How do human and bacterial behaviour interact in urban and rural African environments to facilitate the stable acquisition of antimicrobial resistance

The development of antibacterials has saved millions of lives; however, the massive global usage of these agents has created huge pressure for bacteria to become resistant to these drugs and to cause infections that are difficult or impossible to treat. This, combined with the flow of drugs slowing profoundly, has made antibiotic resistance a threat to health of global importance. New approaches are necessary to reduce illness caused by resistant bacteria.
In Low and Middle Income countries (LMIC), there is a huge burden of severe illness caused by bacteria, a critical lack of clinics and hospitals to diagnose and appropriately treat bacterial infections and widespread availability of antibiotics without prescription. This situation is responsible for a huge amount of illness and is increasing the pressure on bacteria to become drug resistant. LMIC settings will be the last to benefit from new types of antibiotics and it is therefore of urgent importance to undertake research addressing antibiotic resistance in LMICs that aims to identify which are the most important causes or drivers of the development of drug resistance. This requires scientists from a variety of fields and with a variety skills, from the laboratory to policy implementation to work together.

We will therefore describe both where bacteria live when not causing infections, whether in humans, animals or the environment, and how antimicrobials are used and misused in humans animals and the environment to:

1. Determine ways of using antibiotics make resistance come at a cost rather than as a benefit to bacteria
2. Develop ways of using antibiotics across all sectors that both improves access for people that really need them, but protects medicines of last resort in a manner acceptable to governments, communities and doctors to minimise the local emergence of resistance;
3. Identify ways in which different parts of government, the health and research sectors can more effectively work together to reduce antibiotic resistance at national and district level, both within and between human and animal health and the environment.

The development of antibacterials has saved millions of lives; however, the massive global usage of these agents has created huge selective pressure for the emergence of antibacterial resistant (ABR) bacteria and drug resistant infection (DRI). This, combined with the flow of new antimicrobial agents slowing profoundly, has made ABR a public health threat of global importance and new approaches are necessary to reduce morbidity and mortality from DRI.
In Low and Middle Income countries (LMIC), there is a huge burden of severe bacterial infection, a critical lack of accessible health system infrastructure to diagnose and appropriately treat bacterial infections and widespread availability of antimicrobials without prescription. This situation is responsible for a huge burden of disease, and is increasing selective pressure for ABR emergence. LMIC settings will be the last to benefit from new classes of antimicrobials and it is therefore of urgent importance to undertake research addressing ABR in LMICs that aims to identify drivers and interrupt transmission pathways of ABR pathogens. Only a truly interdisciplinary approach, from laboratory to policy implementation can impact on this problem. We will therefore describe the spatial and molecular epidemiology of ABR pathogens in the human, animal and environmental context in which antimicrobials are used, to:

1. Determine treatment strategies that leverage the fitness cost to pathogens of acquiring ABR thus minimising the emergence and persistence of resistance
2. Develop antimicrobial management and usage strategies across all sectors that both improve equity of access and restrict reserve agents in a manner acceptable to governments, communities and end users to minimise the local emergence and persistence of resistance;
3. Identify and addresses barriers to sustainable delivery of collaborative actions to address ABR at national and district level, both within and between human and animal health systems.

Key impacts from the development phase award will include a strengthening of existing links with policymakers across relevant ministries from its start, and it will be used to strengthen the capacity of national and local systems to deliver coordinated ABR interventions across human, animal and environmental sectors, including building South-South cooperation. The applicants aim to secure a development award and to submit a consortium application.
Key impacts from a consortium phase application will include:
1) A South-South cooperation between College of Veterinary Medicine Makerere (COVAB) University of Malawi (UNIMA) that will enhance existing cooperation between Makerere and UNIMA.
2) A predictive model of AMR emergence to leverage fitness against pathogens, which will provide robust evidence to inform treatment policy to avoid AMR emergence.
3) A validated model of AMR transmission that will provide robust evidence to design interventions to interrupt AMR transmission.
4) An assessment of capacity, and opportunities to improve multi-sectoral policy development and community acceptability to provide an evidence base for capacity strengthening needs and evidence based, effective and feasible multi-sectoral antimicrobial stewardship and hygiene policies/guidelines.
6) A platform which allows continent-wide data input to inform AMR surveillance to support the dissemination of reliable, timely evidence to hasten mitigating actions and response.
7) Piloted interventions in urban and rural settings to interrupt transmission of AMR pathogens to reduced drug resistant infection and maintain antimicrobial effectiveness if interventions are taken to scale.
8) An economic model to estimate economic burden of AMR and returns on investment from potential interventions to minimise impact including budget impact assessment and financial planning; insights influencing the political economy of decision-making and a validated framework to estimate economic impact of future interventions.