EQATA: Equitable access to Quality Antibiotic Therapies in Africa

Lead Research Organisation: University of St Andrews
Department Name: Chemistry

Abstract

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.

Planned Impact

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.
 
Description We have completed the implantation of cost-effective fermentation reactor in the UK for deployment with our partners in Kenya, Nigeria and Tanzania. This is based on a commercially available brewing system adapted for the production of antibiotic precursors. This pilot study will then be translated to the field and adapted for local conditions to produce precursors to doxycycline. System purchased by Dzeha at Faulkner Institute/TUM. Erasto (NIMR, Tanzania) has identified new hot spring as potential source of unexplored bacteria. Collaboration agreement signed by all academic parties in September 2020 in line with Nagoya principals relating to ownership of discovered materials

Both PDRAs are in post after delay in recruiting due to Pandemic and GJF leading recovery (Director of Teaching, USTAN) effort over summer. Dr Yunpeng Wang recruited in June 2020 and Dr Marija Zacharova started January 2021. We have secured additional funding for Dr Zacharova to continue project with Wellcome Trust ISSF funding

Collaboration agreement in line with Nagoya principals ratified and signed by all parties.

Planned workshop events have been curtailed by COVID travel restrictions imposed by UK Government and University. We have held regular web meetings but hands-on device training and implementation has been problematic. Secondments for African partners original planned were cut from the grant due to continued COVID restrictions and the budget cuts imposed on the grant by EPSRC and the UK Government. In order to continue work we asked EPSRC for a 3 month no cost extension which was not approved. We have ran a very reduced training programme in February 2022 welcoming partners in St Andrews for research training in antibiotic discovery support by internal St Andrews-EPSRC funds. We have secured additional funding for Dr Zacharova to continue project with Wellcome Trust ISSF funding.

Through 2020 Agbo (University of Nigeria) impacted by civil unrest in country, Universities were closed for 9 months, reopening in September/October 2020. This does not appear to have been recognised by UKRI/EPSRC.
Exploitation Route The production of antibiotics in our partner countries is limited and the initial pilot study in antbiotic precursor production is designed to demonstrate that this is an acheivable and sustainable approach for development. This will provide a platform for further development of both production and discovery of new antibiotics in Africa and equip our partners with the necessary skill and technology to make such ventures viable. Dr Thomas Dzeha in Kenya has interest from several commercial partners to invest in spin-out.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Thomas Dzeha has been interviewed on Kenyan national TV to talk about the EQATA project and the role of TUM and Faulkenr Institute in marine bio discovery. This went out to a national audience at primetime. This has resulted in engagement with potential investors in Kenya about follow-on funding and spin-out investment. GJF took part in visit of CEFIC to St Andrews showcase capability in reactor design for sustainable antibiotic production in Africa Further impact is ongoing as continued restrictions in place have reduced research output through limited access to labs and in staff recruitment in the UK. Likewise planned training and educational visits to schools both in UK and Africa have been affected. Educational visits in Africa prevented by travel restricitons and school closures in UK have prevented hands-on practicals planned as part of the impact narrative.
First Year Of Impact 2020
Sector Chemicals,Education,Healthcare
Impact Types Societal

 
Description Internal St Andrews- EPSRC : Research and Training for Antibiotic Discovery and Production
Amount £17,000 (GBP)
Organisation University of St Andrews 
Sector Academic/University
Country United Kingdom
Start 11/2021 
End 03/2022
 
Description EQATA -Partnerships 
Organisation AbbVie Inc
Country United States 
Sector Private 
PI Contribution N/A
Collaborator Contribution AbbVie have been bought on board to provide technical expertise voluntarily in fermentative natural product production
Impact Too early in grant lifetime
Start Year 2020
 
Description EQATA -Partnerships 
Organisation Asynt Ltd
Country United Kingdom 
Sector Private 
PI Contribution N/A
Collaborator Contribution AbbVie have been bought on board to provide technical expertise voluntarily in fermentative natural product production
Impact Too early in grant lifetime
Start Year 2020
 
Description EQATA - Kenya: University of Nairobi 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Invited talk by Dr Thomas Dzeha at University of Nairobi on EQATA project
Year(s) Of Engagement Activity 2020
 
Description Kenya Marine and Fisheries Research Institute, Mombasa - Dr Thomas Dzeha 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Talk by Thomas Dzeha at Kenya Marine and Fisheries Research Institute on antibiotic discovery from Kenyan cyanobacteria
Year(s) Of Engagement Activity 2020
 
Description RSC Frank Warren Lecture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact RSC Frank Warren Lecture - University of Cape Town (via Zoom/Teams) 2/12/20 - Team members for UK, Kenya, Tanzania and Lebanon gave presentations on their work in area of antibiotic discovery
Year(s) Of Engagement Activity 2020
 
Description Scottish Natural Products (SNaPNet) - Launch and Networking event 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The multidisciplinary field of Natural Products includes topics such as synthetic biology, biomass and waste products and drug discovery (to name a few). We aim to create a multidisciplinary and cross-sectoral network that can work toward targets such as the Scottish Government's Net Zero by 2045 pledge and encourage the growth of the bioeconomy.
Drs Wang and Zacharova presented at this launch event - showcasing EQATA project
Year(s) Of Engagement Activity 2021
 
Description University of Kenya - invited talk by Dr Thomas Dzeha 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Tlak on antibiotic discovery from marine cyanobacteria as part of EQATA project
Year(s) Of Engagement Activity 2020