Renewal processes are a popular approach used in modelling infectious disease outbreaks. In a renewal process, previous infections give rise to future infections. However, while this formulation seems sensible, its application to infectious disease can be difficult to justify from first principles. It has been shown from the seminal work of Bellman and Harris that the renewal equation arises as the expectation of an age-dependent branching process. In this paper we provide a detailed derivation of the original Bellman Harris process. We introduce generalisations, that allow for time-varying reproduction numbers and the accounting of exogenous events, such as importations. We show how inference on the renewal equation is easy to accomplish within a Bayesian hierarchical framework. Using off the shelf MCMC packages, we fit to South Korea COVID-19 case data to estimate reproduction numbers and importations. Our derivation provides the mathematical fundamentals and assumptions underpinning the use of the renewal equation for modelling outbreaks.
We propose a general Bayesian approach to modeling epidemics such as COVID-19. The approach grew out of specific analyses conducted during the pandemic, in particular an analysis concerning the effects of non-pharmaceutical interventions (NPIs) in reducing COVID-19 transmission in 11 European countries. The model parameterizes the time varying reproduction number $R_t$ through a regression framework in which covariates can e.g be governmental interventions or changes in mobility patterns. This allows a joint fit across regions and partial pooling to share strength. This innovation was critical…
We investigate the global dynamics of a renewal-type epidemic model with variable susceptibility. We show that in this extended model there exists a unique endemic equilibrium and prove that it is globally asymptotically stable when $R_0 > 1$, i.e. when it exists. We also show that the infection-free equilibrium, which exists always, is globally asymptotically stable for $R_0 \leq 1$.
The expected number of secondary infections arising from each index case, referred to as the reproduction or $R$ number, is a vital summary statistic for understanding and managing epidemic diseases. There are many methods for estimating $R$; however, few explicitly model heterogeneous disease reproduction, which gives rise to superspreading within the population. We propose a parsimonious discrete-time branching process model for epidemic curves that incorporates heterogeneous individual reproduction numbers. Our Bayesian approach to inference illustrates that this heterogeneity results in le…
We use analytical methods to investigate a continuous vaccination strategy effects on the infectious disease dynamics in a closed population and a demographically open population. The methodology and key assumptions are based on Breda et al (2012). We show that the cumulative force of infection for the closed population and the endemic force of infection in the demographically open population can be reduced significantly by combining two factors: the vaccine effectiveness and the vaccination rate. The impact of these factors on the force of infection can transform an endemic steady state into …
Assessing the performance of compartmental and renewal models for learning $R_{t}$ using spatially heterogeneous epidemic simulations on real geographies
Renewal equations are a popular approach used in modelling the number of new infections, i.e., incidence, in an outbreak. We develop a stochastic model of an outbreak based on a time-varying variant of the Crump-Mode-Jagers branching process. This model accommodates a time-varying reproduction number and a time-varying distribution for the generation interval. We then derive renewal-like integral equations for incidence, cumulative incidence and prevalence under this model. We show that the equations for incidence and prevalence are consistent with the so-called back-calculation relationship. …
This article introduces epidemia, an R package for Bayesian, regression-oriented modeling of infectious diseases. The implemented models define a likelihood for all observed data while also explicitly modeling transmission dynamics: an approach often termed as semi-mechanistic. Infections are propagated over time using renewal equations. This approach is inspired by self-exciting, continuous-time point processes such as the Hawkes process. A variety of inferential tasks can be performed using the package. Key epidemiological quantities, including reproduction numbers and latent infections, may…
Explicit mathematical epidemiology results on age renewal kernels and R0 formulas are often consequences of the rank one property of the next generation matrix
Stochastic monotonicity and continuity properties of functions defined on Crump-Mode-Jagers branching processes, with application to vaccination in epidemic modelling
A significant proportion of the infections driving the current {SARS-CoV-2} pandemic are transmitted asymptomatically. Here we introduce and study a simple epidemic model with separate compartments comprising asymptomatic and symptomatic infected individuals. The linear dynamics determining the outbreak condition of the model is equivalent to a renewal theory approach with exponential waiting time distributions. Exploiting a nontrivial conservation law of the full nonlinear dynamics, we derive analytic bounds on the peak number of infections in the absence and presence of mitigation through is…
