Revolutionizing AMR Surveillance (RAMS study)

Our pipeline empowers public health institutions with precise genomic analysis, tracking MDRO transmission. We standardize sample collection, sequencing, and analysis, in a resource-limited setting creating an open-access dashboard showcasing trends, aiding interventions. Cost-benefit analysis validates efficacy, while extending surveillance to food chains for comprehensive AMR control.

Dr John Mambwe Tembo Scientific Coordinator HerpeZ Zambia

Urgent Need for Antimicrobial Resistance (AMR) Surveillance in Africa

Antimicrobial resistance (AMR) poses a significant threat to public health in Africa, according to Rand study AMR will cause approximately 10 million deaths per year by 2050 with 4 million of those deaths occuring in Africa. This situation necessitates immediate attention and concerted efforts. Factors such as the misuse of antimicrobial drugs, including falsified or substandard medicines, inappropriate antibiotic use, and agricultural practices, contribute to the escalation of AMR across the continent.

Inadequate surveillance data impedes efforts to understand and address AMR effectively, leading to challenges in developing public health policy, interventions and patient care guidelines, which leads ing to poor treatment outcomes. 

The consequences of AMR are dire, with implications across various infectious syndromes, including urinary tract infections, bloodstream infections, pneumonia and diarrheal diseases resulting in increased morbidity and mortality, further burdening healthcare systems already strained by limited resources.

Addressing the urgent need for AMR surveillance in Africa is paramount to safeguarding public health, reducing the burden of infectious diseases, and preserving the effectiveness of antimicrobial drugs for future generations.

There are multiple stakeholders who will benefit from this pipeline and it will be vital to engage from the start to ensure by-in throughout the project. Primarily, our pipeline will serve members of the community at risk of infection with an MDRO, as highlighting high risk connections will enable targeted interventions and thus reduce the risk of MDRO transmission. To understand community needs, we will engage with members of the public from the beginning, to ascertain what data they feel is relevant and developing the dashboard for ease-of-use. We will do this by running regular focus groups with e.g. patients and farmers.

We will also engage with healthcare providers, including veterinary and clinical healthcare workers, prescribers, laboratory staff and policy makers. These groups are vital for the initial technical needs analysis, risk assessment, cost benefit analysis and dashboard development, as well as continual optimisation. We will engage with these stakeholders using focus groups, knowledge, attitudes and practices studies and trial runs of the dashboard. We have strong connections with clinical (Royal Free Hospital, UK and University Teaching Hospital, Zambia) and veterinary (UNZA veterinary school, Zambia), policy (Zambia National Public Health Institute (ZNPHI)) and standardisation (National Measurement Laboratory (UK)) stakeholders. 

Our genomic AMR surveillance pipeline and open access, free to use dashboard will provide all stakeholders with access to data on the rates of AMR in MDROs within Zambia, where transmission is occurring and the connections with transmission risks. In conjunction with policy makers, this will lead to targeted interventions, and a reduction in MDRO transmission between humans, animals and the environment.

At a public health/research level, all of the methodologies will be open source, so other laboratory staff, healthcare workers, public health staff. may access our protocols to apply them within their own settings, collect their own data and include it in the database, increasing available data. 

All manuscripts resulting from the project will also be open access. This will increase the relevance and implementation of the pipeline into more settings/countries, further spreading the potential for MDRO transmission reduction.

Our public engagement work will ensure we disseminate the benefits of our pipeline and the results that it generates, helping to improve understanding of AMR and the risk factors amongst those who participated in our research, as well as other members of the community.

Our pipeline will create impacts for multiple target populations and stakeholders:

·   Patient/animal health and the community: Our primary motivation for the development of this pipeline is to reduce the health burden of MDROs. Identifying risk factors will enable the implementation of targeted interventions, leading to reduced MDRO transmission, and antibiotic

use. Our public engagement work will gain the pipeline a wider audience, ensuring that it is accessible to those who ultimately funded it.

·  Public health policymakers: Our pipeline will enable public healthcare stakeholders can identify best practices, targeted interventions, behavioural changes and infection prevention and control policies to reduce the burden of AMR and MDROs in Zambia. Making it a One Health tool will promote cooperation between human, environmental and animal health stakeholders. A cost benefit analysis of the pipeline, and involving policy makers throughout, will ensure the pipeline provides not only health benefits, but economic and policy ones too. 

