Drivers_of_antimicrobial_resistance_in_Uganda_and_Malawi_3

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 is the spatio-temporal flux of ESBL- E. coli and K. pneumoniae between humans, animals and the environment? How do the mechanisms of ESBL observed in human clinical samples relate to those in their environment? Methods: Human and animal stool and environmental samples have been longitudinally collected from 400 households in urban, peri-urban and rural settings in Malawi and Uganda. Shotgun metagenomic sequencing will be performed on 416 human and environmental samples from randonly selected 52 households, with each household providing samples at two time points. Expected findings The study will help us understand the AMR gene burden, diversity and contamination in the environment, household and community as well as carriage within healthy and ill humans or animals. Combined, we will use these data to understand spread of ESBL E. coli/K. pneumoniae in areas with different human and animal population densities with different levels of affluence and infrastructure.