Drivers of Resistance in Uganda and Malawi: The DRUM Consortium

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

Abstract

The discovery and development of antibiotics is one of the great scientific achievements of the 20th Century, however it rapidly became clear that bacteria quickly become resistant to these lifesaving agents, and the spread of antibiotic-resistant bacteria is now a problem of global concern. The poorest nations on Earth frequently have the greatest burden of severe and life threatening infections, and these nations are likely to suffer most from the spread of untreatable bacteria. There is much that is unknown about how antibiotic resistance spreads globally and this is particularly true of sub-Saharan Africa, where diagnostic laboratories are not commonly available.
The "Drivers of Resistance in Uganda and Malawi" or DRUM Consortium will address how human behaviour and antibacterial usage in the home, around animals and in the wider environment in urban and rural areas of Uganda and Malawi contributes to the spread of antibiotic resistance in bacteria. The consortium is especially interested in the common bacteria E. coli and K. pneumoniae. E. coli is an example of a bacteria that often causes infections in the community, but may also spread around hospitals, whereas K. pneumoniae is a key cause of hospital acquired infections, particularly amongst vulnerable groups such as premature babies. We have chosen to study these bacteria together as they are from the same family and are able to share traits that make them resistant to antibiotics.
The DRUM consortium plans to investigate which aspects of behaviour are most important in spreading antibiotic resistance by surveying human behaviour in relation to antibiotics, water, sanitation and hygiene and by investigating bacterial behaviour in response to these stimuli. We plan to use cutting edge mathematical techniques to "model" which behaviours are most important and then use this information to work with policy experts in Uganda and Malawi to design potential interventions to prevent them from spreading further.

Technical Summary

The Drivers of Resistance in Uganda and Malawi, or DRUM Consortium aims to build an agent based model of the drivers of antimicrobial resistance transmission, using data from urban, peri-urban and rural settings in Uganda and Malawi to inform the model.

We will undertake five packets of work to build the model;
1. Longitudinally collect microbiological data from humans, animals and the environment of households at two levels of sampling intensity and genomically characterise the bacteria isolated;
2. Produce data on the intensity of antibiotic use across human and agricultural domains; the reasons for antibiotic use - and non-use - in different contexts; and drivers that are amenable to change;
3. As these are enteric pathogens, transmitted via the faecal oral route, we will provide a comprehensive outline of WASH behaviours and associated faecal exposure;
4. Determine the evolutionary trajectories of AMR development related to local antibiotic usage to understand if local usage and exposure patterns of antibiotics drive resistance emergence and persistence;
5. Quantify the economic burden from AMR and assess the value for money of potential interventions to tackle it.
At the same time, we will describe the barriers that exist in the AMR policy community and how these can be addressed in through implementing AMR strategic/action plans. The resulting information will be fed back to the policy community. We will use the relationships we develop in this workstream to develop and, in the future, trial interventions based on the output of the model.

Planned Impact

In Low and Middle Income countries (LMIC), there is a high incidence of severe bacterial infection and 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 morbidity and mortality, and is increasing selective pressure for the emergence of AMR pathogens. In many LMIC settings, extended spectrum betalactamase (ESBL) producing infections are locally untreatable due to unavailability of carbapenems or other reserve antibiotics.
The DRUM consortium will base its activities in urban, peri-urban and rural settings in Malawi and Uganda and is focusing on ESBL E. coli (ESBL-E) and K. pneumoniae (ESBL-K) bloodstream infections. These organisms share AMR phenotypes and genes and belong to the same family of bacteria. E. coli, however, are both community acquired and nosocomial, whereas K. pneumoniae are archetypal nosocomial AMR pathogens. Operating in urban, peri-urban and rural settings will enable us to evaluate AMR transmission at different human and animal population densities, with different levels of affluence, WASH infrastructure, burden of infectious diseases and different access to antimicrobials.
We propose a truly interdisciplinary approach, from laboratory to policy implementation to impact on this problem. To minimise AMR emergence and persistence, we will therefore describe the molecular epidemiology of AMR E. coli and K. pneumoniae in the human, animal and environmental context in which antimicrobials are used. Understanding the drivers of AMR transmission within the complex interplay between bacteria, humans, animals, and the environment is key to designing and implementing appropriate, safe, acceptable, and effective interventions. The DRUM Consortium envisages multiple pathways to impact.
1. We aim to have a AMR transmission model developed that can be used by policymakers to understand where evidence gaps remain and to test planned interventions. As part of this work, the model will be developed as a robust, user friendly piece of software. Our predictive model of AMR emergence to leverage fitness against pathogens. The model will be used to predict interventions that are most likely to succeed and this will inform applications to trial intervention strategies.
2. Our consortium includes a plan to identify key figures in AMR policy across multiple sectors in both settings that we will work with to disseminate our findings and to develop intervention strategies.
3. Packaging evidence into multiple 'products' through different formats and media. Our engagement strategy will be used to inform how to best package the evidence for each influential stakeholder. It will also inform the best time and route for the information to be delivered based on the stakeholder mapping. Targeted evidence products such as policy briefs and media briefings will be developed, and evidence dialogues will be held as appropriate. We will also discuss evidence at regional and global forums. Evidence will be disseminated to the research community through attendance at national and international conferences and peer reviewed publication.
We therefore expect that communities throughout East and Southern Africa will benefit from this study, through the development of strategies that will mitigate the spread of antimicrobial resistant bacteria. This in turn will reduce the incidence of locally untreatable bacterial infections.
 
Description BMGF/African Academy of Sciences (AAS)-Alliance for Accelerating Excellence in Science in Africa (AESA)
Amount $100,000 (USD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2019 
End 07/2020
 
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 MRC Doctoral Training Programme x 3 studentships
Amount £57,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2018 
End 11/2022
 
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