Practical unidentifiability of a simple vector-borne disease model: Implications for parameter estimation and intervention assessment.

Mathematical modeling has an extensive history in vector-borne disease epidemiology, and is increasingly used for prediction, intervention design, and understanding mechanisms. Many studies rely on parameter estimation to link models and data, and to tailor predictions and counterfactuals to specific settings. However, few studies have formally evaluated whether vector-borne disease models can properly estimate the parameters of interest given the constraints of a particular dataset. Identifiability analysis allows us to examine whether model parameters can be estimated uniquely-a lack of consideration of such issues can result in misleading or incorrect parameter estimates and model predictions. Here, we evaluate both structural (theoretical) and practical identifiability of a commonly used compartmental model of mosquito-borne disease, using the 2010 dengue epidemic in Taiwan as a case study. We show that while the model is structurally identifiable, it is practically unidentifiable under a range of human and mosquito time series measurement scenarios. In particular, the transmission parameters form a practically identifiable combination and thus cannot be estimated separately, potentially leading to incorrect predictions of the effects of interventions. However, in spite of the unidentifiability of the individual parameters, the basic reproduction number was successfully estimated across the unidentifiable parameter ranges. These identifiability issues can be resolved by directly measuring several additional human and mosquito life-cycle parameters both experimentally and in the field. While we only consider the simplest case for the model, we show that a commonly used model of vector-borne disease is unidentifiable from human and mosquito incidence data, making it difficult or impossible to estimate parameters or assess intervention strategies. This work illustrates the importance of examining identifiability when linking models with data to make predictions and inferences, and particularly highlights the importance of combining laboratory, field, and case data if we are to successfully estimate epidemiological and ecological parameters using models.