We study the spread of susceptible-infected-recovered (SIR) infectious diseases where an individual's infectiousness and probability of recovery depend on his/her "age" of infection. We focus first on early outbreak stages when stochastic effects dominate and show that epidemics tend to happen faster than deterministic calculations predict. If an outbreak is sufficiently large, stochastic effects are negligible and we modify the standard ordinary differential equation (ODE) model to accommodate age-of-infection effects. We avoid the use of partial differential equations which typically appear in related models. We introduce a "memoryless" ODE system which approximates the true solutions. Finally, we analyze the transition from the stochastic to the deterministic phase.
For practical reasons, many forecasts of case, hospitalization and death counts in the context of the current COVID-19 pandemic are issued in the form of central predictive intervals at various levels. This is also the case for the forecasts collected in the COVID-19 Forecast Hub (https://covid19forecasthub.org/). Forecast evaluation metrics like the logarithmic score, which has been applied in several infectious disease forecasting challenges, are then not available as they require full predictive distributions. This article provides an overview of how established methods for the evaluation o…
Many disease models focus on characterizing the underlying transmission mechanism but make simple, possibly naive assumptions about how infections are reported. In this note, we use a simple deterministic Susceptible-Infected-Removed (SIR) model to compare two common assumptions about disease incidence reports: individuals can report their infection as soon as they become infected or as soon as they recover. We show that incorrect assumptions about the underlying observation processes can bias estimates of the basic reproduction number and lead to overly narrow confidence intervals.
In epidemiological modelings, the spectral radius of the next generation matrix evaluated at the trivial equilibrium was considered as the basic reproduction number. Also, the global stability of the trivial equilibrium point was determined by the left eigenvector associated to that next generation matrix. More recently, the fraction of susceptible individuals was also obtained from the next generation matrix. By revisiting drug sensitive and resistant tuberculosis model, the gross reproduction number and the fraction of susceptible individuals are calculated. Hence, the next generation matric…
Dynamic models - often deterministic in nature - were used to estimate the basic reproductive number, R_0, of the 2014-5 Ebola virus disease (EVD) epidemic outbreak in West Africa. Estimates of R_0 were then used to project the likelihood for large outbreak sizes, e.g., exceeding hundreds of thousands of cases. Yet fitting deterministic models can lead to over-confidence in the confidence intervals of the fitted R_0, and, in turn, the type and scope of necessary interventions. In this manuscript we propose a hybrid stochastic-deterministic method to estimate R_0 and associated confidence inter…
The goal of this work is to analyse the effects of control policies for the coronavirus (COVID-19) epidemic in Brazil. This is done by considering an age-structured SEIR model with a quarantine class and two types of controls. The first one studies the sensitivity with regard to the parameters of the basic reproductive number R0 which is calculated by the next generation method. The second one evaluates different quarantine strategies by comparing their relative total number of deaths.
We propose a stochastic SIR model, specified as a system of stochastic differential equations, to analyse the data of the Italian COVID-19 epidemic, taking also into account the under-detection of infected and recovered individuals in the population. We find that a correct assessment of the amount of under-detection is important to obtain reliable estimates of the critical model parameters. Moreover, a single SIR model over the whole epidemic period is unable to correctly describe the behaviour of the pandemic. Then, the adaptation of the model in every time-interval between relevant governmen…
Background: While many infectious disease epidemics are initially characterized by an exponential growth in time, we show that district-level Ebola virus disease (EVD) outbreaks in West Africa follow slower polynomial-based growth kinetics over several generations of the disease. Methods: We analyzed epidemic growth patterns at three different spatial scales (regional, national, and subnational) of the Ebola virus disease epidemic in Guinea, Sierra Leone and Liberia by compiling publicly available weekly time series of reported EVD case numbers from the patient database available from the Worl…
In most models of the spread of disease over contact networks it is assumed that the probabilities per unit time of disease transmission and recovery from disease are constant, implying exponential distributions of the time intervals for transmission and recovery. Time intervals for real diseases, however, have distributions that in most cases are far from exponential, which leads to disagreements, both qualitative and quantitative, with the models. In this paper, we study a generalized version of the SIR (susceptible-infected-recovered) model of epidemic disease that allows for arbitrary dist…
We present a stochastic epidemic model to study the effect of various preventive measures, such as uniform reduction of contacts and transmission, vaccination, isolation, screening and contact tracing, on a disease outbreak in a homogeneously mixing community. The model is based on an infectivity process, which we define through stochastic contact and infectiousness processes, so that each individual has an independent infectivity profile. In particular, we monitor variations of the reproduction number and of the distribution of generation times. We show that some interventions, i.e. uniform r…
Early estimates of the transmission potential of emerging and re-emerging infections are increasingly used to inform public health authorities on the level of risk posed by outbreaks. Existing methods to estimate the reproduction number generally assume exponential growth in case incidence in the first few disease generations, before susceptible depletion sets in. In reality, outbreaks can display sub-exponential (i.e., polynomial) growth in the first few disease generations, owing to clustering in contact patterns, spatial effects, inhomogeneous mixing, reactive behavior changes, or other mec…
It is common to use a compartmental, fluid model described by a system of ordinary differential equations (ODEs) to model disease spread. In addition to their simplicity, these models are also the mean-field approximations of more accurate stochastic models of disease spread on contact networks. For the simplest case of a stochastic susceptible-infected-susceptible (SIS) process (infection with recovery) on a complete network, it has been shown that the fraction of infected nodes converges to the mean-field ODE as the number of nodes increases. However the proofs are not simple, requiring soph…
