Between pandemics, the influenza virus exhibits periods of incremental evolution via a process known as antigenic drift. This process gives rise to a sequence of strains of the pathogen that are continuously replaced by newer strains, preventing a build up of immunity in the host population. In this paper, a parsimonious epidemic model is defined that attempts to capture the dynamics of evolving strains within a host population. The `evolving strains' epidemic model has many properties that lie in-between the Susceptible-Infected-Susceptible and the Susceptible-Infected-Removed epidemic models, due to the fact that individuals can only be infected by each strain once, but remain susceptible to reinfection by newly emerged strains. Coupling results are used to identify key properties, such as the time to extinction. A range of reproduction numbers are explored to characterize the model, including a novel quasi-stationary reproduction number that can be used to describe the re-emergence of the pathogen into a population with `average' levels of strain immunity, analogous to the beginning of the winter peak in influenza. Finally the quasi-stationary distribution of the evolving strains model is explored via simulation.
Incidence of whooping cough, an infection caused by Bordetella pertussis and Bordetella parapertussis, has been on the rise since the 1980s in many countries. Immunological interactions, such as immune boosting and cross-immunity between pathogens, have been hypothesised to be important drivers of epidemiological dynamics. We present a two-pathogen model of transmission which examines how immune boosting and cross-immunity can influence the timing and severity of epidemics. We use a combination of numerical simulations and bifurcation techniques to study the dynamical properties of the system,…
SIRS epidemic models assume that individual immunity (from infection and vaccination) wanes in one big leap, from complete immunity to complete susceptibility. For many diseases immunity on the contrary wanes gradually, something that's become even more evident during COVID-19 pandemic where also recently infected have a reinfection risk, and where booster vaccines are given to increase immunity. This paper considers an epidemic model allowing for such gradual waning of immunity (either linear or exponential waning) thereby extending SIRS epidemics, and also incorporates vaccination. The two v…
This paper examines the interplay of the effect of cross immunity and antibody-dependent enhancement (ADE) in mutistrain diseases. Motivated by dengue fever, we study a model for the spreading of epidemics in a population with multistrain interactions mediated by both partial temporary cross immunity and ADE. Although ADE models have previously been observed to cause chaotic outbreaks, we show analytically that weak cross immunity has a stabilizing effect on the system. That is, the onset of disease fluctuations requires a larger value of ADE with small cross immunity than without. However, st…
When the body gets infected by a pathogen or receives a vaccine dose, the immune system develops pathogen-specific immunity. Induced immunity decays in time and years after recovery/vaccination the host might become susceptible again. Exposure to the pathogen in the environment boosts the immune system thus prolonging the duration of the protection. Such an interplay of within host and population level dynamics poses significant challenges in rigorous mathematical modeling of immuno-epidemiology. The aim of this paper is twofold. First, we provide an overview of existing models for waning of d…
The immune system recognizes a myriad of invading pathogens and their toxic products. It does so with a finite repertoire of antibodies and T cell receptors. We here describe theories that quantify the immune system dynamics. We describe how the immune system recognizes antigens by searching the large space of receptor molecules. We consider in some detail the theories that quantify the immune response to influenza and dengue fever. We review theoretical descriptions of the complementary evolution of pathogens that occurs in response to immune system pressure. Methods including bioinformatics,…
This paper introduces a new multi-strain epidemic model with reinfection and cross-immunity to provide insights into the resurgence of the COVID-19 epidemic in an area with reportedly high seroprevalence due to a largely unmitigated outbreak: the state of Amazonas, Brazil. Although high seroprevalence could have been expected to trigger herd immunity and prevent further waves in the state, we have observed persistent levels of infection after the first wave and eventually the emergence of a second viral strain just before an augmented second wave. Our experiments suggest that the persistent le…
Time varying susceptibility of host at individual level due to waning and boosting immunity is known to induce rich long-term behavior of disease transmission dynamics. Meanwhile, the impact of the time varying heterogeneity of host susceptibility on the shot-term behavior of epidemics is not well-studied, even though the large amount of the available epidemiological data are the short-term epidemics. Here we constructed a parsimonious mathematical model describing the short-term transmission dynamics taking into account natural-boosting immunity by reinfection, and obtained the explicit solut…
We analyse an extended SIRS epidemic model in which immunity at the individual level wanes gradually at exponential rate, but where the waning rate may differ between individuals, for instance as an effect of differences in immune systems. The model also includes vaccination schemes aimed to reach and maintain herd immunity. We consider both the informed situation where the individual waning parameters are known, thus allowing selection of vaccinees being based on both time since last vaccination as well as on the individual waning rate, and the more likely uninformed situation where individua…
