New data driven solution to Antimicrobial Resistance (AMR) in LMICs.

Our research in Bangladesh examines how antimicrobial resistance genes (ARG) evolve across urban and rural settings. By understanding their diversity and spread, combining with people' use and access, we aim to inform effective health policies and interventions, crucial for combating antimicrobial resistance (AMR) in low- and middle-income countries. 

Dr Suparna Mitra, Senior Lecturer in Bioinformatics and Data Science (Microbiomics),

Leeds Institute of Medical Research

Michael Beverley Innovation Fellow 

Horizons Institute Global Crucible Member.   

University of Leeds, United Kingdom

 Antimicrobial resistance (AMR) is a major global problem, causing millions of deaths each year, including a significant number in Bangladesh. A recent report from Bangabandhu Sheikh Mujib Medical University highlighted the ineffectiveness of 36 antibiotics, leading over 26,000 deaths during Jan'22-Jun'23. However, this data only reflects hospital cases, and the true extent of the issue remains unclear. It's crucial to recognize the dangers of widespread antibiotic use, particularly in low- and middle-income countries where access to these drugs is widespread.

Our goal is to address AMR on a global scale by focusing on its prevalence outside of hospitals. We aim to understand how antimicrobials are used in the general population (AMA, AMQ, AMU), how AMR spreads through food and the environment, and its impact on communities. Through qualitative questionnaires and advanced genetic sequencing techniques like Whole genome shotgun sequencing (WGSS), we will analyse microbial composition, AMR gene content, and genetic diversity in over 2000 samples. This approach will help us understand how AMR genes move, evolve, and contribute to the transmission of pathogens. By combining this data with health information and surveys, we aim to provide policymakers with evidence-based recommendations to combat AMR effectively. 

Our proposed pilot study in Bangladesh aims to uncover key drivers of AMR by identifying antimicrobial usage and prevalent AMR genes in diverse locations (urban, peri-urban, rural). Our One Health approach examines AMR gene dynamics under varying antibiotic exposure, offering insights into Diversity, Distribution, and Dissemination. The study benefits three stakeholders:

The communities: We will study people in each community to grasp their living conditions, environment, and antibiotic use, with a focus on understanding AMR prevalence. Drawing insights from rural communities, we aim to encourage adopting traditional diets for common illnesses in urban areas, reducing reliance on antibiotics.

The drug developers: knowing where resistance stems from could enable the development of more effective therapeutic combinations.

Policymakers:  Our solution caters to health protection organisations, offering vital insights into AMR spread and microbiome diversity for strategic interventions. Early engagement with policymakers ensures our findings directly influence impactful measures, safeguarding public health. knowing what AMR are most prevalent indicates which antimicrobials are being over-prescribed to enable a campaign to reduce their consumption.

Ultimately, this is all aimed at reducing the health burden and this pilot study can be translated in other locations in Bangladesh and in other LMICs.

The proposed project offers a significant public good by addressing critical gaps in our understanding of antimicrobial resistance (AMR) in low- and middle-income countries (LMICs). The application of shotgun metagenomics will provide comprehensive insights into the spread of AMR across clinical, environmental, and animal settings, fostering a holistic One Health approach.

Firstly, the project contributes to the public good by enhancing community-level data collection in LMICs, filling a major gap in current knowledge. By assessing AMR in diverse environments and species, the initiative goes beyond the conventional high-income country focus, leading to a more inclusive and representative understanding of the problem.

Secondly, the proposed genomics approach enables the development of accurate estimates of bacterial disease and AMR burden, essential for informed policymaking. This empowers public health officials and policymakers with evidence-based insights to implement more effective policies and actions against AMR.

Ultimately, the project promotes global public health and security by addressing a critical aspect of the One Health crisis. The data generated and policies informed by this research have the potential to save lives, reduce healthcare costs, and contribute to sustainable development, making it a valuable public good with far-reaching implications. 

Future goal: Modulating the microbiome using probiotics.

This project will create tangible impact by providing actionable insights into AMR across in LMICs, focusing on Bangladesh as a pilot. 

Stakeholders include:

People: Community engagement aims to foster knowledge about responsible antibiotic usage while emphasising the significance of incorporating traditional probiotic foods into daily living for improved health by tapping into rural wisdom to encourage lifestyle changes, reducing reliance on antimicrobials, and enhancing community well-being.

Public Health Authorities: Comprehensive data empowers authorities for targeted interventions, improving bacterial disease management, and curbing AMR spread, thus safeguarding community health and reducing healthcare system burden.

Clinicians: Accurate AMR prevalence information aids informed treatment decisions, ensuring effective antimicrobial use, minimizing treatment failure risks, and improving patient outcomes.

Researchers and Policymakers: Project findings offer evidence-based policies, guiding strategies for antimicrobial stewardship, surveillance, and public awareness campaigns to combat AMR effectively.

Livestock and Agricultural Sector: Assessing AMR in animals/environment supports biosafety strategies for farms, ensuring animal health, and addressing concerns about food safety and security.

Preparations are in progress to implement a comparable study framework in Africa, collaborating with Ghana and Pretoria, supported by UoL’s Global Crucible Program (Horizons Institute). Dr. Mitra’s visit in Ghana in June’23 was a key component of this endeavour.

After completion, to scale our project, strategic approach will focus on dissemination, collaboration, and sustainability.

Dissemination and Advocacy: In the first year, the emphasis will be on widely disseminating the research findings through scientific publications, conferences, and engagement with local and international stakeholders. This creates awareness and builds advocacy for evidence-based policies against AMR.

