A Systematic Review and Guide for Using Multi-response Statistical Models in Co-infection Research

The simultaneous infection of organisms with two or more co-occurring pathogens, otherwise known as co-infections, concomitant infections or multiple infections, plays a significant role in the dynamics and consequences of infectious diseases in both humans and animals. To understand co-infections, ecologists and epidemiologists rely on models capable of accommodating multiple response variables. However, given the diversity of available approaches, choosing a model that is suitable for drawing meaningful conclusions from observational data is not a straightforward task. To provide clearer guidance for statistical model use in co-infection research, we conducted a systematic review to (i) understand the breadth of study goals and host-pathogen systems being pursued with multi-response models and (ii) determine the degree of crossover of knowledge among disciplines. In total, we identified 69 peer-reviewed primary studies that jointly measured infection patterns with two or more pathogens of humans or animals in natural environments. We found stark divisions in research objectives and methods among different disciplines, suggesting that cross-disciplinary insights into co-infection patterns and processes for different human and animal contexts are currently limited. Citation network analysis also revealed limited knowledge exchange between ecology and epidemiology. These findings collectively highlight the need for greater interdisciplinary collaboration for improving disease management.