The basic reproductive number -- $R_0$ -- is one of the most common and most commonly misapplied numbers in public health. Although often used to compare outbreaks and forecast pandemic risk, this single number belies the complexity that two different pathogens can exhibit, even when they have the same $R_0$. Here, we show how to predict outbreak size using estimates of the distribution of secondary infections, leveraging both its average $R_0$ and the underlying heterogeneity. To do so, we reformulate and extend a classic result from random network theory that relies on contact tracing data to simultaneously determine the first moment ($R_0$) and the higher moments (representing the heterogeneity) in the distribution of secondary infections. Further, we show the different ways in which this framework can be implemented in the data-scarce reality of emerging pathogens. Lastly, we demonstrate that without data on the heterogeneity in secondary infections for emerging infectious diseases like COVID-19, the uncertainty in outbreak size ranges dramatically. Taken together, our work highlights the critical need for contact tracing during emerging infectious disease outbreaks and the need to look beyond $R_0$ when predicting epidemic size.
We study a susceptible-vaccinated--infected--recovered (SVIR) epidemic-spreading model with diversity of infection rate of the individuals. By means of analytical arguments as well as extensive computer simulations, we demonstrate that the heterogeneity in infection rate can either impede or accelerate the epidemic spreading, which depends on the amount of vaccinated individuals introduced in the population as well as the contact pattern among the individuals. Remarkably, as long as the individuals with different capability of acquiring the disease interact with unequal frequency, there always…
The epidemic threshold of a spreading process indicates the condition for the occurrence of the wide spreading regime, thus representing a predictor of the network vulnerability to the epidemic. Such threshold depends on the natural history of the disease and on the pattern of contacts of the network with its time variation. Based on the theoretical framework introduced in (Valdano et al. PRX 2015) for a susceptible-infectious-susceptible model, we formulate here an infection propagator approach to compute the epidemic threshold accounting for more realistic effects regarding a varying force o…
We discuss various models for epidemics on networks that rely on Markov chains. Random walks on graphs are often used to predict epidemic spread and to investigate possible control actions to mitigate them. In this study, we demonstrate that they do not fully reflect the dynamics of epidemics, as they overestimate infection times. Accordingly, we explain how Markov chains may still be used to accurately model the virus spread, and to correctly predict infection times. We also provide an algorithm that efficiently estimates infection times via a sampling strategy. Finally, we present a novel in…
We analyse the infection-age-dependent SIR model from a numerical point of view. First, we present an algorithm for calculating the solution the infection-age-structured SIR model without demography of the background host. Second, we examine how and under which conditions, the conventional SIR model (without infection-age) serves as a practical approximation to the infection-age SIR model. Special emphasis is given on the effective reproduction number.
We propose an SEIR model for the populations and an SEI model for the vector to describe the transmission dynamics of a four-strain model with both primary and secondary dengue infections. In order to accomplish this, we propose and obtain an analytic solution of a system of 47 coupled differential equations. This would be the most complete epidemic model proposed to describe the dengue epidemic.