We introduce and analyze coupled, multi-strain epidemic models designed to simulate the emergence and dissemination of mutant (e.g. drug-resistant) pathogen strains. In particular, we investigate the mathematical and biological properties of a general class of multi-strain epidemic models in which the infectious compartments of each strain are coupled together in a general manner. We derive explicit expressions for the basic reproduction number of each strain and highlight their importance in regulating the system dynamics (e.g. the potential for an epidemic outbreak) and the existence of nonn…
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…
The dynamics of epidemic spreading is often reduced to the single control parameter $R_0$, whose value, above or below unity, determines the state of the contagion. If, however, the pathogen evolves as it spreads, $R_0$ may change over time, potentially leading to a mutation-driven spread, in which an initially sub-pandemic pathogen undergoes a breakthrough mutation. To predict the boundaries of this pandemic phase, we introduce here a modeling framework to couple the network spreading patterns with the intra-host evolutionary dynamics. For many pathogens these two processes, intra- and inter-…
The global SARS-CoV-2 pandemic suggests a novel type of disease spread dynamics. WHO states that there is currently no evidence that people who have recovered from COVID-19 and have antibodies are immune from a second infection [WHO]. Conventional mathematical models consider cases for which a recovered individual either becomes susceptible again or develops an immunity. Here, we study the case where infected agents recover and only develop immunity if they are continuously infected for some time. Otherwise, they become susceptible again. We show that field theory bounds the peak of the infect…
We investigate the dynamics of a simple epidemiological model for the invasion by a pathogen strain of a population where another strain circulates. We assume that reinfection by the same strain is possible but occurs at a reduced rate due to acquired immunity. The rate of reinfection by a distinct strain is also reduced due to cross-immunity. Individual based simulations of this model on a `small-world' network show that the host contact network structure significantly affects the outcome of such an invasion, and as a consequence will affect the patterns of pathogen evolution. In particular, …
In this paper, we carry out a computational study using the spectral decomposition of the fluctuations of a two-pathogen epidemic model around its deterministic attractor, i.e., steady state or limit cycle, to examine the role of partial vaccination and between-host pathogen interaction on early pathogen replacement during seasonal epidemics of influenza and respiratory syncytial virus.
We performed a thorough sensitivity analysis of the herd immunity threshold for discrete-time SIR compartmental models with a static network structure. We find unexpectedly that these models violate classical intuition which holds that the herd immunity threshold should monotonically increase with the transmission parameter. We find the existence of bifurcations in the herd immunity threshold in the high transmission probability regime. The extent of these bifurcations is modulated by the graph heterogeneity, the recovery parameter, and the network size. In the limit of large, well-mixed netwo…
Pathogen introduction in plant communities can cause serious impact and biodiversity losses that may take long time to manage and restore. Effective control of epidemic spreading in the wild is a problem of paramount importance, because of its implications in conservation and potential economic losses. Understanding the mechanisms that hinder pathogen's propagation is, therefore, crucial. Usual modelization approaches in epidemic spreading are based in compartmentalized models, without keeping track of pathogen's concentrations during spreading. In this contribution we present and fully analyz…
Mathematical disease modelling has long operated under the assumption that any one infectious disease is caused by one transmissible pathogen spreading among a population. This paradigm has been useful in simplifying the biological reality of epidemics and has allowed the modelling community to focus on the complexity of other factors such as population structure and interventions. However, there is an increasing amount of evidence that the strain diversity of pathogens, and their interplay with the host immune system, can play a large role in shaping the dynamics of epidemics. Here, we introd…
COVID-19 will be a continuous threat to human population despite having a few vaccines at hand until we reach the endemic state through natural herd immunity and total immunization through universal vaccination. However, the vaccine acts as a practical tool for reducing the massive public health problem and the emerging economic consequences that the continuing COVID -19 epidemic is causing worldwide, while the vaccine efficacy wanes. In this work, we propose and analyze an epidemic model of Susceptible-Exposed-Infected-Recovered-Vaccinated (SEIRV) population taking into account the rate of va…
The Beyond-Linear-Use-of-Equation-Superposition (BLUES) function method is extended to coupled nonlinear ordinary differential equations and applied to the epidemiological SIRS model with vaccination. Accurate analytic approximations are obtained for the time evolution of the susceptible and infected population fractions. The results are compared with those obtained with alternative methods, notably Adomian decomposition, variational iteration and homotopy perturbation. In contrast with these methods, the BLUES iteration converges rapidly, globally, and captures the exact asymptotic behavior f…
