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

Lead Research Organisation: Liverpool School of Tropical Medicine
Department Name: Clinical Sciences

Abstract

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.

Technical Summary

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.

Planned Impact

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.

Publications

10 25 50
 
Description Identifying Barriers to collaborative action on AMR in Malawi
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description Drivers of Resistance in Uganda and Malawi: The DRUM Consortium
Amount £3,046,155 (GBP)
Funding ID MR/S004793/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 05/2018 
End 01/2021
 
Description JPIAMR Network of European and African Researchers on AMR (NEAR-AMR)
Amount £44,000 (GBP)
Funding ID MR/S037640/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2019 
End 02/2019
 
Description AFIDEP 
Organisation African Institute for Development Policy
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies. Organised and hosted a strategic planning and series of stakeholder engagement meetings in Kampala in January 2019
Collaborator Contribution Lead on workstrand 8 - Identifying and addressing barriers between in-country sectors involved in AMR control for the delivery of appropriate policy. AFIDEP has contributed widely to programme management meetings, development of the WS8 workplan and budget and in design and progress of a policy engagement strategy. AFIDEP also attended a Workstrand 2 strategic planning meeting in Kampala, and associated stakeholder engagement meetings in January 2019
Impact Signed consortium agreement, and contribution to a multi-disciplinary workplan creation, incorporating a one-health approach. Standard Operating procedures written. Ethical approval obtained for all DRUM in Liverpool and Malawi, Uganda under revision. Expert review group appointed and approved, with draft terms of reference.
Start Year 2018
 
Description CEH 
Organisation Natural Environment Research Council
Department Centre for Ecology & Hydrology (CEH)
Country United Kingdom 
Sector Academic/University 
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies.
Collaborator Contribution Attendance at monthly PMC meetings. Inputs to workstrand 2 - Detailed, longitudinal, microbiological surveillance of humans, animals and the environment to describe the dynamics of ESBL-E and ESBL-K and their ecological niche - specific contribution to environmental microbiology.
Impact Signed consortium agreement, contribution to a multi-disciplinary workstrand incorporating a One-Health approach (human microbiology, environment and animal/veterinarian health)
Start Year 2018
 
Description IDI 
Organisation Makerere University
Department Infectious Diseases Institute
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies.
Collaborator Contribution Inputs to development of the workplan for Workstrand 2 - Detailed, longitudinal, microbiological surveillance of humans animals and the environment to describe the dynamics of ESBL-E and ESBL-K and their ecological niche Inputs to development of the workplan for Workstrand 5 - Understanding the drivers of water sanitation and hygiene practices and their relation to the faecal-oral transmission of ESBL-E and ESBL-K Inputs to development of the workplan for Workstrand 7 - Understanding the economical implications of antimicrobial resistance Attendance at monthly programme management meetings and at the kick off meeting in Liverpool in July 2018, also hosting of the Workstrand 2 development meeting in Kampala in January 2019.
Impact Signed consortium agreement, contribution to a multi-disciplinary workstrand incorporating a One-Health approach (human microbiology, environment and animal/veterinarian health). Standard Operating procedures written. Ethical approval obtained for all DRUM in Liverpool and Malawi, Uganda under revision. Expert review group appointed and approved, with draft terms of reference. DRUM plans presented at: 1) 3rd Annual National AMR Conference (21-22 Nov 2018), Kampala, Uganda and 2nd Global Network of AMR and IPC Symposium (4-7 Mar 2019), Kampala, Uganda.
Start Year 2018
 
Description Lancaster - CHICAS 
Organisation Lancaster University
Department Centre for Health Informatics, Computing, and Statistics (CHICAS)
Country United Kingdom 
Sector Academic/University 
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies.
Collaborator Contribution Leading Workstrand 6: Dynamical agent-based modelling of AMR in Uganda and Malawi Specific support to development of the workplan and budget for WS6 including the early development of a cohesive model-focused approach and the creation of the dataverse, an online data storage platform which is GDPR compliant,secure, publishable and self-managed. Attendance at monthly programme management meetings and at the kick off meeting in Liverpool in July 2018 as well as at the WS2 strategic planning and stakeholder engagement meeting in Kampala in January 2019.
Impact Signed consortium agreement, online dataverse data bank, contribution to a multi-disciplinary workstrand incorporating a One-Health approach (human microbiology, environment and animal/veterinarian health)
Start Year 2018
 