We introduce a modified SIR model with memory for the dynamics of epidemic spreading in a constant population of individuals. Each individual is in one of the states susceptible (${\bf S}$), infected (${\bf I}$) or recovered (${\bf R}$). In the state ${\bf R}$ an individual is assumed to stay immune within a finite time interval. In the first part, we introduce a random life time or duration of immunity which is drawn from a certain probability density function. Once the time of immunity is elapsed an individual makes an instantaneous transition to the susceptible state. By introducing a rando…
Epidemic parameters are estimated through Bayesian inference using the daily fatality counts in Mumbai during the period from March 31 to April 14. A doubling time of 5.5 days (median with 95% CrI of 4.6-6.9 days) is observed. In the SEIR model this gives the basic reproduction rate R_0 of 3.4 (median with 95% CrI of 2.4-4.8). Using as input the infection fatality rate and the interval between infection and death, the number of infections in Mumbai is inferred. It is found that the ratio of the number of test positives to the total infections is 0.13\% (median), implying that tests are current…
Investigations of a possible connection between population density and the propagation and magnitude of epidemics have so far led to mixed and unconvincing results. There are three reasons for that. (i) Previous studies did not focus on the appropriate density interval. (ii) For the density to be a meaningful variable the population must be distributed as uniformly as possible. If an area has towns and cities where a majority of the population is concentrated its average density is meaningless. (iii) In the propagation of an epidemic the initial proportion of susceptibles (that is to say perso…
The recent COVID-19 pandemic has shown that when the reproduction number is high and there are no proper measurements in place, the number of infected people can increase dramatically in a short time, producing a phenomenon that many stochastic SIR-like models cannot describe: overdispersion of the number of infected people (i.e., the variance of the number of infected people during any interval is very high compared to the average). To address this issue, in this paper we explore the possibility of modeling the total number of infections as a state dependent self-exciting point process. In th…
Empirical studies suggest that contact patterns follow heterogeneous inter-event times, meaning that intervals of high activity are followed by periods of inactivity. Combined with birth and death of individuals, these temporal constraints affect the spread of infections in a non-trivial way and are dependent on the particular contact dynamics. We propose a stochastic model to generate temporal networks where vertices make instantaneous contacts following heterogeneous inter-event times, and leave and enter the system at fixed rates. We study how these temporal properties affect the prevalence…
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…
We propose an SEIARD mathematical model to investigate the current outbreak of coronavirus disease (COVID-19) in Mexico. We conduct a detailed analysis of this model and demonstrate its application using publicly reported data. We calculate the basic reproduction number ($R_0$) via the next-generation matrix method, and we estimate the per day infection, death and recovery rates. We calibrate the parameters of the SEIARD model to the reported data by minimizing the sum of squared errors and attempt to forecast the evolution of the outbreak until June 2020. Our results estimate that the peak of…
Reproduction Numbers R_0, R_t for COVID-19 Infections with Gaussian Distribution of Generation Times, and of Serial Intervals including Presymptomatic Transmission
Assessing the performance of compartmental and renewal models for learning $R_{t}$ using spatially heterogeneous epidemic simulations on real geographies
Explicit mathematical epidemiology results on age renewal kernels and R0 formulas are often consequences of the rank one property of the next generation matrix
The cascade model generates a food web at random. In it the species are labeled from 0 to $m$, and arcs are given at random between pairs of the species. For an arc with endpoints $i$ and $j$ ($i<j$), the species $i$ is eaten by the species labeled $j$. The chain length (height), generated at random, models the length of food chain in ecological data. The aim of this note is to introduce the random sequential generation of intervals as a Poisson model which gives naturally an analogous behavior to the cascade model.
Designing algorithms that generate networks with a given degree sequence while varying both subgraph composition and distribution of subgraphs around nodes is an important but challenging research problem. Current algorithms lack control of key network parameters, the ability to specify to what subgraphs a node belongs to, come at a considerable complexity cost or, critically, sample from a limited ensemble of networks. To enable controlled investigations of the impact and role of subgraphs, especially for epidemics, neuronal activity or complex contagion, it is essential that the generation p…
MEmilio -- A high performance Modular EpideMIcs simuLatIOn software for multi-scale and comparative simulations of infectious disease dynamics
German Aerospace Center（德国航空航天中心）；University of Bonn（波恩大学）；Helmholtz Centre for Infection Research（亥姆霍兹感染研究中心）；Forschungszentrum Jülich GmbH（于利希研究中心有限公司）
We present a series of SIR-network models, extended with a game-theoretic treatment of imitation dynamics which result from regular population mobility across residential and work areas and the ensuing interactions. Each considered SIR-network model captures a class of vaccination behaviours influenced by epidemic characteristics, interaction topology, and imitation dynamics. Our focus is the eventual vaccination coverage, produced under voluntary vaccination schemes, in response to these varying factors. Using the next generation matrix method, we analytically derive and compare expressions f…
Reproduction numbers, like the basic reproduction number $\mathcal{R}_0$, play an important role in the analysis and application of dynamic models, including contagion models and ecological population models. One difficulty in deriving these quantities is that they must be computed on a model-by-model basis, since it is typically impractical to obtain general reproduction number expressions applicable to a family of related models, especially if these are of different dimensions. For example, this is typically the case for SIR-type infectious disease models derived using the linear chain trick…
