EpiFusion: Joint inference of the effective reproduction number by integrating phylodynamic and epidemiological modelling with particle filtering

Accurately estimating the effective reproduction number (Rt) of a circulating pathogen is a fundamental challenge in the study of infectious disease. The fields of epidemiology and pathogen phylodynamics both share this goal, but to date, methodologies and data employed by each remain largely distinct. Here we present EpiFusion: a joint approach that can be used to harness the complementary strengths of each field to improve estimation of outbreak dynamics for large and poorly sampled epidemics, such as arboviral or respiratory virus outbreaks, and validate it for retrospective analysis. We propose a model of Rt that estimates outbreak trajectories conditional upon both phylodynamic (time-scaled trees estimated from genetic sequences) and epidemiological (case incidence) data. We simulate stochastic outbreak trajectories that are weighted according to epidemiological and phylodynamic observation models and fit using particle Markov Chain Monte Carlo. To assess performance, we test EpiFusion on simulated outbreaks in which transmission and/or surveillance rapidly changes and find that using EpiFusion to combine epidemiological and phylodynamic data maintains accuracy and increases certainty in trajectory and Rt estimates, compared to when each data type is used alone. We benchmark EpiFusion's performance against existing methods to estimate Rt and demonstrate advances in speed and accuracy. Importantly, our approach scales efficiently with dataset size. Finally, we apply our model to estimate Rt during the 2014 Ebola outbreak in Sierra Leone. EpiFusion is designed to accommodate future extensions that will improve its utility, such as explicitly modelling population structure, accommodations for phylogenetic uncertainty, and the ability to weight the contributions of genomic or case incidence to the inference.