Epidemiological data on seasonal influenza show that the growth rate of the number of infected individuals can increase passing from one exponential growth rate to another one with a larger exponent. Such behavior is not described by conventional epidemiological models. In this work an immuno-epidemiological model is proposed in order to describe this two-stage growth. It takes into account that the growth in the number of infected individuals increases the initial viral load and provides a passage from the first stage of epidemic where only people with weak immune response are infected to the second stage where people with strong immune response are also infected. This scenario may be viewed as an increase of the effective number of susceptible increasing the effective growth rate of infected.
Cholera, a severe gastrointestinal infection caused by the bacterium Vibrio cholerae, remains a major threat to public health with a yearly estimated global burden of 2.9 million cases. Although the majority of existing models for the disease focus on its population dynamics, it's important to link the multiple scales of the disease to gain better perspectives on its spread and control. In this study, we formulate an immuno-epidemiological model for cholera linking the between-host and within-host dynamics of the disease. The within-host model utilizes time-scale methods to differentiate the p…
Infection by distinct Dengue virus serotypes and host immunity are intricately linked. In particular, certain levels of cross-reactive antibodies in the host may actually enhance infection severity leading to Dengue hemorrhagic fever (DHF). The coupled immunological and epidemiological dynamics of Dengue calls for a multi-scale modeling approach. In this work, we formulate a within-host model which mechanistically recapitulates characteristics of antibody dependent enhancement (ADE) in Dengue infection. The within-host scale is then linked to epidemiological spread by a vector-host partial dif…
Sensitivity Analysis (SA) is a useful tool to measure the impact of changes in model parameters on the infection dynamics, particularly to quantify the expected efficacy of disease control strategies. SA has only been applied to epidemic models at the population level, ignoring the effect of within-host virus-with-immune-system interactions on the disease spread. Connecting the scales from individual to population can help inform drug and vaccine development. Thus the value of understanding the impact of immunological parameters on epidemiological quantities. Here we consider an age-since-infe…
The spread of infectious diseases is a major challenge in our contemporary world, especially after the recent outbreak of Coronavirus disease 2019 (COVID-19). The quarantine strategy is one of the important intervention measures to control the spread of an epidemic by greatly minimizing the likelihood of contact between infected and susceptible individuals. In this study, we analyze the impact of various stochastic disturbances on the epidemic dynamics during the quarantine period. For this purpose, we present an SIQS epidemic model that incorporates the stochastic transmission and the Lévy no…
One of the cornerstones in combating the HIV pandemic is being able to assess the current state and evolution of local HIV epidemics. This remains a complex problem, as many HIV infected individuals remain unaware of their infection status, leading to parts of HIV epidemics being undiagnosed and under-reported. To that end, we firstly present a method to learn epidemiological parameters from phylogenetic trees, using approximate Bayesian computation (ABC). The epidemiological parameters learned as a result of applying ABC are subsequently used in epidemiological models that aim to simulate a s…
A current challenge for disease modeling and public health is understanding pathogen dynamics across scales since their ecology and evolution ultimately operate on several coupled scales. This is particularly true for vector-borne diseases, where within-vector, within-host, and between vector-host populations all play crucial roles in diversity and distribution of the pathogen. Despite recent modeling efforts to determine the effect of within-host virus-immune response dynamics on between-host transmission, the role of within-vector viral dynamics on disease spread is overlooked. Here we formu…
A multi-scale immuno-epidemiological behavioral model for influenza-like illness: connecting scales through symptom scores
Mississippi State University（密西西比州立大学）；The University of Alabama in Huntsville（阿拉巴马大学亨茨维尔分校）；Florida Atlantic University（佛罗里达大西洋大学）；Texas Christian University（德克萨斯基督教大学）
The 2014 epidemic of the Ebola virus is governed by a genetically diverse viral population. In the early Sierra Leone outbreak, a recent study has identified new mutations that generate genetically distinct sequence clades. Here we find evidence that major Sierra Leone clades have systematic differences in growth rate and reproduction number. If this growth heterogeneity remains stable, it will generate major shifts in clade frequencies and influence the overall epidemic dynamics on time scales within the current outbreak. Our method is based on simple summary statistics of clade growth, which…
