Statistical Inference for Multi-Pathogen Systems

There is growing interest in understanding the nature and consequences of interactions among infectious agents. Pathogen interactions can be operational at different scales, either within a co-infected host or in host populations where they co-circulate, and can be either cooperative or competitive. The detection of interactions among pathogens has typically involved the study of synchrony in the oscillations of the protagonists, but as we show here, phase association provides an unreliable dynamical fingerprint for this task. We assess the capacity of a likelihood-based inference framework to accurately detect and quantify the presence and nature of pathogen interactions on the basis of realistic amounts and kinds of simulated data. We show that when epidemiological and demographic processes are well understood, noisy time series data can contain sufficient information to allow correct inference of interactions in multi-pathogen systems. The inference power is dependent on the strength and time-course of the underlying mechanism: stronger and longer-lasting interactions are more easily and more precisely quantified. We examine the limitations of our approach to stochastic temporal variation, under-reporting, and over-aggregation of data. We propose that likelihood shows promise as a basis for detection and quantification of the effects of pathogen interactions and the determination of their (competitive or cooperative) nature on the basis of population-level time-series data. Author Summary: It is becoming increasingly evident that pathogens associated with infectious diseases interact amongst themselves. Pathogen interactions can occur in a co-infected host, or in host populations where they co-circulate, and they can be cooperative or competitive. Four serotypes of dengue virus, for example, can exhibit both forms of interactions – cross protection for a temporary period and followed by long-lasting enhancement. This bears important consequences for understanding the ecology and developing control and prevention measures. Detecting such interactions in a natural host population, though, can be tricky. We show that studying the phase relation of epidemic cycles, as it has been typically done, is unreliable. We assess the ability of a likelihood based method in detecting such interactions, and find that they are accurate and robust. We propose that this framework shows promise of serving as a basis for detecting and quantifying pathogen interactions.