The discovery and development of antibiotics is one of the great scientific achievements of the 20th Century, however it rapidly became clear that bacteria quickly become resistant to these lifesaving agents, and the spread of antibiotic-resistant bacteria is now a problem of global concern. The poorest nations on Earth frequently have the greatest burden of severe and life threatening infections, and these nations are likely to suffer most from the spread of untreatable bacteria. There is much that is unknown about how antibiotic resistance spreads globally and this is particularly true of sub-Saharan Africa, where diagnostic laboratories are not commonly available. The "Drivers of Resistance in Uganda and Malawi" or DRUM Consortium will address how human behaviour and antibacterial usage in the home, around animals and in the wider environment in urban and rural areas of Uganda and Malawi contributes to the spread of antibiotic resistance in bacteria. The consortium is especially interested in the common bacteria E. coli and K. pneumoniae. E. coli is an example of a bacteria that often causes infections in the community, but may also spread around hospitals, whereas K. pneumoniae is a key cause of hospital acquired infections, particularly amongst vulnerable groups such as premature babies. We have chosen to study these bacteria together as they are from the same family and are able to share traits that make them resistant to antibiotics. The DRUM consortium plans to investigate which aspects of behaviour are most important in spreading antibiotic resistance by surveying human behaviour in relation to antibiotics, water, sanitation and hygiene and by investigating bacterial behaviour in response to these stimuli. We plan to use cutting edge mathematical techniques to "model" which behaviours are most important and then use this information to work with policy experts in Uganda and Malawi to design potential interventions to prevent them from spreading further.

In all countries, difficult decisions are needed on how health care is financed, organised and provided for the benefit of populations. Decisions include how to determine and to secure appropriate levels of funding for health care; which interventions to fund; how to pool and distribute resources between geographical localities; and when to invest resources in strengthening key components of the health care system to improve the quality and coverage of existing interventions versus introducing new effective interventions. All health care systems face the reality that the cost of the available opportunities to enhance benefits always exceeds the available funding. The decisions made affect the kinds of interventions provided, who receives health care, who goes without and, ultimately, the magnitude of benefits to populations. Resources are particularly scarce in low-income countries. For example, total health care spending is US$39 per capita in Malawi, a country that is also highly dependent on aid, representing about 62% of that funding, resulting in local preferences regarding how resources are used having to be balanced against donors' priorities. In sub-Saharan African countries (such as Malawi), the opportunities for improving population benefits are great, but the consequences of getting these decisions wrong are potentially severe in terms of forgone benefits. Thanzi la Onse (TLO) provides an integrated programme of multi-disciplinary research to inform decisions in low-income settings on health care resource allocation. This challenging policy area lies at the intersection of health, economics and politics. The structure of this proposed research reflects that reality. The centrality of 'value for money' in determining domestic and international development activities is now widely accepted, particularly so in low-income countries, but tackling the challenges of policy formulation and resource allocation decisions, given the evidential and institutional constraints faced by health care systems in poor countries, remains an urgent research priority. This work will build research capability to address this need by evaluating alternative policy options in terms of locally-realised health benefits achieved through alternative spending commitments. This requires evaluating the benefits of any commitments and also what is foregone as a result of resource constraints prevailing in health care systems. Understanding the magnitude and distribution of such outcomes is key to ensuring value for money for spending on health. The value of specific interventions needs to be understood within the context of the health care system in which it is delivered. TLO will study the inter-relationships between the impact of different interventions and policies on population benefits and the range of characteristics of the system in terms of how it funds and delivers care, its weakness and constraints. Research to support decision-making also needs to recognise the potential barriers to its acceptance and implementation, requiring close links with policy-makers. Themes of research in epidemiology and health economics will be complemented by a third theme on politics and governance; realising inter-disciplinary complementarities which hitherto have not been fully exploited. The initial focus of TLO will be working with policy-makers and informing resource allocation decisions in Malawi and Uganda. This will include modelling the whole health system in Malawi to fully reflect its limited resources, the needs and characteristics of the population and the value of competing claims upon resources. Activities will receive international attention and inform the priorities of international organizations. Over the longer term, the programme is expected to work closely with policy-makers across the east, southern Africa region and beyond to ensure health care delivery is as fully informed as possible by leading research methods.

