Estimation of temporal covariances in pathogen dynamics using Bayesian multivariate autoregressive models

It is well recognised that animal and plant pathogens form complex ecological communities of interacting organisms within their hosts, and there is growing interest in the health implications of such pathogen interactions. Although community ecology approaches have been used to identify pathogen interactions at the within-host scale, methodologies enabling robust identification of interactions from population-scale data such as that available from health authorities are lacking. To address this gap, we developed a statistical framework that jointly identifies interactions between multiple viruses from contemporaneous non-stationary infection time series. Our conceptual approach is derived from a Bayesian multivariate disease mapping framework. Importantly, our approach captures within- and between-year dependencies in infection risk while controlling for confounding factors such as seasonality, demographics and infection frequencies, allowing genuine pathogen interactions to be distinguished from simple correlations. We validated our framework using a broad range of synthetic data. We then applied it to diagnostic data available for five respiratory viruses co-circulating in a major urban population between 2005 and 2013: adenovirus, human coronavirus, human metapneumovirus, influenza B virus and respiratory syncytial virus. We found positive and negative covariances indicative of epidemiological interactions among specific virus pairs. This statistical framework enables a community ecology perspective to be applied to infectious disease epidemiology with important utility for public health planning and preparedness. Author summary Disease-causing microorganisms, including viruses, bacteria, protozoa and fungi, form complex communities within animals and plants. These microorganisms can coexist harmoniously or even beneficially, or they may competitively interact for host resources. Well-studied examples include interactions between viruses and bacteria in the respiratory tract. Whilst ecological studies have revealed that some pathogens do interact within their hosts, identifying interactions from available population scale data from health authorities is challenging. This is exacerbated by a lack of large-scale data describing the infection patterns of multiple pathogens within single populations over long time frames. Furthermore, methods for evaluating whether infection frequencies of different pathogens fluctuate together or not over time cannot readily account for alternative explanations. For example, human pathogens may have related seasonal patterns depending on the age groups they infect and the weather conditions they survive in, and not because they are interacting. We developed a robust statistical framework to identify pathogen-pathogen interactions from population scale diagnostic data. This framework serves as a crucial step in identifying such important interactions and will guide new studies to elucidate their underpinning mechanisms. This will have important consequences for public health preparedness and the design of effective disease control interventions.