Nowcasting and forecasting of epidemic spreading rely on incidence series of reported cases to derive the fundamental epidemiological parameters for a given pathogen. Two relevant drawbacks for predictions are the unknown fractions of undocumented cases and levels of nonpharmacological interventions, which span highly heterogeneously across different places and times. We describe a simple data-driven approach using a compartmental model including asymptomatic and presymptomatic contagions that allows to estimate both the level of undocumented infections and the value of effective reproductive …
The epidemic spreading has been widely studied when each node may get infected by an infected neighbor with the same rate. However, the infection rate between a pair of nodes is usually heterogeneous and even correlated with their nodal degrees in the contact network. We aim to understand how such correlated heterogeneous infection rates influence the spreading on different network topologies. Motivated by real-world datasets, we propose a correlated heterogeneous Susceptible-Infected-Susceptible model which assumes that the infection rate $β_{ij}(=β_{ji})$ between node $i$ and $j$ is correlat…
The epidemic spreading has been studied for years by applying the mean-field approach in both homogeneous case, where each node may get infected by an infected neighbor with the same rate, and heterogeneous case, where the infection rates between different pairs of nodes are different. Researchers have discussed whether the mean-field approaches could accurately describe the epidemic spreading for the homogeneous cases but not for the heterogeneous cases. In this paper, we explore under what conditions the mean-field approach could perform well when the infection rates are heterogeneous. In pa…
Emerging epidemics and local infection clusters are initially prone to stochastic effects that can substantially impact the epidemic trajectory. While numerous studies are devoted to the deterministic regime of an established epidemic, mathematical descriptions of the initial phase of epidemic growth are comparatively rarer. Here, we review existing mathematical results on the epidemic size over time, and derive new results to elucidate the early dynamics of an infection cluster started by a single infected individual. We show that the initial growth of epidemics that eventually take off is ac…
In this paper, we continue development of the new epidemiological model HIT, which is suitable for analyzing and predicting the propagation of COVID-19 epidemics. This is a discrete-time model allowing a reconstruction of the dynamics of asymptomatic virus holders using the available daily statistics on the number of new cases. We suggest to use a new indicator, the total infection rate, to distinguish the propagation and recession modes of the epidemic. We check our indicator on the available data for eleven different countries and for the whole world. Our reconstructions are very precise. In…
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…
A model of an Ebola epidemic is developed with infected individuals structured according to disease age. The transmission of the infection is tracked by disease age through an initial incubation (exposed) phase, followed by an infectious phase with variable transmission infectiousness. The removal of infected individuals is dependent on disease age, with three types of removal rates: (1) removal due to hospitalization (isolation), (2) removal due to mortality separate from hospitalization, and (3) removal due to recovery separate from hospitalization. The model is applied to the Ebola epidemic…
We propose an SEIR-type meta-population model to simulate and monitor the Covid-19 epidemic evolution. The basic model consists of seven compartments, namely susceptible (S), exposed (E), three infective classes, recovered (R), and deceased (D). We define these compartments for n age and gender groups in m different spatial locations. So, the resulting model has, for each age group, gender, and place, all epidemiological classes. The mixing between them is accomplished by means of time-dependent infection rate matrices. The model is calibrated with the curve of daily new infections in New York…
In this work we study a modified Susceptible-Infected-Susceptible (SIS) model in which the infection rate $λ$ decays exponentially with the number of reinfections $n$, saturating after $n=l$. We find a critical decaying rate $ε_{c}(l)$ above which a finite fraction of the population becomes permanently infected. From the mean-field solution and computer simulations on hypercubic lattices we find evidences that the upper critical dimension is 6 like in the SIR model, which can be mapped in ordinary percolation.
We study a mosquito-borne epidemic model where the vector population is distinct in aquatic and adult stages and a saturating effect of disease transmission is assumed to ocurr when the number of infectious (humans and mosquitoes) becomes large enough. Several techniques, including center manifold analysis and sensitivity analysis, have been used to reveal relevant features of the model dynamics. We determine the existence of stability-instability thresholds and the individual role played in such thresholds by the model parameters.