Estimation of epidemiological and population parameters from molecular sequence data has become central to the understanding of infectious disease dynamics. Various models have been proposed to infer details of the dynamics that describe epidemic progression. These include inference approaches derived from Kingman's coalescent theory. Here, we use recently described coalescent theory for epidemic dynamics to develop stochastic and deterministic coalescent SIR tree priors. We implement these in a Bayesian phylogenetic inference framework to permit joint estimation of SIR epidemic parameters and…
The reconstruction of phylogenetic trees based on viral genetic sequence data sequentially sampled from an epidemic provides estimates of the past transmission dynamics, by fitting epidemiological models to these trees. To our knowledge, none of the epidemiological models currently used in phylogenetics can account for recovery rates and sampling rates dependent on the time elapsed since transmission. Here we introduce an epidemiological model where infectives leave the epidemic, either by recovery or sampling, after some random time which may follow an arbitrary distribution. We derive an exp…
University of Minnesota（明尼苏达大学）；IQVIA（艾昆纬）；University of Virginia（弗吉尼亚大学）；Temple University（天普大学）；University of Illinois Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）
Accurate prediction of the transmission of epidemic diseases such as COVID-19 is crucial for implementing effective mitigation measures. In this work, we develop a tensor method to predict the evolution of epidemic trends for many regions simultaneously. We construct a 3-way spatio-temporal tensor (location, attribute, time) of case counts and propose a nonnegative tensor factorization with latent epidemiological model regularization named STELAR. Unlike standard tensor factorization methods which cannot predict slabs ahead, STELAR enables long-term prediction by incorporating latent temporal …
Harvard John A. Paulson School Of Engineering and Applied Sciences（哈佛大学约翰·A·保尔森工程与应用科学学院）；Harvard Medical School（哈佛医学院）；Harvard T.H. Chan School of Public Health（哈佛大学陈曾熙公共卫生学院）
Within epidemiological modeling, the majority of analyses assume a single epidemic process for generating ground-truth data. However, this assumed data generation process can be unrealistic, since data sources for epidemics are often aggregated across geographic regions and communities. As a result, state-of-the-art models for estimating epidemiological parameters, e.g.~transmission rates, can be inappropriate when faced with complex systems. Our work empirically demonstrates some limitations of applying epidemiological models to aggregated datasets. We generate three complex outbreak scenario…
The contact structure between hosts has a critical influence on disease spread. However, most networkbased models used in epidemiology tend to ignore heterogeneity in the weighting of contacts. This assumption is known to be at odds with the data for many contact networks (e.g. sexual contact networks) and to have a strong effect on the predictions of epidemiological models. One of the reasons why models usually ignore heterogeneity in transmission is that we currently lack tools to analyze weighted networks, such that most studies rely on numerical simulations. Here, we present a novel framew…
In this work, we review the figures used to characterize an epidemic outbreak most. Particular attention is drawn to epidemic spreading at time-varying transition rates. A time-varying SIR-like model is used to describe the epidemic dynamics, from which closed equations relating parameters and key quantities like reproduction ratio and doubling time are derived. The definition and computation of these metrics are revisited in the context of the general solution to the time-varying model dynamics, focusing on the similarities and differences with the time-invariant case. Further, the prediction…
Traditionally, the identification of parameters in the formulation and solution of inverse problems considers that models, variables and mathematical parameters are free of uncertainties. This aspect simplifies the estimation process, but does not consider the influence of relatively small changes in the design variables in terms of the objective function. In this work, the SIDR (Susceptible, Infected, Dead and Recovered) model is used to simulate the dynamic behavior of the novel coronavirus disease (COVID-19), and its parameters are estimated by formulating a robust inverse problem, that is,…
Contact patterns in populations fundamentally influence the spread of infectious diseases. Current mathematical methods for epidemiological forecasting on networks largely assume that contacts between individuals are fixed, at least for the duration of an outbreak. In reality, contact patterns may be quite fluid, with individuals frequently making and breaking social or sexual relationships. Here we develop a mathematical approach to predicting disease transmission on dynamic networks in which each individual has a characteristic behavior (typical contact number), but the identities of their c…