Severe acute malnutrition (SAM) in children under five years of age is associated with a very high in-hospital mortality. However, they also have a very high risk of dying after they have been discharged from the hospital to continue treatment in community health facilities. Almost half of them do not survive the first 6 months post-discharge. The cause of death likely reflects the high risk of infections during a time when their nutritional status and immunity have not yet fully recovered. It is hypothesised that malaria infection post-discharge may be an important contributor in areas with moderate to high malaria transmission. Our group recently demonstrated that providing three months of malaria chemoprevention during this post-discharge period to children with severe anaemia, another high-risk group of post-discharge mortality, prevented 3 out of every 4 post-discharge deaths. The World Health Organisation (WHO) now recommends post-discharge malaria chemoprevention (PDMC) for hospitalised children with severe anaemia living in malaria-endemic areas. Children with SAM are likely to benefit from this intervention. However, PDMC has not yet been evaluated in this high-risk group. We propose a clinical trial involving 538 children with SAM in Uganda and Malawi. Hospitalised children under 5 years with SAM will be randomised to receive either 4 months of weekly malaria prophylaxis with an antimalarial called dihydroartemisinin-piperaquine or a placebo after being discharged from the hospital. The aim is to determine if malaria prophylaxis reduces their risk of dying or being re-hospitalised. Children will be followed up on for a total of 6 months. The study also aims to assess the safety of weekly prophylaxis dihydroartemisinin-piperaquine by conducting nested cardiac monitoring using ECGs and measuring the drug levels at specific time points. The study will also have a health-economic component to determine the potential cost-effectiveness of PDMC. Lastly, we shall assess whether this intervention is acceptable to healthcare providers and the parents or guardians. The study is designed to inform national ministries of health and WHO. We hope our findings will result in a policy recommendation for PDMC in children with SAM in malaria-endemic countries in Africa, similar to our previous PDMC studies in children with severe anaemia. This study provides a platform for 4 PhD students from Africa and supports the development of a specialised laboratory technique for assessing antimalarial drug levels in Africa. The project will take 4 years to complete and involves partners from Malawi, Uganda, South Africa, the UK, and Norway.

Globally, more than a quarter of children under the age of five years are stunted (undernourished). Stunted children experience lifelong problems with their health and are more likely to die early. The time at which an infant transitions from receiving only breastmilk to needing additional foods (complementary feeding) has been shown to be associated with increasing problems with stunting. Currently only 22% of Kenyan and 8% of Malawian children aged 6-23 months receive the minimum acceptable diet, down from 39% (Kenya) and 19% (Malawi) between 2008 and 2014. It is estimated that interventions which promote optimal infant and young child feeding (IYCF) practices could prevent 20% of deaths in under-fives in countries with high levels of child deaths. Approximately one-third of urban residents in low and middle income countries live in slums, with an additional 100,000 moving in daily. Children living in slums are more likely to suffer from under-nutrition than other urban children. Nevertheless the literature tells us that there is a lack of evidence regarding nutrition interventions in slum environments, and almost no evidence regarding the potential for 'nutrition-sensitive' interventions that target the drivers of poor nutrition such as poverty, cultural and social practices, and poor physical environments. Successful design of these types of intervention requires a well-integrated interdisciplinary approach. In addition to nutrition expertise, contributions from other disciplines are needed to understand the cultural, social, physical and economic environments that influence IYCF practices. We therefore propose an interdisciplinary network with the aim to produce evidence to drive future research and inform policies to improve the nutritional status of IYC living in poverty in sub-Saharan African countries (SSA) experiencing rapid urbanisation. The network is led by Loughborough University with Kenyan partners at the African Population and Health Research Centre and Malawian partners at the University of Malawi and The Lilongwe University of Agriculture and Natural Resources as well as UK partners at The Universities of Sheffield and Southampton. The specific network objectives will be to: 1) Prepare a rapid review of evidence documenting interventions for the urban poor to improve the nutrition of IYC in SSA; 2) Convene the first network workshop (to include stakeholders) to firstly guide analysis of existing data sources on this topic, to secondly consider the current evidence base and policies identified in the rapid review and finally to ask key stakeholders to identify highest-ranking evidence/research gaps for improving IYC feeding programmes and policies; 3) Undertake analyses of existing data from demographic and health surveys in sub-Saharan Africa and pre-existing data from slums in Nairobi to explore how the various drivers of IYCF practices are influenced by urbanisation and to consider whether those drivers vary for the urban poor compared to other urban populations; and finally 4) Facilitate end-of-project workshops to develop research proposals informed by evidence from the first three objectives and to present findings of the secondary analysis and discuss these with stakeholders (including Ministries of Health, NGOs, communities) and policy-makers. The network will also foster the development of skills in data analysis and evidence synthesis in early career researchers in the UK, Malawi and Kenya, thus helping to ensure a sustainable group with potential for evolving future leadership. In the longer term we will develop a UK-Africa interdisciplinary network with expertise to support interventions to promote optimal IYCF practices in rapidly urbanising environments. It is envisaged that such interventions will improve the human capital of developing countries by reducing under nutrition, thus promoting optimal cognitive and physical development, and thereby increasing prospects for economic prosperity.