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 spread of certain diseases can be promoted, in some cases substantially, by prior infection with another disease. One example is that of HIV, whose immunosuppressant effects significantly increase the chances of infection with other pathogens. Such coinfection processes, when combined with nontrivial structure in the contact networks over which diseases spread, can lead to complex patterns of epidemiological behavior. Here we consider a mathematical model of two diseases spreading through a single population, where infection with one disease is dependent on prior infection with the other. …
We define and examine a model of epidemic propagation for a virus such as Hepatitis C (with HIV co-infection) on a network of networks, namely the network of French urban areas. One network level is that of the individual interactions inside each urban area. The second level is that of the areas themselves, linked by individuals travelling between these areas and potentially helping the epidemic spread from one city to another. We choose to encode the second level of the network as extra, special nodes in the first level. We observe that such an encoding leads to sensible results in terms of t…
We develop a theory for the susceptible-infected-susceptible (SIS) epidemic model on networks that incorporate both network structure and dynamic correlations. This theory can account for the multistage onset of the epidemic phase in scale-free networks. This phenomenon is characterized by multiple peaks in the susceptibility as a function of the infection rate. It can be explained by that, even under the global epidemic threshold, a hub can sustain the epidemics for an extended period. Moreover, our approach improves theoretical calculations of prevalence close to the threshold in heterogeneo…
Contacts between individuals serve as pathways where infections may propagate. These contact patterns can be represented by network structures. Static structures have been the common modeling paradigm but recent results suggest that temporal structures play different roles to regulate the spread of infections or infection-like dynamics. On temporal networks a vertex is active only at certain moments and inactive otherwise such that a contact is not continuously available. In several empirical networks, the time between two consecutive vertex-activation events typically follows heterogeneous ac…
Transmission rates in epidemic outbreaks may vary over time depending on the societal response. Non-pharmacological mitigation strategies such as social distancing and the adoption of protective equipment aim precisely at reducing transmission rates by reducing infectious contacts. To investigate the effects of mitigation strategies on the evolution of epidemics, nonlinear transmission rates that are influenced by the levels of infections, deaths or recoveries have been included in many variants of the classical SIR model. This class of models is particularly relevant to the COVID-19 epidemic,…
This paper is concerned with SIR (susceptible $\to$ infected $\to$ removed) household epidemic models in which the infection response may be either mild or severe, with the type of response also affecting the infectiousness of an individual. Two different models are analysed. In the first model, the infection status of an individual is predetermined, perhaps due to partial immunity, and in the second, the infection status of an individual depends on the infection status of its infector and on whether the individual was infected by a within- or between-household contact. The first scenario may …
Traveling waves are analyzed in a model of the Hantavirus infection of deer mice. The existence of two kinds of wave phenomena is predicted. An environmental parameter governs a transition between two regimes of propagation. In one of them the front of infection lags behind at a constant rate. In the other, fronts of susceptible and infected mice travel at the same speed, separated by a constant delay. The dependence of the delay on system parameters is analyzed numerically and through a piecewise linearization.
A model of reactive social distancing in epidemics is proposed, in which the infection rate changes with the number infected. The final-size equation for the total number that the epidemic will infect can be derived analytically, as can the peak infection proportion. This model could assist planners during for example the COVID-19 pandemic.
A simple, but ``classical``, stochastic model for epidemic spread in a finite, but large, population is studied. The progress of the epidemic can be divided into three different phases that requires different tools to analyse. Initially the process is approximated by a branching process. It is discussed for how long time this approximation is valid. When a non-negligible proportion of the population is already infected the process can be studied using differential equations. In a final phase the spread will fade out. The results are used to investigate what happens if two strains of infectious…
We study the phase transition from the persistence phase to the extinction phase for the SIRS (susceptible/ infected/ refractory/ susceptible) model of diseases spreading on the networks. We derive an analytical expression of the probability for the descendants nodes to re-infect their ancestors nodes. We find that, in the case of the recovery time $τ_R$ is larger than the infection time $τ_I$, the infection will flow directionally from the ancestors to the descendants however, the descendants will not able to reinfect their ancestors during their infection time. This behavior leads us to dedu…
In this paper, we show how to modify a compartmental epidemic model, without changing the dimension, such that separable static heterogeneity is taken into account. The derivation is based on the Kermack-McKendrick renewal equation.
