GenomicsDAM: Genomics informed Diarrheal disease and AMR Management

Diarrheal diseases and AMR are a major concern, globally and in Bangladesh, contributing to one in nine child deaths. Addressing this issue, the Bangladesh-UK “GenomicsDAM” solution aims to sequence bacterial genomes, personalise treatment, integrate data into geographic platforms, and implement targeted public health interventions in Dhaka, combating the AMR impact.

Taane G. Clark (Team lead; UK lead)

Dinesh Mondal (Team co-lead; Bangladesh lead)

Our project addresses the urgent issue of AMR, particularly in diagnosing and managing diarrheal diseases in Bangladesh. These infections, caused by bacterial pathogens (e.g., Escherichia coli), led to >250K recorded hospital cases in-country in 2022. Diarrheal diseases are the leading cause of mortality among children (<5 years), and globally account for 1 in 9 child deaths. In Bangladesh, the misuse of antibiotics and lack of precise diagnostic tools exacerbate this crisis, leading to ineffective treatment regimens, and rising healthcare costs. Our solution leverages cutting-edge whole-genome sequencing (WGS) technology and bioinformatic profiling tools to accurately detect AMR pathogens, offering a targeted approach to antibiotic prescription and enhancing the surveillance of resistance patterns. We will focus on diarrheal hospitals linked to icddr,b (Dhaka), which has an in-house sequencing facility supporting genomics-based investigations, but needs informatics-based analytics. We will develop a geographic information system (GIS) for mapping the WGS data and circulating AMR mutations. This GIS tool will provide critical insights into AMR pathogens and their geographical hotspots, launching further sampling in affected communities from environmental sources, as well as further sequencing to inform on AMR transmission. Our solution will provide crucial insights for infection control, supporting its roll-out nationwide/regionally.

Our solution serves healthcare providers, patients and communities affected by diarrheal diseases in Bangladesh, and researchers and clinicians at the icddr,b. By performing rapid and accurate detection of AMR pathogens through genome sequencing, our project directly addresses the urgent need for precise diagnosis and appropriate antibiotic treatment. This approach not only aids healthcare providers in prescribing the most effective treatments but also benefits patients by ensuring they receive the right antibiotics, reducing the risk of treatment failure and the spread of resistance. By identifying reservoirs of AMR pathogens in the community (e.g., contaminated meat and water), it will be possible to implement infection control measures to prevent transmission. Additionally, researchers at icddr,b, who play a crucial role in sample collection and sequencing, represent another key stakeholder. Our project aims to enhance their capacity to analyse WGS data, offering training workshops designed to empower researchers with the skills needed for advanced bioinformatic analysis. This initiative not only strengthens icddr,b's research and genomic-based investigation capabilities, but also enhances its contribution to global AMR surveillance and infection control strategies. Through these multifaceted engagements, our solution is crafted to meet the specific needs of each group, ensuring its effectiveness and applicability in real-world settings.

Our solution contributes to the public good by providing critical knowledge and data on AMR through an open-access, free-to-use GIS dashboard. This dashboard visualises the spread and trends of AMR pathogens in real-time, based on data generated from WGS/Amp-Seq of clinical/community samples collected in partnership with the icddr,b. The icddr,b are committed to solving public health problems facing Bangladesh and LMICs through innovative scientific research/solutions and their implementation by working with key stakeholders (e.g., Ministry of Health). The platform will serve as a valuable tool for researchers, healthcare providers, policymakers, and the public, offering insights into AMR dynamics that can inform infection control strategies, policy development, and public health interventions. In addition to the dashboard, we plan to disseminate our findings through peer-reviewed publications that will be freely accessible, ensuring that the knowledge generated from our work is available to the global community. By making our data and analyses available and open access, our solution supports a global effort to combat the AMR crisis, facilitating informed decision-making and fostering a collaborative approach to public health challenges. This commitment to sharing knowledge and tools exemplifies our dedication to contributing to the public good, enhancing the collective capacity to address AMR effectively.

Our solution, leveraging WGS and a GIS dashboard for AMR pathogen detection and tracking, will create tangible impacts for healthcare providers, patients, and researchers in Bangladesh, particularly those dealing with diarrheal diseases in under-served communities. The links between our activities - implementing WGS for AMR detection, developing a GIS dashboard for real-time tracking, and conducting training workshops for researchers/clinicians — and our expected outputs, include:

1. Enhanced diagnostic precision: By accurately identifying AMR pathogens, healthcare providers can prescribe effective antibiotics, reducing the misuse that contributes to resistance. This is expected to improve treatment outcomes for patients, particularly in vulnerable populations where access to healthcare is limited.

2. Informed public health: The GIS dashboard will visualise AMR spread, enabling policymakers and public-health officials to tailor infection control measures more effectively. This targeted approach can significantly mitigate the impact of AMR in under-served areas.

3. Strengthened capacity: Training icddr,b researchers/clinicians to analyse WGS data enriches local expertise, fostering a sustainable environment for ongoing AMR research/surveillance.

Evidence supporting our expected impact includes results from our TB-Profiler software, which has now been implemented globally in clinical settings and aids in integrating genomic data into clinical practice and improving personalisation of treatments. 