Common respiratory viruses cause seasonal epidemics in sequential patterns. The underlying mechanisms for this pattern have been debated for some time. For influenza, contenders include temperature, humidity, and vitamin D levels. While such seasonal drivers may be sufficient to explain midwinter peaking it is unclear if other respiratory viruses peaking in spring, summer, or fall have individual environmental drivers. Here we present a dynamic model of interacting diseases, in an effort to explain observed seasonal patterns without requiring multiple seasonal drivers. Our model extends the cl…
Epidemics generally spread through a succession of waves that reflect factors on multiple timescales. On short timescales, super-spreading events lead to burstiness and overdispersion, while long-term persistent heterogeneity in susceptibility is expected to lead to a reduction in the infection peak and the herd immunity threshold (HIT). Here, we develop a general approach to encompass both timescales, including time variations in individual social activity, and demonstrate how to incorporate them phenomenologically into a wide class of epidemiological models through parameterization. We deriv…
Epidemiological contact network models have emerged as an important tool in understanding and predicting the spread of infectious disease, due to their capacity to engage individual heterogeneity that may underlie essential dynamics of a particular host-pathogen system. Just as fundamental are the changes that real-world contact networks undergo over time, both independently of and in response to pathogen spreading. These dynamics play a central role in determining whether a disease will die out or become an epidemic within a population, known as the epidemic threshold. In this paper, we provi…
Many pathogens spread primarily via direct contact between infected and susceptible hosts. Thus, the patterns of contacts or contact network of a population fundamentally shapes the course of epidemics. While there is a robust and growing theory for the dynamics of single epidemics in networks, we know little about the impacts of network structure on long term epidemic or endemic transmission. For seasonal diseases like influenza, pathogens repeatedly return to populations with complex and changing patterns of susceptibility and immunity acquired through prior infection. Here, we develop two m…
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…
Seasonal influenza kills hundreds of thousands every year, with multiple constantly-changing strains in circulation at any given time. A high mutation rate enables the influenza virus to evade recognition by the human immune system, including immunity acquired through past infection and vaccination. Here, we capture the genetic similarity of influenza strains and their evolutionary dynamics with genotype networks. We show that the genotype networks of influenza A (H3N2) hemagglutinin are characterized by heavy-tailed distributions of module sizes and connectivity, suggesting critical-like beha…
While a common trend in disease modeling is to develop models of increasing complexity, it was recently pointed out that outbreaks appear remarkably simple when viewed in the incidence vs. cumulative cases (ICC) plane. This article details the theory behind this phenomenon by analyzing the stochastic SIR (Susceptible, Infected, Recovered) model in the cumulative cases domain. We prove that the Markov chain associated with this model reduces, in the ICC plane, to a pure birth chain for the cumulative number of cases, whose limit leads to an independent increments Gaussian process that fluctuate…
Here we show that herd immunity is not a measure we can implement, trust, control or depend on, and that waiting for herd immunity to play a role is tantamount to hope for the best. Herd immunity is not some protection, as it has been referred to, but a reduction in the chance of infection that a population can achieve only if more infections occur, which is paradoxical. The discussion on when there will be enough herd immunity for the COVID-19 epidemics to halt, delivers the public and policy makers the wrong message that we can wait for something to happen to relax containment measures. Here…
Rapidly evolving pathogens like influenza viruses can persist by accumulating antigenic novelty fast enough to evade the adaptive immunity of the host population, yet without continuous accumulation of genetic diversity. This dynamical state is often compared to the Red Queen evolving as fast as it can just to maintain its foothold in the host population: Accumulation of antigenic novelty is balanced by the build-up of host immunity. Such Red Queen States (RQS) of continuous adaptation in large rapidly mutating populations are well understood in terms of Traveling Wave (TW) theories of populat…
Mechanisms of immunity, and of the host-pathogen interactions in general are among the most fundamental problems of medicine, ecology, and evolution studies. Here, we present a microscopic, protein-level, sequence-based model of immune system, with explicitly defined interactions between host and pathogen proteins.. Simulations of this model show that possible outcomes of the infection (extinction of cells, survival with complete elimination of viruses, or chronic infection with continuous coexistence of cells and viruses) crucially depend on mutation rates of the viral and immunoglobulin prot…