·  Capacity development: The successful optimisation and validation of the pipeline, open access publication of data and online dissemination of resources will lead to the utilisation of the pipeline by other research groups in other countries, improving capacity across LMICs and improving AMR surveillance.

Once the pipeline is standardised for AMR surveillance for hospitals in Zambia, we aim to further develop it to cover other AMR and One Health settings, such as the food chain and aquaculture, and translate it for use in more LMIC countries. We have ongoing studies looking at antibiotics in meat in the food chain, which we aim to link this genomic project with, and will apply for further funding to explore this development.

The dashboard will be further developed to include features for all One Health settings. Machine learning will be optimised to ensure that the links and analyses from accumulating genomic, geospatial and risk factor data will feed back into the more accurate understanding of these associations.

We anticipate that there will be uptake of the tool by researchers in other countries and in other capacities. We aim to ensure the tool is translatable to these settings, and once established in Zambia we will disseminate the results from our surveillance data, showcasing to others (including researchers, policy makers and antimicrobial stewardship actors). Our data will form baseline evidence to inform public health policy, and ultimately reduce the risk of AMR transmission and burden in humans and animals.

We will measure impact by collecting data from clinical staff on turnaround time of AMR results and whether results from surveillance are being used to inform on patient care and antimicrobial stewardship policies both within the healthcare facilities and on a national policy level working with the National Public Health Institute.

Patient/animal health and the community:

·   Measuring the reduction in rate of MRDOs seen in hospital patients (using data collected during this study, and afterwards)

·   Measuring the rate of antibiotic use (using data collected during this study, and afterwards)

Public health policymakers:

·  The number of targeted interventions implemented as a result of our baseline data

·   The results of the cost-benefit analysis will identify whether the pipeline is cost effective, and money can be saved by its implementation

Scientific and capacity development:

·   The number of open access manuscripts and online resources derived from this project

·   The number of interactions with research/public health groups in Zambia and other countries

·   The number of sites beginning to establish the pipeline in their own areas

·   The number of conferences/meetings attended

·   The number of further grants/collaborations applied for as a result of this project

The main barriers will be lack of infrastructure in some of the rural laboratories to conduct culture and next generation sequencing experiments. However ONT technology is perfect for these settings as setup costs are low and various ONT platforms can run on minimal internet connectivity and demands on electricity. 

One of the other barriers is having laboratory technicians skilled in the use of next generation sequencing. We have previously run workshops in Zambia on whole genome sequencing and  setup of next generation sequencing laboratory and so we envision being able to do this again to build up the critical capacity required for roll out of this technology in the healthcare systems of LMICs and in the case particularly in Zambia with our already proven track record. We will also deploy hub and spoke method working with National Public Health institute to optimise sample transportation network built off the backbone of the TB sample referral program for AMR surveillance.

We are seeking a grant to support the development of a cost-effective Antimicrobial Resistance (AMR) pipeline featuring an integrated dashboard for comprehensive historical, geospatial, and risk factor analysis of AMR. The Trinity Challenge presents a unique opportunity to expedite the advancement of our solution, making it applicable in practical settings and adaptable to resource-limited environments. This initiative aims to influence AMR stewardship policies within healthcare systems facing resource constraints. The funding provided will facilitate the transformation of our pipeline and dashboard into a format suitable for deployment in Low- and Middle-Income Countries (LMICs), prioritizing communities severely affected by AMR.

Our pipeline's core principle closely aligns with the Trinity Challenge's emphasis on practical solutions and data-driven impact in healthcare. We are confident that our approach, utilizing data from whole genome sequencing to offer critical insights into AMR transmission and control, is innovative and aligns well with the goals of this challenge.

A major obstacle in the deployment of surveillance tools is securing the resources necessary for initial implementation to demonstrate proof of concept. Thus, we are turning to the Trinity Challenge for support.Through this partnership, we aim to overcome barriers and propel our AMR pipeline towards meaningful, scalable impact in LMICs.

Our pipeline when implemented is sure to generate alot of data. We would be looking to partners particularly experienced in the use and analysis of large datasets like the one we would generate to hopefully get additional insights and uses and analysis of the data generated.