Within-host priority effects and epidemic timing determine outbreak severity in coinfected populations

Coinfections of hosts by multiple pathogen species are ubiquitous, but predicting their impact on disease remains challenging. Interactions between coinfecting pathogens within hosts can alter pathogen transmission, with the impact on transmission typically dependent on the relative arrival order of pathogens within hosts (within-host priority effects). However, it is unclear how these within-host priority effects influence multi-pathogen epidemics, particularly when the arrival order of pathogens at the host population scale varies. Here we combined models and experiments with zooplankton and their naturally co-occurring fungal and bacterial pathogens to examine how within-host priority effects influence multi-pathogen epidemics. Epidemiological models parameterized with within-host priority effects measured at the single host scale predicted that advancing the start date of bacterial epidemics relative to fungal epidemics would decrease mean bacterial prevalence in a multi-pathogen setting, while models without within-host priority effects predicted the opposite effect. We tested these predictions with experimental multi-pathogen epidemics. Empirical dynamics matched predictions from the model including within-host priority effects, providing evidence that within-host priority effects influenced epidemic dynamics. Overall, within-host priority effects may be a key element of predicting multi-pathogen epidemic dynamics in the future, particularly as shifting disease phenology alters the order of infection within hosts.