EQATA: Equitable access to Quality Antibiotic Therapies in Africa

Globally antibiotic treatable infections account for 5.7 million deaths annually where the majority of this mortality burden falls on the populations of least developed low- and middle-income countries (LMICS). This significantly outweighs the 700k deaths, worldwide, currently attributed to antibiotic-resistant infections. However, the increasing threat posed by antimicrobial resistance will further extenuate the disproportionate health burden faced by LMICS. In Africa, deaths attributed to bacterial lower respiratory infections and diarrhoeal diseases together account for nearly 20 percent of all mortality. Strikingly this outnumbers the combined mortality rate of HIV/AIDS, TB and malaria. These headline figures underline the challenge faced by the health care systems in the least developed and lower middle-income countries of Africa. Here, access to frontline antibiotics is hampered by: i) substandard administration and/or unregulated over-the-counter availability, resulting in misuse and overuse; ii) weak supply chains resulting in chronic shortages; and iii) poor quality drugs and falsified medicines from a reliance on imports from generic API drug manufacturers alongside counterfeit drugs. These factors combined lead to unnecessary loss of human life and ever increasing drug resistance. As an example, multiple studies in hospital settings of Klebisella pneumonie isolates (a common urinary tract infection) from Kenya, Tanzania and Nigeria have shown multiple drug resistance (MDR) in 40-75% of cases; worryingly, this number also included samples showing extensive drug resistance. Combined, these studies demonstrate the problem faced across the three partner countries (Kenya, Tanzania, Nigeria), spanning East to West Africa, in accessing effective antibiotic therapies within the constraints of under developed healthcare systems. These nations do not have sustainable access to effective drugs, which we in the UK and the developed world take for granted.

This proposal will seek to address this unmet and urgent need partnering with Kenyan, Tanzanian and Nigerian institutes to investigate and apply innovative engineering, novel synthetic biological and chemical solutions toward improving health in Africa, by building capacity in these disciplines and providing sustainable solutions to an efficient and local well-stewarded antibiotic pipeline. This highly integrated project, links experts in industrial synthesis, industrial fermentation, engineering, synthetic biology, drug discovery and medicinal chemistry to build a sustainable antibiotic production pipeline. This will equip our African partners with the capability and capacity not only for equitable production of the most needed antibiotics (categorised by WHO as "access antibiotics") but also addressing our partners' dream for capacity building and training in the discovery of new antibiotics from their own natural resources.

The purpose of the EQATA proposal is to establish, by the end of the funding period, sustainable and equitable access to effective frontline semi-synthetic antibiotic compounds and to facilitate local capacity building in antibiotic discovery and characterisation. Thus, the whole focus of the consortium is on the pathway to impact. The initial end users are our partners in Kenya, Nigeria and Tanzania equipping them with key biotechnological infrastructure and training to enable follow-on discovery and implementation. This in turn will be create leverage for support and investment from biotechnology companies or pharmaceutical industries that have the expertise and financial resource to establish local production facilities in country and/or develop new discoveries towards clinical application, thereby reducing poverty through enhancing economic growth, employment opportunities and industrial development, striving to meet UN Sustainable Development goals. To initiate paving the way to such interactions and translation, as well bringing in skills and know-how, the consortium of academics and industrialists have considerable experience in taking compounds from discovery to development and are passionate in addressing equitable and fair access to effective bacterial treatments across all levels of society.

We will also ensure, through our engagement strategies that we remain focused on the needs of the ultimate end users: patients, focusing on compounds that are likely to address the most pressing clinical needs in our partner countries. In the process of achieving our objectives we will generate information and materials that are useful more widely. For example, we will collect, isolate and characterise a range of novel organisms that will widen our understanding of terrestrial soil ecosystems. We may uncover novel bioactives and biochemical pathways that will be of interest beyond the narrow frame of drug development. New chemical scaffolds will challenge the medicinal chemists to develop novel synthetic methods that will be useful more widely.
To ensure success in our higher-level goal we have built our consortium to deliver the core skills and training identified by our ODA partners for stewarded antibiotic discovery and production. This includes training in microbiology to identify and grow organisms from unique and biodiverse environments. Central to success is the merger of biological and synthetic chemistry to enable semi-synthesis of complex antibiotic compounds. While training in genomics metabolomics, and bioassay-guided compound isolation will provide the platform for long-term bioactive discovery. Thus by the end of the project, our partners will have the necessary multidisciplinary skillset to enable their continued discovery and development at the interface of chemistry and biology. At the same time UK partners will have developed a focused appreciation of the challenges and complexities faced by our African partners and the skills to design and implement sustainable and viable solutions for the long-term benefit of all.

Through a series of public engagement events we will engage local communities from all levels of society from school children to sicientists and medics across Kenya, Tanzania and Nigeria. These events will cover a range of topics from the importance of soil stewardship and its hidden treasure (the undiscovered microbes capable of making antibiotics) to implementing rapid antibiotic susceptibility testing.