While COVID-19 is rapidly propagating around the globe, the need for providing real-time forecasts of the epidemics pushes fits of dynamical and statistical models to available data beyond their capabilities. Here we focus on statistical predictions of COVID-19 infections performed by fitting asymptotic distributions to actual data. By taking as a case-study the epidemic evolution of total COVID-19 infections in Chinese provinces and Italian regions, we find that predictions are characterized by large uncertainties at the early stages of the epidemic growth. Those uncertainties significantly r…
An actively controlled Susceptible-Infected-Susceptible (actSIS) contagion model is presented for studying epidemic dynamics with continuous-time feedback control of infection rates. Our work is inspired by the observation that epidemics can be controlled through decentralized disease-control strategies such as quarantining, sheltering in place, social distancing, etc., where individuals actively modify their contact rates with others in response to observations of infection levels in the population. Accounting for a time lag in observations and categorizing individuals into distinct sub-popul…
The dynamics of contact networks and epidemics of infectious diseases often occur on comparable time scales. Ignoring one of these time scales may provide an incomplete understanding of the population dynamics of the infection process. We develop an individual-based approximation for the susceptible-infected-recovered epidemic model applicable to arbitrary dynamic networks. Our framework provides, at the individual-level, the probability flow over time associated with the infection dynamics. This computationally efficient framework discards the correlation between the states of different nodes…
In this paper, we have studied epidemiological models for Ebola infection using nonlinear ordinary differential equations and optimal control theory. We considered optimal control analysis of SIR and SEIR models for the deadly Ebola infection using vaccination, treatment and educational campaign as time-dependent controls functions. We have applied indirect methods to study existing deterministic optimal control epidemic models for Ebola virus disease. These methods in optimal control are based on Hamiltonian function and the Pontryagin's maximum principle to construct adjoint equations and op…
This paper investigates the effect of the structure of the contact network on the dynamics of the epidemic outbreak. In particular, we focus on the peak number of critically infected nodes (PCIN), determining the maximum workload of intensive healthcare units which should be kept low. As a model and simulation method, we develop a continuous-time Markov chain (CTMC) model and an efficient simulation-based on Gillespie's Stochastic Simulation Algorithm (SSA). This methods combine a realistic approximation of the stochastic process not relying on the assumptions of mean-field models and large as…
The COVID-19 epidemic has been spreading around the world for nearly three years, and asymptomatic infections have exacerbated the spread of the epidemic. To evaluate the role of asymptomatic infections in the spread of the epidemic, we develop mathematical models to assess the proportion of asymptomatic infections caused by different strains of the main covid-19 variants. The analysis shows that when the control reproduction number is less than 1, the disease-free equilibrium point of the model is globally asymptotically stable; and when the control reproduction number is greater than 1, the …
This paper investigates the dynamics of infectious diseases with a non-exponentially distributed infectious period. This is achieved by considering a multi-stage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to t…
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 …
Population heterogeneity, especially in individuals' contact networks, plays an important role in transmission dynamics of infectious diseases. For vaccine-preventable diseases, outstanding issues like vaccine hesitancy and availability of vaccines further lead to nonuniform coverage among groups, not to mention the efficacy of vaccines and the mixing pattern varying from one group to another. As the ongoing COVID-19 pandemic transitions to endemicity, it is of interest and significance to understand the impact of aforementioned population heterogeneity on the emergence and persistence of epid…
In contrast to the common assumption in epidemic models that the rate of infection between individuals is constant, in reality, an individual's viral load determines their infectiousness. We compare the average and individual reproductive numbers and epidemic dynamics for a model incorporating time-dependent infectiousness and a standard SIR model for both fully-mixed and category-mixed populations. We find that the reproductive number only depends on the total infectious exposure and the largest eigenvalue of the mixing matrix and that these two effects are independent of each other. When we …
Efficient allocation of limited medical resources is crucial for controlling epidemic spreading on networks. Based on the susceptible-infected-susceptible model, we solve an optimization problem as how best to allocate the limited resources so as to minimize the prevalence, providing that the curing rate of each node is positively correlated to its medical resource. By quenched mean-field theory and heterogeneous mean-field (HMF) theory, we prove that epidemic outbreak will be suppressed to the greatest extent if the curing rate of each node is directly proportional to its degree, under which …
