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The importation and subsequent establishment of novel pathogenic strains in a population is subject to a large degree of uncertainty due to the stochastic nature of the disease dynamics. Mathematical models need to take this stochasticity in the early phase of an outbreak in order to adequately capture the uncertainty in disease forecasts. We propose a general branching process model of disease spread that includes host-level heterogeneity, and that can be straightforwardly tailored to capture the salient aspects of a particular disease outbreak. We combine this with a model of case importation that occurs via an independent marked Poisson process. We use this framework to investigate the impact of different control strategies, particularly on the time to establishment of an invading, exogenous strain, using parameters taken from the literature for COVID-19 as an example. We also demonstrate how to combine our model with a deterministic approximation, such that longer term projections can be generated that still incorporate the uncertainty from the early growth phase of the epidemic. Our approach produces meaningful short- and medium-term projections of the course of a disease outbreak when model parameters are still uncertain and when stochasticity still has a large effect on the population dynamics.

Understanding the timing of the peak of a disease outbreak forms an important part of epidemic forecasting. In many cases, such information is essential for planning increased hospital bed demand and for designing of public health interventions. The time taken for an outbreak to become large is inherently stochastic, and therefore uncertain, but after a sufficient number of infections has been reached the subsequent dynamics can be modelled accurately using ordinary differential equations. Here, we present analytical and numerical methods for approximating the time at which a stochastic model of a disease outbreak reaches a large number of cases and for quantifying the uncertainty arising from demographic stochasticity around that time. We then project this uncertainty forwards in time using an ordinary differential equation model in order to obtain a distribution for the peak timing of the epidemic that agrees closely with large simulations but that, for error tolerances relevant to most realistic applications, requires a fraction of the computational cost of full Monte Carlo approaches.

During an infectious disease outbreak, biases in the data and complexities of the underlying dynamics pose significant challenges in mathematically modelling the outbreak and designing policy. Motivated by the ongoing response to COVID-19, we provide a toolkit of statistical and mathematical models beyond the simple SIR-type differential equation models for analysing the early stages of an outbreak and assessing interventions. In particular, we focus on parameter estimation in the presence of known biases in the data, and the effect of non-pharmaceutical interventions in enclosed subpopulations, such as households and care homes. We illustrate these methods by applying them to the COVID-19 pandemic.

Early assessments of the spreading rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but more reliable inferences can now be made. Here, we estimate from European data that COVID-19 cases are expected to double initially every three days, until social distancing interventions slow this growth, and that the impact of such measures is typically only seen nine days - i.e. three doubling times - after their implementation. We argue that such temporal patterns are more critical than precise estimates of the basic reproduction number for initiating interventions. This observation has particular implications for the low- and middle-income countries currently in the early stages of their local epidemics., Comment: Main text: 13 pages (1-13), 3 figures, 1 table; Supplementary Information: 9 pages (14-22), 4 figures, 1 table