Over the next year, we plan to scale our impact by expanding the deployment of our WGS and GIS dashboard solution across a number of icddr,b linked healthcare facilities in Bangladesh. This includes enhancing data collection and analysis capabilities, refining our user-interface based on feedback from initial users, and increasing awareness through partnerships with public-health agencies. Our immediate goal is to establish a robust, evidence-based framework for AMR surveillance and response that can be adopted by other regions within the country.

In the next three years, we aim to extend our solution nationwide and within Asia, targeting countries with similar healthcare challenges and AMR patterns. By leveraging existing networks and collaborations with public health authorities, we will adapt our platform and training modules to suit diverse settings, emphasising low- and middle-income countries where AMR poses a significant threat. This scale-up strategy will be supported by continuous improvement of our technological tools, dissemination of knowledge through open-access publications, and active engagement in global health forums to share best practices and learnings. Our vision is to create a universally accessible, data-driven platform for AMR surveillance and management, contributing to global efforts to mitigate the AMR crisis and improve public health outcomes worldwide.

To monitor/evaluate the impact of our solution on AMR management, we have defined specific measurable indicators:

• Accuracy of AMR pathogen identification: We will compare the accuracy of our WGS technology against phenotypic tests performed (routinely) at icddr,b. This comparison will validate the effectiveness of WGS in accurately detecting AMR, aiming to match/exceed the reliability of conventional methods.
• Impact on antibiotic prescription practices: Through interviews with healthcare providers, we will assess how the implementation of our solution influences their antibiotic prescription decisions. Success will be measured by a reported increase in targeted antibiotic use, based on the precision diagnostics provided by our WGS-GIS approach.
• Capacity strengthening: A key goal is for analytics/interpretation of WGS data to be performed in-country. Progress towards this goal will be measured by the number of researchers/clinicians trained and the amount of data analysis conducted by local teams.

These indicators will measure the immediate outcomes of our solution, and its sustainable impact on strengthening local capacities for AMR surveillance/response. Success in these areas will indicate a significant advancement in both the management of AMR and the empowerment of local healthcare ecosystems, including through the proposed community sampling and identification of AMR transmission routes.

Our operational solution in Bangladesh aims to expand to other LMICs facing similar healthcare challenges and AMR patterns within 3 years. Our expansion strategy will be guided by specific contexts, considering infectious disease prevalence, existing healthcare infrastructure, and a commitment to addressing AMR.

Barriers and solutions:

• Technical/capacity: The specialised nature of bioinformatic analysis required for interpreting WGS data presents a hurdle in countries lacking in-country expertise. To address this, a core objective is capacity strengthening, involving training workshops and collaborative projects to enhance local skillsets.
• Infrastructure: Limited access to high-throughput sequencing technology and computational resources in LMICs poses an obstacle. We plan to collaborate with global health organisations, secure funding, and invest in infrastructure/training to support WGS data generation/analysis. The adoption of cost-effective and portable sequencing platforms, such as ONT, combined with high-throughput Amp-Seq assays, will be pivotal.
• Cultural/policy: Diverse cultural norms and policies regarding data sharing/privacy may complicate implementation. To navigate this, we will engage with local stakeholders early in the planning process, ensuring alignment with local norms and regulations to facilitate smoother implementation.

By strategically overcoming these challenges, our aim is to efficiently scale-up our solution, making a meaningful contribution to global initiatives combating AMR.

We are applying to The Trinity Challenge because we have an important solution to an AMR problem in diarrheal disease, which disproportionally impacts on child morbidity and causes high burden on healthcare systems, with resulting negative economic and societal impacts. The solution is leveraging advances in sequencing and informatician technologies, which are becoming routinely employed in UK healthcare and surveillance settings to personalise treatment and understand AMR transmission patterns. Our solution will strengthen capacity for genomics investigations and public-health decision making in Bangladesh, particularly across the sites linked to icddr,b. By the end of the project, we will be at a favorable stage for informing AMR policy, especially having directly engaged with specific stakeholder groups (e.g., Ministry of Health; National AMR Surveillance Initiative, Ministry of Environment, Forest and Climate Change; Food Safety Authority). The scale-up nationally requires governmental support, commercial laboratory and sequencing capacity, the involvement of AI/IT experts for big data storage/analysis, and potentially stakeholders in neighbouring countries to combine information (e.g., AMR mutation databases) and harmonise on regional solutions. The Trinity Challenge members/partners are working in these essential spaces. For example, the Tony Blair Institute is an advocate of pathogen sequencing, AI solutions, and works directly across governments.

We have expertise in developing sequencing-based solutions, and implementing them in pilot research projects to demonstrate their cost-effectiveness. We work with partners across Asia who are linked to government ministries (e.g., Thailand Ministry of Public Health, Philippines Department of Health), which are investing in genomics capacity (e.g., genome centres; embedding sequencing technologies in hospitals and clinics). We also work with the WHO and other stakeholders who are advocating sequencing-based diagnostics. However, the scaling-up of our solution requires experience in large-scale project management, expansive IT and data processing systems, and biomedical and commercial expertise. The Trinity Challenge partners have this expertise, and more, to provide sequencing-based solutions to improve global health.