Partnership for a cross-disciplinary approach to the ecology of antimicrobial drug resistance in Kenya

Antibacterial resistance (ABR) is a significant threat to the future of effective healthcare and veterinary care. Globally, we are dependent on antibiotics for treating common as well as severe infections, but we abuse the value of these compounds by using them irrationally. In Kenya, as in many other countries, antibiotics are prescribed un-necessarily and without properly identifying the micro-organims being targeted, a fact that often leads to treatment failures. In agriculture, antibiotics are often used directly by farmers, as they are readily available on the market without prescription. Kenya is a country undergoing a demographic transition towards urbanisation, with over half the population expected to be in urban zones by the middle of this century. Many of these people are likely to live in low income settlements (eg 60% of residents of Nairobi, the capital, live in low income settlements = slums). Provision of high quality heath care is lacking in such sites. Further, with more people living in towns and cities, the pressure will be on farmers to produce more food more efficiently, and a key part of this - as has been the case in more developed economies - will be to use antibiotic drugs. These factors combine to produce a great deal of risk for highly drug resistant micro-organisms to emerge. Essential in preventing this will be to collect high quality data in hospitals and on farms, to understand what levels of resistance are present now, and how the organisms share their genes, a process that can result in rapid spread of resistant traits. A key aspects of this is also to understand how antibacterial drugs are used in practice, how they are procured and what drives individual and collective decision making about their use. Our programme will investigate these different aspects and work with partners in Kenya and internationally who make policy, in order to develop long term surveillance tools, plans to limit the spread of resistance and advice to the public to conserve these important drugs.

In Kenya and elsewhere, the antibiotic landscape for healthcare and livestock production is shaped by poor regulation and irrational drug use. There is a need for related evidence-based policy and the implementation plans for such policy. We will conduct in depth research in clinical and community settings to understand patterns of resistance, transmission of bacteria and their resistance determinants and genome based studies of resistance evolution. This will be combined with social and economic approaches to quantify the burden of antibacterial infection, the behavioural aspects of drug prescribing and use and the risks of mixing of bacterial populations between clinical settings, the community and the food systems that link them. Our approach is to build a strong network of antibacterial surveillance to monitor microbial ecology, and identify hotspots of selective pressure.
Our objectives are:
1) Surveillance in health care settings. We will establish longitudinal and cross sectional surveillance in clinical settings and explore changes in the diversity of bacterial flora with differing care pathways and drug exposure.
2) Community based longitudinal monitoring of ABR in livestock producers. We will recruit commercial farmers in to a series of longitudinal cohorts and monitor their bacterial ecology over time.
3) Microbiological dynamics within the household. We will explore the longitudinal dynamics of bacterial populations in humans, their animals and the immediate farm environment, as well as the products leaving the farms for market.
4) Microbiology and sequencing. We will develop robust microbiological and sequence-based approaches to quantifying bacterial diversity and drug sensitivity
5) Human behaviour and decision-making. We will emphasise the study of the social and economic environment in which antibiotic use takes place, both in domestic animals and humans and develop policy frameworks to limit irrational use.

In our Pathways to Impact document we have outlined partnerships we have enrolled with the ABR policy community in Kenya. Reviewing the recently published National Action Plan on Prevention and Containment of Antimicrobial Resistance, 2017-2022 (Government of Kenya, May 2017), developed in partnership with the Fleming Fund, it is clear that our proposed scientific research is in demand. Quoted below, the Plan's aims include:
- Increasing knowledge and understanding of antimicrobial resistance and antimicrobial use, especially in the healthcare, food, and livestock production sectors;
- Understanding the state of AMR emergence and prevalence, and use of antimicrobials (including surveillance and monitoring), and to assess the risk of emergence;
- Enhancing proper infection prevention and control;
- Ensuring antimicrobial stewardship (AMS) in order to reduce antimicrobial-resistant organisms;
- Accelerating research on the mechanism of AMR emergence and transmission, and its impact on social economy.
Our scientific outputs will be in demand by this policy community to take action in Kenya within the lifespan of the Consortium award, and our programme will be geared towards providing the best quality evidence available.

We will also have impact in training a cohort of future leaders in this field. All the co-Is are committed to training and capacity building, and all manage undergraduate, Masters and PhD level students with diverse funding sources. Aside from registered students, in Kenya, Fèvre's team manages annual cohorts of Kenya Field Epidemiology and Laboratory Training (FELTP) residents, young medical and veterinary clinicians who will benefit from our Consortium phase through specific training on the epidemiology and management of ABR. Already in the Development phase award we will engage 3 such individuals. Birungi, through the BecA Africa Bioscience Challenge Fund (ABCF) hosts emerging scientists from a range of national research institutions, providing mentorship, skills and access to top class facilities. Revathi hosts trainee microbiologists at Aga Khan; our Consortium phase would provide specific training in diagnosis and management of ABR for such trainees. Bukachi is currently engaged with UK-Kenya training in social anthropology. Kariuki is deeply engaged in training cohorts of young Kenyan microbiologists and laboratory technicians. Our activities in Kenya will also provide a template for trainees from across the Horn of Africa funded by our recent RCUK Capability and Capacity Strengthening Award (involving Universities of Liverpool, Nairobi, KEMRI and BecA). The programme will also enhance partnerships between the Kenya-based institutions, providing opportunities for further collaborative activity.