In this work we look at several mathematical models that have been constructed during the present pandemic to address dfferent issues of importance to public health policies about epidemic scenarios and thier causes. We start by briefly reviewing the most basic properties of the classic Kermack-McKendrick models and then proceed to look at some generalizations and their applications to contact structures, cocirculation of viral infections, growth patterns of epidemic curves, characterization of probability distributions and passage times necessary to parametrize the compartments that are added…
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 …
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…
We study the effects of switching social contacts as a strategy to control epidemic outbreaks. Connections between susceptible and infective individuals can be broken by either individual, and then reconnected to a randomly chosen member of the population. It is assumed that the reconnecting individual has no previous information on the epidemiological condition of the new contact. We show that reconnection can completely suppress the disease, both by continuous and discontinuous transitions between the endemic and the infection-free states. For diseases with an asymptomatic phase, we analyze …
Using digitized images of the three-dimensional, branching structures for root systems of bean seedlings, together with analytical and numerical methods that map a common 'SIR' epidemiological model onto the bond percolation problem, we show how the spatially-correlated branching structures of plant roots affect transmission efficiencies, and hence the invasion criterion, for a soil-borne pathogen as it spreads through ensembles of morphologically complex hosts. We conclude that the inherent heterogeneities in transmissibilities arising from correlations in the degrees of overlap between neigh…
In this paper, we estimate epidemiological data of the COVID-19 pandemic in Hungary using only the daily number of hospitalized patients, and applying well-known techniques from systems and control theory. We use a previously published and validated compartmental model for the description of epidemic spread. Exploiting the fact that an important subsystem of the model is linear, first we compute the number of latent infected persons in time. Then an estimate can be given for the number of people in other compartments. From these data, it is possible to track the time dependent reproduction num…
Several epidemiological models have been proposed to study the evolution of COVID-19 pandemic. In this paper, we propose an extension of the SUIHTER model, first introduced in [Parolini et al, Proc R. Soc. A., 2021] to analyse the COVID-19 spreading in Italy, which accounts for the vaccination campaign and the presence of new variants when they become dominant. In particular, the specific features of the variants (e.g. their increased transmission rate) and vaccines (e.g. their efficacy to prevent transmission, hospitalization and death) are modeled, based on clinical evidence. The new model i…
Bayesian Inference of Reproduction Number from Epidemiological and Genetic Data Using Particle MCMC
Nuffield Department of Medicine, University of Oxford（牛津大学纳菲尔德医学系）；School of Mathematics, Statistics and Physics, Newcastle University（纽卡斯尔大学数学、统计与物理学院）；Department of Statistics, University of Warwick（华威大学统计学系）；School of Life Sciences, University of Warwick（华威大学生命科学学院）；The Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research, University of Warwick（华威大学泽曼系统与传染病流行病学研究学院）
The evolution of RNA viruses such as HIV, Hepatitis C and Influenza virus occurs so rapidly that the viruses' genomes contain information on past ecological dynamics. Hence, we develop a phylodynamic method that enables the joint estimation of epidemiological parameters and phylogenetic history. Based on a compartmental susceptible-infected-removed (SIR) model, this method provides separate information on incidence and prevalence of infections. Detailed information on the interaction of host population dynamics and evolutionary history can inform decisions on how to contain or entirely avoid d…
Knowing the infection fatality ratio (IFR) is of crucial importance for evidence-based epidemic management: for immediate planning; for balancing the life years saved against the life years lost due to the consequences of management; and for evaluating the ethical issues associated with the tacit willingness to pay substantially more for life years lost to the epidemic, than for those to other diseases. Against this background Verity et al. (2020, Lancet Infections Diseases) have rapidly assembled case data and used statistical modelling to infer the IFR for COVID-19. We have attempted an in-d…