We introduce a theoretical framework that highlights the impact of physical distancing variables such as human mobility and physical proximity on the evolution of epidemics and, crucially, on the reproduction number. In particular, in response to the coronavirus disease (CoViD-19) pandemic, countries have introduced various levels of 'lockdown' to reduce the number of new infections. Specifically we use a collisional approach to an infection-age structured model described by a renewal equation for the time homogeneous evolution of epidemics. As a result, we show how various contributions of th…
During the COVID pandemic, periods of exponential growth of the disease have been mitigated by containment measures that in different occasions have resulted in a power-law growth of the number of cases. The first observation of such behaviour has been obtained from 2020 late spring data coming from China by Ziff and Ziff in Ref. [1]. After this important observation the power-law scaling (albeit with different exponents) has also been observed in other countries during periods of containment of the spread. Early interpretations of these results suggest that this phenomenon might be due to spa…
Consider a Markovian SIR epidemic model in a homogeneous community. To this model we add a rate at which individuals are tested, and once an infectious individual tests positive it is isolated and each of their contacts are traced and tested independently with some fixed probability. If such a traced individual tests positive it is isolated, and the contact tracing is iterated. This model is analysed using large population approximations, both for the early stage of the epidemic when the "to-be-traced components" of the epidemic behaves like a branching process, and for the main stage of the e…
Epidemic spreading can be suppressed by the introduction of containment measures such as social distancing and lock downs. Yet, when such measures are relaxed, new epidemic waves and infection cycles may occur. Here we explore this issue in compartmentalized epidemic models on graphs in presence of a feedback between the infection state of the population and the structure of its social network for the case of discontinuous control. We show that in random graphs the effect of containment measures is simply captured by a renormalization of the effective infection rate that accounts for the chang…
The interplay of biological, social, structural and random factors makes disease forecasting extraordinarily complex. The course of an epidemic exhibits average growth dynamics determined by features of the pathogen and the population, yet also features significant variability reflecting the stochastic nature of disease spread. In this work, we reframe a stochastic branching process analysis in terms of probability generating functions and compare it to continuous time epidemic simulations on networks. In doing so, we predict the diversity of emerging epidemic courses on both homogeneous and h…
Our paper presents three new classes of models: SIR-PH, SIR-PH-FA, and SIR-PH-IA, and states two problems we would like to solve about them. Recall that deterministic mathematical epidemiology has one basic general law, the R0 alternative" of [52, 51], which states that the local stability condition of the disease free equilibrium may be expressed as R0 < 1, where R0 is the famous basic reproduction number, which plays also a major role in the theory of branching processes. The literature suggests that it is impossible to find general laws concerning the endemic points. However, it is quite co…
A population can be immune to epidemics even if not all of its individual members are immune to the disease, so long as sufficiently many are immune - this is the traditional notion of herd immunity. In the smartphone era a population can be immune to epidemics even if not a single one of its members is immune to the disease - a notion we call "digital herd immunity", which is similarly an emergent characteristic of the population. This immunity arises because contact-tracing protocols based on smartphone capabilities can lead to highly efficient quarantining of infected population members and…
Branching processes are widely used to model evolutionary and population dynamics as well as the spread of infectious diseases. To characterize the dynamics of their growth or spread, the basic reproduction number $R_0$ has received considerable attention. In the context of infectious diseases, it is usually defined as the expected number of secondary cases produced by an infectious case in a completely susceptible population. Typically $R_0>1$ indicates that an outbreak is expected to continue and to grow exponentially, while $R_0<1$ usually indicates that an outbreak is expected to terminate…
Reproduction Numbers R_0, R_t for COVID-19 Infections with Gaussian Distribution of Generation Times, and of Serial Intervals including Presymptomatic Transmission
Multitype branching processes are ideal for studying the population dynamics of stem cell populations undergoing mutation accumulation over the years following transplant. In such stochastic models, several quantities are of clinical interest as insertional mutagenesis carries the potential threat of leukemogenesis following gene therapy with autologous stem cell transplantation. In this paper, we develop a three-type branching process model describing accumulations of mutations in a population of stem cells distinguished by their ability for long-term self-renewal. Our outcome of interest is …
As of October 12, 2018, 211 cases of Ebola virus disease (EVD) were reported in North Kivu Province, Democratic Republic of Congo. Since the beginning of October the outbreak has largely shifted into regions in which active armed conflict is occurring, and in which EVD cases and their contacts are difficult for health workers to reach. We modeled EVD transmission using a branching process with gradually quenching transmission estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination co…