Description MLW 
Organisation Wellcome Trust
Department Malawi-Liverpool Wellcome Trust Clinical Research Programme
Country Malawi 
Sector Charity/Non Profit 
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies.
Collaborator Contribution Lead workstand 2: Detailed, longitudinal, microbiological surveillance of humans, animals and the environment to describe the dynamics of ESBL-E and ESBL-K and their ecological niche. Attendance at monthly programme management meetings and at the kick off meeting in Liverpool in July 2018 as well as at the Workstrand 2 strategic planning meeting in Kampala in January 2019.
Impact Signed consortium agreement, contribution to a multi-disciplinary workstrand incorporating a One-Health approach (human microbiology, environment and animal/veterinarian health). Standard Operating procedures written. Ethical approval obtained for all DRUM in Liverpool and Malawi, Uganda under revision. Expert review group appointed and approved, with draft terms of reference.
Start Year 2018
 
Description Makerere CHS 
Organisation Makerere University College of Health Sciences
Country Uganda 
Sector Academic/University 
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies.
Collaborator Contribution Inputs to development of the workplan for workstrand 2 - Detailed, longitudinal, microbiological surveillance of humans, animals and then environment to describe the dynamics of ESBL-E and ESBL-K and their ecological niche. Inputs to development of the workplan for workstrand 8 - Identifying and addressing barriers between in-country sectors involved in AMR control for the delivery of appropriate policy . Attendance at the monthly Programme Management meetings, at the kick-off meeting in Liverpool (July 2018) and at the Workstrand 2 development meeting in Kampala in January 2019.
Impact Signed consortium agreement, and contribution to a multi-disciplinary workplan creation, incorporating a one-health approach. Revised budget to allow for new strategy for policy engagement work in both research countries. Standard Operating procedures written. Ethical approval obtained for all DRUM in Liverpool and Malawi, Uganda under revision. Expert review group appointed and approved, with draft terms of reference.
Start Year 2018
 
Description Sanger 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies.
Collaborator Contribution Inputs to the development of the workplan for workstrand 2: Detailed, longitudinal, microbiological surveillance of humans, animals and the environment to describe the dynamics of ESBL-E and ESBL-K and their ecological niche. Attendance at monthly programme management meetings and at the kick off meeting in Liverpool in July 2018
Impact Signed consortium agreement, contribution to a multi-disciplinary workstrand incorporating a One-Health approach (human microbiology, environment and animal/veterinarian health). Standard Operating procedures written. Ethical approval obtained for all DRUM in Liverpool and Malawi, Uganda under revision. Expert review group appointed and approved, with draft terms of reference.
Start Year 2018
 
Description Strathclyde 
Organisation University of Strathclyde
Department Department of Civil and Environmental Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies.
Collaborator Contribution Leading on the development of an in-depth workplan and budget for workstrand 5: Understanding the drivers of water, sanitation and hygiene practices and their relation to the faecal-oral transmission of ESBL-E and ESBL-K. Coordinating work with MLW and IDI for in-country data collection, and working with the social science teams to ensure strong data on drivers of AMR. Attendance at monthly programme management meetings and at the kick off meeting in Liverpool in July 2018 as well as at the WS2 development meeting in Kampala in January 2019
Impact Signed consortium agreement, contribution to a multi-disciplinary workstrand incorporating a One-Health approach (human microbiology, environment and animal/veterinarian health). Standard Operating procedures written. Ethical approval obtained for all DRUM in Liverpool and Malawi, Uganda under revision. Expert review group appointed and approved, with draft terms of reference.
Start Year 2018
 