Understanding the spread of COVID-19 has been the subject of numerous studies, highlighting the significance of reliable epidemic models. Here, we introduce a novel epidemic model using a latent Hawkes process with temporal covariates for modelling the infections. Unlike other models, we model the reported cases via a probability distribution driven by the underlying Hawkes process. Modelling the infections via a Hawkes process allows us to estimate by whom an infected individual was infected. We propose a Kernel Density Particle Filter (KDPF) for inference of both latent cases and reproductio…
Epidemiological models contain a set of parameters that must be adjusted based on available observations. Once a model has been calibrated, it can be used as a forecasting tool to make predictions and to evaluate contingency plans. It is customary to employ only point estimators for such predictions. However, some models may fit the same data reasonably well for a broad range of parameter values, and this flexibility means that predictions stemming from such models will vary widely, depending on the particular parameter values employed within the range that give a good fit. When data are poor …
A feature often observed in epidemiological networks is significant heterogeneity in degree. A popular modelling approach to this has been to consider large populations with highly heterogeneous discrete contact rates. This paper defines an individual-level non-Markovian stochastic process that converges on standard ODE models of such populations in the appropriate asymptotic limit. A generalised Sellke construction is derived for this model, and this is then used to consider final outcomes in the case where heterogeneity follows a truncated Zipf distribution.
This paper is concerned with the design of intermittent non-pharmaceutical strategies to mitigate the spread of the COVID-19 epidemic exploiting network epidemiological models. Specifically, by studying a variational equation for the dynamics of the infected in a network model of the epidemic spread, we derive, using contractivity arguments, a condition that can be used to guarantee that, in epidemiological terms, the effective reproduction number is less than unity. This condition has three advantages: (i) it is easily computable; (ii) it is directly related to the model parameters; (iii) it …
Understanding individual decisions in a world where communications and information move instantly via cell phones and the internet, contributes to the development and implementation of policies aimed at stopping or ameliorating the spread of diseases. In this manuscript, the role of official social network perturbations generated by public health officials to slow down or stop a disease outbreak are studied over distinct classes of static social networks. The dynamics are stochastic in nature with individuals (nodes) being assigned fixed levels of education or wealth. Nodes may change their ep…
The COVID-19 epidemic is the last of a long list of pandemics that have affected humankind in the last century. In this paper, we propose a novel mathematical epidemiological model named SUIHTER from the names of the seven compartments that it comprises: susceptible uninfected individuals (S), undetected (both asymptomatic and symptomatic) infected (U), isolated (I), hospitalized (H), threatened (T), extinct (E), and recovered (R). A suitable parameter calibration that is based on the combined use of least squares method and Markov Chain Monte Carlo (MCMC) method is proposed with the aim of re…
During pandemic events, strategies such as social distancing can be fundamental to curb viral spreading. Such actions can reduce the number of simultaneous infections and mitigate the disease spreading, which is relevant to the risk of a healthcare system collapse. Although these strategies can be suggested, their actual implementation may depend on the population perception of the disease risk. The current COVID-19 crisis, for instance, is showing that some individuals are much more prone than others to remain isolated, avoiding unnecessary contacts. With this motivation, we propose an epidem…
IMT School for Advanced Studies Lucca（卢cca高等研究院）；TREE-TOWER S.R.L.（TREE-TOWER有限责任公司）
Computational models for the simulation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic evolution would be extremely useful to support authorities in designing healthcare policies and lockdown measures to contain its impact on public health and economy. In Italy, the devised forecasts have been mostly based on a pure data-driven approach, by fitting and extrapolating open data on the epidemic evolution collected by the Italian Civil Protection Center. In this respect, SIR epidemiological models, which start from the description of the nonlinear interactions between…
We present an epidemiological compartment model, SAIR(S), that explicitly captures the dynamics of asymptomatic infected individuals in an epidemic spread process. We first present a group model and then discuss networked versions. We provide an investigation of equilibria and stability properties for these models, and present simulation results illustrating the effects of asymptomatic-infected individuals on the spread of the disease. We also discuss local isolation effects on the epidemic dynamics in terms of the networked models. Finally, we provide initial parameter estimation results base…
