long-term sustainability. This will include studentships on our Masters in Research, PhD exchange projects, short course staff training, and online research training modules, both generic and specific to brain infections, offered through our partner, the Global Health Research Network

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;8.1 ORGANISATION AND DELIVERY OF SERVICES;8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: INFECTION