Capacity Building: Over the next three years, the project will invest in capacity-building initiatives within LMICs. Training local researchers, healthcare professionals, and policymakers in genomics and AMR management ensures the sustainability of efforts beyond the project's timeline.

Collaborative Partnerships: Forming partnerships with local and global organisations will be a key strategy. This includes NGOs, Probiotic companies, other countries (e.g. we have already started collaboration discussion with Ghana, South Africa, India) and policy leaders.

Policy Integration: Actively engaging with policymakers will ensure the integration of research outcomes into national and regional AMR action plans. Establishing the project as a valuable resource for policy development enhances the likelihood of sustained impact.

Continuous Surveillance: Implementing a system for continuous surveillance of AMR patterns allows for ongoing monitoring and adaptation of strategies. This ensures that the project's impact remains relevant and effective over the next three years and beyond.

The project's success will be evaluated against key impact goals, using a blend of quantitative and qualitative assessments.

Data Quality and Quantity:

The success of the project relies heavily on the comprehensive and accurate metagenomic data collected from human, environmental, and animal samples. Our goal is to obtain 5GB of paired-end shotgun metagenomic data from all samples (3517), ensuring both quality and quantity.

Policy Implementation:

The project endeavours to shape policies and actions to combat AMR. Success will be measured by the adoption and implementation of evidence-based policies derived from research findings, leading to tangible enhancements in AMR management and control.

Health Outcomes:

The project's effectiveness will be gauged by its positive impact on public health, specifically in terms of diminishing bacterial diseases. Monitoring health outcomes within the target population will provide a direct measure of the intervention's success.

Stakeholder Engagement:

Success will be determined by the continuous depth of engagement and collaboration with local communities, public health authorities, clinicians, and policymakers to bring about meaningful change.

Sustainability:

The continuity of positive results from developed policies and practices beyond the project duration will signify a successful and sustainable approach to combating AMR in LMICs.

Our ambitious, community-based plan could be subjected to potential bottlenecks for which we outline our contingency plans below:

In 2023, we prioritised community understanding for project success. Our research assistants played a vital role in building trust, connecting with individuals, and gathering insights on daily routines, responses to illness, and medication access, particularly addressing concerns about antimicrobial limitations.

Regulatory and Ethical Considerations: Stringent regulatory frameworks and ethical considerations have the potential to impede research progress. The project team has successfully navigated this path, securing ethical approval for the proof-of-concept study with human participants from the Bangladesh Medical Research Council (BMRC), ensuring compliance. This experience will aid in expediting future approvals for the broader project, including the necessary approvals for human and animal samples.

Limited Stakeholder Engagement: Inadequate engagement with local communities, healthcare professionals, and policymakers may hinder the adoption of research findings. The project will implement targeted communication strategies, emphasising the importance of collaboration and knowledge exchange.

Short-term Focus: While initial involvement is often enthusiastic, there's a potential for subsequent decline. To counter this, we recognize the significance of hosting regular engagement events and sharing project results with stakeholders. This ensures they see the progress stemming from their dedicated efforts.

With extensive research experience in Germany, the UK, and Singapore, I possess skills to drive culturally-informed research-based change. Born in India, I understand the challenges, like unrestricted access to antimicrobials, prevalent in many LMICs, resulting in ineffective treatments and AMR.

Passionate about addressing AMR in LMICs, I initiated a proof-of-concept study in Dhaka's Sher-e-Bangla Nagar slum, exploring the impact of unrestricted antimicrobial use on the gut microbiome and ARGs. Observing the living conditions in Dhaka prompted expanding our project to address not only human consumption but also indirect exposure through food and the environment in underprivileged communities.

Financial constraints challenge sampling in various locations and getting community level data. The Trinity Challenge is crucial for overcoming these obstacles, offering resources for comprehensive global AMR research. Recruiting and training local researchers is key to our solution for truthful information gathering. Funds are critical to achieving this in multiple locations.

With >14 years of experience in data science, mathematics, and medical/environmental research, my interdisciplinary perspective aligns with The Trinity Challenge's mission. My unwavering commitment to mitigating AMR in LMICs would greatly benefit from their support, enhancing the success and reach of my vital research.

We had a positive discussion with Optibiotix, a Yorkshire-based pharmaceutical company developing technologies that modulate the human microbiome. Following the positive dialogue, we plan to involve Optibiotix in ongoing discussions.

We also aim to expand discussions with other probiotics companies like BetterVits, Health Plus, Benecol, and ProBio Max, including local ones.

We are engaging with Horizon’s Institute’s Global Biosphere Sensing Network, and IIT Madras’s Biosensor’s laboratory for microorganism detection. Dr. Mitra, a BSAC award recipient for previous Covid project, will sought for extended collaboration on this specific initiative.

To ensure international support, we plan to involve the UK’s Consulate in Bangladesh and leverage UoL's strong ties with the UK government. Collaborations with Indian Council of Medical Research and South African Medical Research Council are intended to expand the project globally.

Further, partnerships with Ineos Oxford Institute, Imperial College, Facebook, Google (Health), Amazon Web Services, McKinsey&Company, Patrick J.McGovern Foundation, and philanthropic giants like Bill & Melinda Gates Foundation, Clinton Health Access Initiative, Tony Blair Institute, Black Sands aim to diversify support and resources.

Additionally, we seek collaboration with the Global Virome Project to synergize viromic data and contribute to their initiative in identifying zoonotic viral threats to prevent future pandemics.