AMR Wastewater-Based Surveillance (WWBS) Project in Uganda

Uganda has poorly regulated use of antimicrobials and suboptimal AMR surveillance leading to increased AMR prevalence and morbidity. AMR surveillance data is key to mitigation. Our solution will establish a National AMR WWBS system to monitor trends and emerging resistances. Data obtained will inform measures to curb AMR.

Moses Joloba, Professor of Molecular Biology, CEO of Makerere University Biomedical Research Centre. Pioneered the TB National sample referral systems, Director of the Epidemics Lab that conducts COVID-19 WBBS.

AMR is a global challenge; it claimed nearly 1.3 million lives in 2019, comparable to TB and above HIV and Malaria. One in five occurred among children under 5. In Uganda in 2019, 7,100 deaths were attributed directly to AMR and 30,700 deaths associated with AMR. This is higher than deaths due to respiratory infections, tuberculosis, cardiovascular diseases, neglected tropical diseases, and malaria. 

Major causes of AMR in Uganda are poorly regulated use and quality of antimicrobials and suboptimal AMR surveillance relying on traditional phenotypic laboratory testing of clinical cases. This AMR surveillance approach has limitations: (1) only 6 active Public Health labs have drug susceptibility testing (DST) capacity for a population of 50 million;  (2) reliance on community health-seeking behaviour for samples;  and (3) fragmented information reporting system with suboptimal aggregation of testing data. The AMR WWBS Solution is designed to establish a cost-effective, near real-time, countrywide AMR surveillance system that is based on non-clinical samples. Data obtained from routine AMR WWBS will be used for Public Health Action that will inform novel strategies for mitigation.

Our solution targets policymakers and healthcare workers in Uganda, with a specific focus on benefiting pregnant individuals, neonates/infants, trauma and post-operative patients, who bear a disproportionate burden of Antimicrobial Resistance (AMR). We shall conduct baseline and follow-up assessments to understand the factors responsible for the growing AMR burden in these target populations. Our Solution will generate data that will inform public health interventions that will address AMR in these vulnerable groups. To ensure that proposed interventions are appropriate to the needs of the target audience, we will actively engage key stakeholders such as the Ministry of Health, Community Health Workers and the Target Population to ascertain the feasibility of proposed interventions, modifications will be done accordingly.

National AMR Guidelines:

The solution aims to contribute to the development of AMR WWBS guidelines & inform the review of National AMR guidelines which are due for update. These guidelines will optimize the use of antimicrobial drugs, promote public awareness, and strengthen evidence-based practices, thereby minimizing resistance.

AMR-WWBS NGS Dashboard and Repositories:

The AMR-WWBS NGS Dashboard and AMR profile repositories will offer open and easy access to accurate information about national AMR surveillance data. This promotes transparency and knowledge sharing within the global community.

Report/Booklet and Map of Uganda with Resistance Patterns:

The creation of a report/booklet and map of Uganda displaying resistance patterns for different regions will provide valuable insights. The publication will target the Ugandan Ministry of Health, hospital systems, and the general public, fostering awareness and understanding of AMR.

Policy Briefs:

The generation of policy briefs will support policy-making bodies with accurate and representative AMR data. This will guide the formulation of policies aimed at regulating antimicrobial drug use effectively.

Strengthened National AMR Surveillance System:

The establishment of a strengthened national AMR WWBS surveillance system will augment the suboptimal AMR Clinical Surveillance and hence strengthen AMR surveillance

The solution will create a robust and cost-effective AMR WWBS surveillance system.  The logical links between our activities, outputs, and expected outcomes are as follows:

Implementing WWBS using Next-Generation Sequencing (NGS) technology for nationally representative wastewater samples will generate reliable and comprehensive data on AMR trends and emerging resistances that will inform policy development and updates on antimicrobial drug use.

Implementation of informed policies to mitigate the burden of AMR, specifically targeting vulnerable populations such as neonates, pregnant individuals, trauma, and post-surgical patients. The overall impact is expected to result in a decrease in mortality among the identified key populations due to optimized antimicrobial drug use and enhanced AMR prevention and control efforts.

