Drivers_of_antimicrobial_resistance_in_Uganda_and_Malawi__DRUM_

In Low and Middle Income countries (LMICs), there is a high incidence of severe bacterial infection, a critically inadequate health system infrastructure to diagnose and treat bacterial infections and widespread and uncontrolled availability of antimicrobials . This situation causes both a huge burden of morbidity and mortality and is increasing selective pressure for the emergence of AMR in pathogens. In many LMICs, extended spectrum betalactamase (ESBL) producing infections are locally untreatable, due to unavailability of carbapenems or other reserve antibiotics. The mechanisms that support the emergence, movement, and persistence of antimicrobials within communities are poorly understood both qualitatively and quantitatively. This makes it difficult to identify or predict the impact of intervention strategies. DRUM will characterise the emergence and spread of AMR within complex social settings in Malawi and Uganda using an agent-based modelling approach. Specifically, we will answer the following three core research questions: What are the drivers of ESBL E. coli and ESBL Klebsiella pneumoniae transmission in Uganda and Malawi? What are the critical points at which efforts to interrupt human AMR acquisition are likely to have the greatest impact? Which strategies are likely to be most affordable and feasible to societies and how far is this specific to context? Methods: We will recruit 400 households in urban, peri-urban and rural settings in Malawi and Uganda. Each household will undergo human and animal stool, and environmental sampling for ESBL E. coli and ESBL Klebsiella pneumoniae, which will be sequenced at the Wellcome Sanger Instittute. WASH behavioural practices and antibiotic usage data will be incorporated with the microbiological and genomic data to generate an agent-based model determining critical points at which efforts to interrupt human AMR acquisition are likely to have the greatest impact. Expected findings Through the creation of an agent-based model, DRUM intends to determine the drivers of ESBL E. coli and ESBL Klebsiella pneumoniae transmission in Malawi and Uganda. We aim to establish the DRUM study sites as sustainable model settings for interdisciplinary study and mitigation of AMR by embedding a One Health strategy at the heart of a project, that will generate outputs applicable to similar communities throughout East and Southern Africa, and beyond.