Antimicrobial resistance (AMR) is one of the greatest global health challenges of the 21st century, associated with increased morbidity and healthcare costs, prolonged illness, and nearly five million deaths per year. While AMR is commonly studied in a biomedical context, the evolution and dissemination of resistance is also driven by complex spatial, ecological, and social processes. Despite this, the spatial ecology of AMR transmission across humans, animals, and environments remains poorly understood. In addition, AMR is particularly understudied in low-income countries like Madagascar, which experiences an extremely high burden of AMR and many other factors that contribute to AMR and poor health, such as poor sanitation and hygiene measures, inaccessible healthcare, and food insecurity. Our study will investigate how human and animal mobility networks – framed within the context
of larger social, ecological, and spatial systems – drive AMR transmission in the SAVA Region of Madagascar. These findings will also increase understanding of AMR in other parts of the world, as many of the systemic inequities and challenges to health that influence AMR in Madagascar are likely to explain variation in AMR in other settings as well, including the United States.
Aim 1: Establish the prevalence and geographic distribution of three extended-spectrum β-lactamase (ESBL) AMR genes (TEM, SHV, and CTX-M) in rural agricultural Malagasy villages. To do so, we will use existing samples from 810 humans, 250 livestock, and 440 wild rodents from three villages in the SAVA Region (Sarahandrano, Mandena, and Andatsakala).
Aim 2: Identify demographic and socioeconomic factors that influence ESBL carriage. To do so, we will use previously collected survey data and quantify context-specific metrics of market integration based on household lifestyle, commercial goods ownership, crop sales, and vanilla growing. We hypothesize that these metrics of market integration are associated with increased likelihood of ESBL carriage due to increased economic access to antimicrobials and greater exposure to humans and animals that carry ESBLs.
Aim 3: Investigate the most important types of interactions for AMR transmission using social network and spatial data. We hypothesize that the more social contacts a human has – i.e., the higher their centrality in a social network – the more likely they are to carry an ESBL, as each contact provides an opportunity for direct ESBL transmission. This reflects the role of direct transmission of resistant microbes and genes in the dispersal of AMR, as well as the potential influence of shared antimicrobial use behaviors on social networks. We also hypothesize that the more environmental overlap a human or animal has with other individuals, the more likely they are to carry the same ESBLs. This captures the role of indirect transmission and common environmental AMR orntimicrobial exposures in AMR dispersal.