This research partnership involves a two-year programme of work focused on the ways in which rapidly changing cultures of poultry meat consumption and agricultural systems in particular Low and Middle Income Countries (LMICs) shape antibiotic use/misuse in farming, with implications for tackling the global antimicrobial resistance (AMR) health challenge. AMR, or in lay terms drug-resistant infections, is one of the top five priorities for the World Health Organization (WHO). The 2016 O'Neill report into 'Tackling Drug-Resistant Infections Globally' warns that if the challenge is left unaddressed, deaths resulting from AMR on a global scale are predicted within the next three decades to reach some 10 million per year. AMR in agriculture and food systems is a critical area of concern, with increasing cases reported of strains of bacteria such as E.Coli, Campylobacter and Salmonella developing resistance to particular groups of antibiotics. While antibiotics are a necessary tool to maintain health and welfare on the farm, the problem is their inappropriate and disproportionate use in animals, thereby reducing availability for humans and also catalysing resistance. The first aim of the research partnership is to evaluate the relationships between changing urban diets incorporating increased meat consumption, transforming food systems and the use/misuse of antibiotics in agriculture. It will do so through a focus on the poultry sectors of Kenya and Malawi, in particular the urban contexts of Nairobi and Lilongwe, given the rapid rise of poultry production and consumption in both places and the increased and weakly regulated use of antibiotics in production. Moreover, Kenya and Malawi are a Lower Middle Income Country and a Least Developed Country, respectively, on a continent predicted to see the highest mortality rate from AMR by 2050. The second aim is to generate culturally and geographically sensitive approaches to antibiotic reduction and stewardship initiatives in these contexts, in ways that improve implementation of their governments' AMR National Action Plans. The premise of the research is that policies and targets for the reduction of antibiotic misuse in agriculture, whilst shaped by the WHO and a 'One Health' agenda, are most likely to be effective if their implementation is responsive to the specific pressures, constraints and opportunities experienced by farmers in the context of the particular food systems in which they are embedded, and to the cultural values shaping everyday farming practice. The partnership brings together an interdisciplinary team and wider network of researchers and policy-makers across Kenya, Malawi and the UK. The core team represent the African Population and Health Research Center in Nairobi, the University of Malawi, Newcastle University, Southampton University and UCL. Collaboration in the partnership involves dialogue between the disciplines of Geography, History, Epidemiology, Medicine, Anthropology, Microbiology and Art to understand how cultural values and practices are integral to antibiotic use/misuse in the particular food systems and poultry sectors of Kenya and Malawi. The partnership also involves influential AMR policy institutions on its advisory board, including the UK's Food Standards Agency, the UN's Codex Alimentarius, Malawi's Ministry of Health and the International Livestock Research Institute in Kenya as Project Partners. The model for the partnership involves a programme of interwoven scoping research, involving secondary and primary data collection in Kenya and Malawi, and three intensive workshops in London, Nairobi and Lilongwe. Research will develop understanding of the embeddedness of antibiotic use and AMR awareness in everyday cultures and practices of subsistence and commercial farming. From this research, recommendations will be made to Kenyan and Malawian AMR policy-makers regarding culturally-sensitive and effective approaches to antibiotic stewardship.