We review and introduce a generalized reaction-diffusion approach to epidemic spreading in a metapopulation modeled as a complex network. The metapopulation consists of susceptible and infected individuals that are grouped in subpopulations symbolising cities and villages that are coupled by human travel in a transportation network. By analytic methods and numerical simulations we calculate the fraction of infected people in the metaopoluation in the long time limit, as well as the relevant parameters characterising the epidemic threshold that separates an epidemic from a non-epidemic phase. W…
We generalize the Susceptible-Infected-Removed model for epidemics to take into account generic effects of heterogeneity in the degree of susceptibility to infection in the population. We introduce a single new parameter corresponding to a power-law exponent of the susceptibility distribution that characterizes the population heterogeneity. We show that our generalized model is as simple as the original model which is contained as a limiting case. Because of this simplicity, numerical solutions can be generated easily and key properties of the epidemic wave can still be obtained exactly. In pa…
We formulate a general age-of-infection epidemic model with two pathways: the symptomatic infections and the asymptomatic infections. We then calculate the basic reproduction number $\mathcal{R}_0$ and establish the final size relation. It is shown that the ratio of accumulated counts of symptomatic patients and asymptomatic patients is determined by the symptomatic ratio $f$ which is defined as the probability of eventually becoming symptomatic after being infected. We also formulate and study a general age-of-infection model with disease deaths and with two infection pathways. The final size…
Clinical trials of a vaccine during an epidemic face particular challenges, such as the pressure to identify an effective vaccine quickly to control the epidemic, and the effect that time-space-varying infection incidence has on the power of a trial. We illustrate how the operating characteristics of different trial design elements may be evaluated using a network epidemic and trial simulation model, based on COVID-19 and individually randomised two-arm trials with a binary outcome. We show that "ring" recruitment strategies, prioritising participants at high risk of infection, can result in s…
We present a model for the growth of West Nile virus in mosquito and bird populations based on observations of the initial epidemic in the U.S. Increase of bird mortality as a result of infection, which is a feature of the epidemic, is found to yield an effect which is observable in principle, viz., periodic variations in the extent of infection. The vast difference between mosquito and bird lifespans, another peculiarity of the system, is shown to lead to interesting consequences regarding delay in the onset of the steady-state infection. An outline of a framework is provided to treat mosquit…
We investigate the global dynamics of a general Kermack-McKendrick-type epidemic model formulated in terms of a system of renewal equations. Specifically, we consider a renewal model for which both the force of infection and the infected removal rates are arbitrary functions of the infection age, $τ$, and use the direct Lyapunov method to establish the global asymptotic stability of the equilibrium solutions. In particular, we show that the basic reproduction number, $R_0$, represents a sharp threshold parameter such that for $R_0\leq 1$, the infection-free equilibrium is globally asymptotical…
In the Susceptible-Infectious-Recovered (SIR) model of disease spreading, the time to extinction of the epidemics happens at an intermediate value of the per-contact transmission probability. Too contagious infections burn out fast in the population. Infections that are not contagious enough die out before they spread to a large fraction of people. We characterize how the maximal extinction time in SIR simulations on networks depend on the network structure. For example we find that the average distances in isolated components, weighted by the component size, is a good predictor of the maximal…
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…
Surveillance data serving for epidemic alert systems are typically fully aggregated in space. However, epidemics may be spatially heterogeneous, undergoing distinct dynamics in distinct regions of the surveillance area. We unveil this in retrospective analyses by classifying incidence time series. We use Pearson correlation to quantify the similarity between local time series and then classify them using modularity maximization. The surveillance area is thus divided into regions with different incidence patterns. We analyzed 31 years of data on influenza-like-illness from the French system Sen…
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…
In this paper we investigate a susceptible-infected-susceptible (SIS) epidemic model describing data dissemination in opportunistic networks with heterogeneous setting of transmission parameters. We obtained the estimation of the final epidemic size assuming that amount of data transferred between network nodes possesses a Pareto distribution, implying scale-free properties. In this context, more heterogeneity in susceptibility means the less severe epidemic progression, and, on the contrary, more heterogeneity in infectivity leads to more severe epidemics -- assuming that the other parameter …
A new method is proposed to infer unobserved epidemic sub-populations by exploiting the synchronization properties of multistrain epidemic models. A model for dengue fever is driven by simulated data from secondary infective populations. Primary infective populations in the driven system synchronize to the correct values from the driver system. Most hospital cases of dengue are secondary infections, so this method provides a way to deduce unobserved primary infection levels. We derive center manifold equations that relate the driven system to the driver system and thus motivate the use of sync…