Ever since the outbreak of the COVID-19 epidemic, various public health control strategies have been proposed and tested against the coronavirus SARS-CoV-2. We study three specific COVID-19 epidemic control models: the susceptible, exposed, infectious, recovered (SEIR) model with vaccination control; the SEIR model with shield immunity control; and the susceptible, un-quarantined infected, quarantined infected, confirmed infected (SUQC) model with quarantine control. We express the control requirement in metric temporal logic (MTL) formulas (a type of formal specification languages) which can …
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…
Until a vaccine or therapy is found against the SARS-CoV-2 coronavirus, reaching herd immunity appears to be the only mid-term option. However, if the number of infected individuals decreases and eventually fades only beyond this threshold, a significant proportion of susceptible may still be infected until the epidemic is over. A containment strategy is likely the best policy in the worst case where no vaccine or therapy is found. In order to keep the number of newly infected persons to a minimum, a possible strategy is to apply strict containment measures, so that the number of susceptible i…
Modelling SARS-CoV-2 epidemics via compartmental and cellular automaton SEIRS model with temporal immunity and vaccination
Yukhnovskii Institute for Condensed Matter Physics of the National Academy of Sciences of Ukraine（乌克兰国家科学院尤赫诺夫斯基凝聚态物理研究所）；Institute of Applied Mathematics and Fundamental Sciences, Lviv Polytechnic National University（利沃夫国立理工大学应用数学与基础科学研究所）
Rapidly mutating pathogens may be able to persist in the population and reach an endemic equilibrium by escaping hosts' acquired immunity. For such diseases, multiple biological, environmental and population-level mechanisms determine the dynamics of the outbreak, including pathogen's epidemiological traits (e.g. transmissibility, infectious period and duration of immunity), seasonality, interaction with other circulating strains and hosts' mixing and spatial fragmentation. Here, we study a susceptible-infected-recovered-susceptible model on a metapopulation where individuals are distributed i…
Different pathogens spreading in the same host population often generate complex co-circulation dynamics because of the many possible interactions between the pathogens and the host immune system, the host life cycle, and the space structure of the population. Here we focus on the competition between two acute infections and we address the role of host mobility and cross-immunity in shaping possible dominance/co-dominance regimes. Host mobility is modelled as a network of traveling flows connecting nodes of a metapopulation, and the two-pathogen dynamics is simulated with a stochastic mechanis…
Quantifying the attack ratio of disease is key to epidemiological inference and Public Health planning. For multi-serotype pathogens, however, different levels of serotype-specific immunity make it difficult to assess the population at risk. In this paper we propose a Bayesian method for estimation of the attack ratio of an epidemic and the initial fraction of susceptibles using aggregated incidence data. We derive the probability distribution of the effective reproductive number, R t , and use MCMC to obtain posterior distributions of the parameters of a single-strain SIR transmission model w…
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…
Mathematical models of cholera and waterborne disease vary widely in their structures, in terms of transmission pathways, loss of immunity, and other features. These differences may yield different predictions and parameter estimates from the same data. Given the increasing use of models to inform public health decision-making, it is important to assess distinguishability (whether models can be distinguished based on fit to data) and inference robustness (whether model inferences are robust to realistic variations in model structure). We examined the effects of uncertainty in model structure i…
Traveling fronts in a spatial epidemic model with slow loss of immunity
University of Naples “Federico II”（那不勒斯费德里科二世大学）；Istituto Nazionale di Alta Matematica “F. Severi”（F·塞韦里高等数学国家研究所）；University of Palermo（巴勒莫大学）；Parthenope University of Naples（那不勒斯帕耳忒诺佩大学）；University of Trento（特伦托大学）
The contact structure of a population plays an important role in transmission of infection. Many ``structured models'' capture aspects of the contact structure through an underlying network or a mixing matrix. An important observation in such models, is that once a fraction $1-1/\mathcal{R}_0$ has been infected, the residual susceptible population can no longer sustain an epidemic. A recent observation of some structured models is that this threshold can be crossed with a smaller fraction of infected individuals, because the disease acts like a targeted vaccine, preferentially immunizing highe…
In this paper we conduct a simulation study of the spread of an epidemic like COVID-19 with temporary immunity on finite spatial and non-spatial network models. In particular, we assume that an epidemic spreads stochastically on a scale-free network and that each infected individual in the network gains a temporary immunity after its infectious period is over. After the temporary immunity period is over, the individual becomes susceptible to the virus again. When the underlying contact network is embedded in Euclidean geometry, we model three different intervention strategies that aim to contr…
Cooperation and competition between pathogens can alter the amount of individuals affected by a co-infection. Nonetheless, the evolution of the pathogens' behavior has been overlooked. Here, we consider a co-evolutionary model where the simultaneous spreading is described by a two-pathogen susceptible-infected-recovered model in an either synergistic or competitive manner. At the end of each epidemic season, the pathogens species reproduce according to their fitness that, in turn, depends on the payoff accumulated during the spreading season in a hawk-and-dove game. This co-evolutionary model …
