A multi-state occupancy modelling framework for robust estimation of disease prevalence in multi-tissue disease systems.
Abstract
1. Given the public health, economic and conservation implications of zoonotic diseases, their effective surveillance is of paramount importance. The traditional approach to estimating pathogen prevalence as the proportion of infected individuals in the population is biased because it fails to account for imperfect detection. A statistically robust way to reduce bias in prevalence estimates is to obtain repeated samples (or sample many tissues in multi-tissue disease systems) and to apply statistical methods that account for imperfect detection and permit the interdependence of the infection process across multiple tissues. 2. We developed a multi-state occupancy modelling framework which considers two scenarios about the infection process, one where no assumptions about the dependencies among the tissues are made (general), and another where dependence among tissues is not permitted (constrained). 3. We applied this framework to pseudorabies virus (PrV) DNA detection data obtained from whole blood; and oral, nasal and genital mucosa of 510 feral swine Sus scrofa during the years 2014-2016 in Florida, USA. 4. The constrained model was better supported by data. 5. PrV prevalence estimates varied among tissues and were higher than the naïve estimates, ranging from to 0.06 (CI: 0.02-0.14) in genital to 0.54 (CI: 0.14 0.82) in nasal tissue. Probability of PrV detection ranged from 0.11 (CI: 0.06-0.18) in nasal to 0.51 (CI: 0.21-0.81) in genital tissue. PrV prevalence was not affected by the age or sex of the animal or the year of sampling, but prevalence increased as drought severity increased. 6. The conditional probability of detecting PrV given infection in at least one tissue type within an individual was highest for nasal tissue, suggesting that nasal is the best tissue to sample for PrV surveillance if only one tissue can be sampled, at least for systems with tissue-specific prevalence and detection probabilities similar to ours. 7. Synthesis and applications. We focused on inferences about pathogen prevalence in multi-tissue disease systems, dealing with both nondetection and potential dependencies among tissues in infection status. We found strong evidence of variation in both prevalence and detection probabilities among tissues. Our results emphasize the importance of sampling multiple tissues and of applying inference methods that account for imperfect detection in the surveillance of systemic diseases. The multi-state modelling framework is broadly applicable to the surveillance of pathogens that infect multiple tissues and can be used even when the infection status of the pathogen in one tissue may depend on the infection status of the pathogen in other tissue(s).