The logical progression from surveillance to policy formulation and implementation is based on evidence from successful wastewater surveillance for COVID-19 in Kampala where the Ministry of Health has relied on our results to develop National COVID-19 testing guidelines that include a component of WWBS (see uploaded results). By directly influencing policy guidelines and subsequently optimizing antimicrobial drug use, our solution aims to create a tangible and measurable impact, ultimately saving lives and improving the well-being of the Ugandan population.

Baseline data: By the end of year one, all 17 regional referral hospitals and associated communities hence 34 facilities (that represent a countrywide coverage) will enrolled on WWBS. For the first time, a new data source on sub-national AMR WWBS data will be availed to the MoH Surveillance dept for Public Health action. This data will be used by MoH to design regionally contextualized Public Health interventions. A baseline sub-regional KAPs assessment will also be done.

Best Practices & Trend Analysis: From the second year, routine (monthly) reports on a trend analysis of AMR resistance patterns, and comparison with any available AMR Clinical Data with be availed to MoH & communities to monitor trends & performance of sub-regionally contextualized Public Health interventions. Best practices shall be noted and scaled up. Regional interventions provide an opportunity for peer-to-peer learning mechanisms & benchmarking.

Adaptation: Towards the end of the third year, the AMR WWBS findings will be disseminated to MoH & Community Health Workers. These findings will inform the update of National AMR guidelines, development of AMR WWBS Guidelines and their dissemination.  Using baseline data on KAPs, we shall measure the impact of our intervention.

In the first year, our main measure of success will be the establishment of active reporting for 34 WWBS sites (17 Regional Referral Hospitals and 17 communities). This will provide baseline regional AMR profiles, and we will also collect baseline sub-regional Knowledge Attitude Practices (KAP) data.

From the second year, we will analyze measurement trends in AMR resistance profiles, KAPs, and will identify best practices. 

At the end of the third year, we will measure the extent of the adoption of our findings into national guidelines and practices.

Deficient Comparable Clinical AMR Data: The lack of sufficient comparable clinical AMR data poses a challenge to trend and biomarker analysis. 

Loss of Moore Swabs Due to Environmental Factors: Environmental factors, such as heavy rains, may lead to the loss of Moore Swabs. To mitigate this, our designs will accommodate potential losses.

Reception and Implementation of Generated Data: The successful reception and implementation of the generated data by stakeholders, including policymakers and antimicrobial prescribers, is crucial. We will engage in continuous dialogue, capacity-building efforts, and knowledge-sharing sessions to facilitate understanding and utilization of the data. 

Flooding: Flooding poses a risk to the implementation of WWBS. We plan to incorporate measures to address potential challenges posed by flooding, such as strategic site selection and the establishment of safeguards to protect equipment.

Technical Challenges in Fluid Normalization: Technical challenges, including the normalization of fluid, will be addressed through rigorous protocol development and validation.

 Sampling Bias and Regional Resistance Patterns: Technical challenges may arise from potential sampling bias and regional differences in resistance patterns. We will work closely with regional stakeholders, leverage local expertise, and continuously adapt our methods to ensure accurate representation and analysis of resistance patterns in the target environment.

We are applying to The Trinity Challenge to contribute to the establishment of a comprehensive solution to the growing antimicrobial resistance (AMR) crisis in Uganda. The barriers we face include poorly regulated antimicrobial use, suboptimal AMR surveillance, and limited data on the increasing burden. The Trinity Challenge can provide critical support in overcoming these barriers by offering the necessary funding to establish a countrywide AMR wastewater-based surveillance system. Leveraging our successful pilot of a COVID-19 wastewater surveillance system, combined with the expertise of collaborators and the existing sample transportation infrastructure, we can implement a robust solution. The funding will enable us to bring together expertise from various institutions, design effective protocols, and implement a nationwide initiative to monitor AMR trends and emerging resistance genotypes, contributing significantly to mitigating the impact of AMR in Uganda.

In a bid to ensure technical expertise and support for this solution, we wish to collaborate with Next-generation sequencing (NGS) experts such as Illumina and Sanger sequencing companies for WWBS protocol optimization, and Amazon Web Services for big data management and cloud storage capabilities.

Our solution would benefit from collaboration with potential funders who would support the adoption and sustainability of WWBS in Uganda and other African countries. We therefore wish to collaborate with the World Health Organization, the Bill & Melinda Gates Foundation, and Meta.

To ensure a One Health approach to this solution, we would also benefit from collaborations with organizations such as the Fleming Fund.