Severe acute malnutrition (SAM) causes 1 million deaths in children annually by making children susceptible to common infections. The World Health Organisation (WHO) recommends that children with SAM should receive antibiotics together with nutritional rehabilitation. Children with SAM and complications including signs of infection or severe metabolic disturbance are referred for hospital admission. However, most admissions with SAM present directly to hospital because of severe illness, and their SAM is only detected during clinical assessment. At the four hospital sites for the proposed trial, between 15% and 18% of paediatric admissions between the ages of 2 and 59 months have SAM. In sub-Saharan Africa, up to 30% of children admitted to hospital with complicated SAM die, usually from severe infection. Mortality is highest amongst those who also have HIV infection. There are reports that bacteria isolated from children with SAM, when tested in the laboratory, are often not susceptible to the recommended first-line antibiotics. In Kenya we have conducted long term surveillance of bacterial infections. Amongst children with SAM, non-susceptibility has risen: in the last 5 years, more than one third of bacteria isolated at admission to hospital are non-susceptible to the recommended antibiotics. Because children with SAM are vulnerable to infection, this to result in death rather than simply a prolonged hospital stay. An alternative antibiotic, ceftriaxone, is cheaper the currently recommended combination and only has to be given once a day instead of four times. Much less resistance to ceftriaxone is reported. Ceftriaxone would be used as first line treatment if such a child were admitted to hospital in the UK. At first sight, it seems that ceftriaxone would be a more appropriate antibiotic, and it could reduce deaths. However, a significant concern is that ceftriaxone is known to rapidly induce resistance to multiple classes of antibiotics. This could mean that subsequent infections could be harder, and more expensive, to treat. Furthermore, studies have not shown a clear relationship between laboratory susceptibility testing and actual outcomes. In determining policy for empiric antimicrobials for this vulnerable population, potential benefits of reduced mortality, quicker recovery and reduced costs must be weighed against potential risks of infections that are difficult and expensive to treat. There is currently no evidence to inform this decision. A second question in the antibiotic treatment of SAM is the value of metronidazole. Current WHO guidelines suggest that metronidazole may be optionally used although it has never been tested in a clinical trial. It is effective against bacteria that cause abnormal overgrowth in the small bowel, and against gut parasites such as Giardia. These conditions are common amongst children with SAM and may cause malabsorption of nutrients and diarrhoea. Treating them improve nutritional recovery. Results of small studies suggest this may be the case. However, metronidazole can cause nausea, vomiting and other toxicities which could impede nutritional recovery. We propose an efficiently designed trial to test both ceftriaxone and of metronidazole against standard care for the outcomes of mortality and nutritional recovery. First we will determine the optimal dosing for the drugs in malnourished children. We will carefully investigate children for infections and the antibiotic susceptibility of bacteria isolated determined. An economic analysis will measure the cost-benefit ratio of each strategy and overall costs of treatment for SAM. The trial will be run at 2 rural and 2 urban hospitals in Kenya. The results are expected to have direct impact on antibiotic policy for the management of SAM in hospitals in Africa and will provide unique information that will contribute to global efforts to combat the threat of antimicrobial resistance.

Citizens in LMICs experience a range of problems with public and private health services: from poor quality of services to rights violations. In spite of numerous calls and interventions for increased community participation in health, service users and citizens often do not have adequate opportunities to engage with the system about their problems and induce appropriate responses and remedies. Responsiveness to citizens' rights and needs is an essential quality of health systems, and is necessary in order to provide inclusive and accountable services, ensure the social rights of citizens and improve the quality of services. Mechanisms for feedback and response are varied and result in dispersed and sometimes conflicting feedback. These range from conventional facility-based complaints boxes and exit surveys to strategies such as community report cards, social audits, and hotlines. Citizen feedback at community-level has also been sought by implementing health facility committees, intersectoral forums, and community monitoring systems. Growing access to information technology in LMICs has often empowered citizens to raise their concerns through social media, the mainstream press, and even through social protest. Health system responsiveness is gaining global currency as an intrinsic goal of health systems alongside service delivery outcomes, financial fairness and equity. However our current understanding of health system responsiveness is extremely limited, and there is a significant evidence gap about the structure, implementation and effectiveness of citizen feedback and the related response mechanisms about health services currently in place in LMICs. In this study, we aim to address these knowledge gaps by asking: What policies and mechanisms (formal and informal) work for receiving and responding to citizen feedback on health systems in South Africa and Kenya? How can health systems responsiveness be strengthened towards the development of learning, equitable health systems? The proposed study is an interdisciplinary mixed methods study, running from 2018 to 2020. The study will be conducted in three phases, and we will apply several, primarily qualitative methods and tools. The first phase will consist of 'mapping' of policies, feedback mechanisms and pathways for system responsiveness in the study provinces (as well as theoretical and methodological framing relating to responsiveness). Many governments in LMICs are recognising the pressing need to improve health system responsiveness, and both countries in this study have recently implemented significant policy reforms aimed at improving responsiveness to citizen feedback on health services. We will capitalise on this window of opportunity, with the second in-depth phase consisting of case studies in each country, tracking the implementation experience of a particular innovation in this area. The third phase will focus on knowledge translation and cross-country comparison. This project will contribute to a deeper and more systematic understanding of health system responsiveness in South Africa and Kenya, with relevance for other comparable LMICs. By applying an embedded approach to HPSR, it is intended that the research will also have a health system strengthening effect: creating space for reflective practice, strengthening feedback and response within the system, and improving decision-making opportunities for HS leaders. Therefore, this study on responsiveness to citizen feedback should also improve the responsiveness of the health systems in which it is implemented. In each country, we have partnered with policy decision-makers engaged in implementing reforms for greater health system responsiveness, and this study will directly help bring about improvements in these policies. We will also engage with other health system and civil society leaders to identify strategies to strengthen health system responsiveness.