Description University of Liverpool 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution The partnership has been confirmed contractually, with a consortium agreement containing workplans and agreed budget. Partners have attended monthly Programme Management Meetings and a kick off meeting in Liverpool in June 2018 to devise these workplans, agree trans-disciplinary working practices and approve publications strategies.
Collaborator Contribution Lead on workstrand 7: Understanding the economic implications of antimicrobial resistance. Attendance at monthly programme management meetings, a Workstrand 2 strategic planning and stakeholder engagement meeting in Kampala in January 2019 and at the kick off meeting in Liverpool in July 2018.
Impact Signed consortium agreement, contribution to a multi-disciplinary workstrand incorporating a One-Health approach (human microbiology, environment and animal/veterinarian health). Standard Operating procedures written. Ethical approval obtained for all DRUM in Liverpool and Malawi, Uganda under revision. Expert review group appointed and approved, with draft terms of reference.
Start Year 2018
 
Description A poster presentation at the Microbiology Society conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact A poster presentation at the Microbiology Society conference
Year(s) Of Engagement Activity 2018
 
Description A poster presentation at the Society of Applied Microbiology Early Career Scientiest symposium 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact A poster presentation at the Society of Applied Microbiology Early Career Scientiest symposium
Year(s) Of Engagement Activity 2018
 
Description Introductory talk on AMR in LMICS at Bristol University for the National PhD Training Scheme in AMR funded by the Medical Research Foundation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact First training cohort on the National PhD Training Scheme in AMR funded by the Medical Research Foundation. Purpose was to give an overview of the AMR situation in different socioeconomic regions. Positive feedback received. Asked to present at the Sepsis 2109 conference in Birmingham on this topic as a result.
Year(s) Of Engagement Activity 2018
 
Description Invited participant at the 5th British-German Frontiers of Science Symposium 2018 March 21 - 24, 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The Alexander von Humboldt Foundation, the Young Academy, and the Royal Society collaborate to organize the 5th British-German Frontiers of Science Symposia. The conference brings together approximately 60 outstanding young British and German scientists (with up to 15 years of postdoctoral experience), half from the Great Britain and half from Germany.

The participants discuss advances and opportunities of various scientific disciplines, such as chemistry, geosciences, biology, mathematics, physics, and neuroscience. During the conference, 18 scientists from the United Kingdom and Germany introduce the scientifically diverse audience to the excitement of their fields, place their research in larger scientific contexts, illustrate research at the cutting-edge of other disciplines, and stimulate an interdisciplinary discussion among all participants. The conference is intended to encourage the exchange of knowledge across disciplines and to provide opportunities for British-German collaborations and networking. The first British-German FoS symposium took place in Wyboston (UK) in 2006, the second symposium in Potsdam (Germany) in 2008, the third at the Kavli Royal Society International Centre in North Buckinghamshire (UK) and the fourth symposium in Potsdam (Germany).
Year(s) Of Engagement Activity 2018
URL https://www.humboldt-foundation.de/web/brigfos-2018.html
 
Description The importance of RSTMH on the issue of drug resistant infections 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact It is appreciated that drug resistant infections (DRIs) are not as geographically constrained as their human, animal or plant hosts and that there are many countries and areas of the world where the effects of DRIs will be disproportionally felt due to limited resources and healthcare-infrastructure, as well as a reduced capacity and capability to monitor and respond to disease.

To limit the consequences of DRIs, a collective response is needed that similarly does not respect geographical and political boundaries.

The international challenge of DRIs is increasingly illustrated by many national and international funding bodies highlighting it as a priority area of research, with an increase in collaborative opportunities to apply for support for investigations into both the problem of DRIs and potential solutions.

Recognition of the multi-disciplinary nature of DRIs is also increasing within the funding landscape and has had a transformative effect on the perception of the DRI problem, at least among many of those applying for funds to try and understand and fix it.

This is where RSTMH plays a key role. RSTMH membership maps well to the areas of greatest vulnerability from drug resistance.

The Society's roles in terms of highlighting priority areas for research, education, dissemination of research findings via publications and advertising funding opportunities is also an important link between research groups, healthcare workers and clinicians, and policy stakeholders across the entire global One Health spectrum.
Year(s) Of Engagement Activity 2018
URL https://rstmh.org/blog/2018/sep/17/importance-rstmh-drug-resistant-infections