In this paper, we propose a continuous-time stochastic intensity model, namely, two-phase dynamic contagion process(2P-DCP), for modelling the epidemic contagion of COVID-19 and investigating the lockdown effect based on the dynamic contagion model introduced by Dassios and Zhao (2011). It allows randomness to the infectivity of individuals rather than a constant reproduction number as assumed by standard models. Key epidemiological quantities, such as the distribution of final epidemic size and expected epidemic duration, are derived and estimated based on real data for various regions and co…
Phylodynamics is a set of population genetics tools that aim at reconstructing demographic history of a population based on molecular sequences of individuals sampled from the population of interest. One important task in phylodynamics is to estimate changes in (effective) population size. When applied to infectious disease sequences such estimation of population size trajectories can provide information about changes in the number of infections. To model changes in the number of infected individuals, current phylodynamic methods use non-parametric approaches, parametric approaches, and stocha…
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…
In this paper we study the susceptible-infectious (SI) epidemiological model using dynamical graphs. Dynamical structures have been recently applied in many areas including complex systems. Dynamical structures include the mutual interaction between the structure topology and the characteristics of its members. Dynamical graphs applied to epidemics consider generally that the nodes are individuals and the links represent different classes of relationships between individuals with the potential to transmit the disease. The main aim in this article is to study the evolution of the SI epidemiolog…
We consider a stochastic Susceptible-Exposed-Infected-Recovered (SEIR) epidemiological model with a contact rate that fluctuates seasonally. Through the use of a nonlinear, stochastic projection, we are able to analytically determine the lower dimensional manifold on which the deterministic and stochastic dynamics correctly interact. Our method produces a low dimensional stochastic model that captures the same timing of disease outbreak and the same amplitude and phase of recurrent behavior seen in the high dimensional model. Given seasonal epidemic data consisting of the number of infectious …
Inria（法国国家信息与自动化研究所）；Univ. de Bordeaux（波尔多大学）；Inserm（法国国家健康与医学研究院）；GREThA UMR 5113（应用理论经济学研究实验室（UMR 5113））；ENSTA ParisTech（巴黎高等先进技术学院）
Epidemiologists model the dynamics of epidemics in order to propose control strategies based on pharmaceutical and non-pharmaceutical interventions (contact limitation, lock down, vaccination, etc). Hand-designing such strategies is not trivial because of the number of possible interventions and the difficulty to predict long-term effects. This task can be cast as an optimization problem where state-of-the-art machine learning algorithms such as deep reinforcement learning, might bring significant value. However, the specificity of each domain -- epidemic modelling or solving optimization prob…
The evolution of epidemiological parameters, such as instantaneous reproduction number Rt, is important for understanding the transmission dynamics of infectious diseases. Current estimates of time-varying epidemiological parameters often face problems such as lagging observations, averaging inference, and improper quantification of uncertainties. To address these problems, we propose a Bayesian data assimilation framework for time-varying parameter estimation. Specifically, this framework is applied to Rt estimation, resulting in the state-of-the-art DARt system. With DARt, time misalignment …
Epidemiological processes are studied within a recently proposed hierarchical network model using the susceptible-infected-refractory dynamics of an epidemic. Within the network model, a population may be characterized by $H$ independent hierarchies or dimensions, each of which consists of groupings of individuals into layers of subgroups. Detailed numerical simulations reveal that for $H>1$, global spreading results regardless of the degree of homophily of the individuals forming a social circle. For H=1, a transition from global to local spread occurs as the population becomes decomposed int…
The COVID-19 pandemic started in Wuhan, China, and caused the worldwide spread of the RNA virus SARS-CoV-2, the causative agent of COVID-19. Because of its mutational rate, wide geographical distribution, and host response variance this coronavirus is currently evolving into an array of strains with increasing genetic diversity. Most variants apparently have neutral effects for disease spread and symptoms severity. However, in the viral Spike protein, which is responsible for host cell attachment and invasion, an emergent variant, containing the amino acid substitution D to G in position 614 (…
Epidemics like Covid-19 and Ebola have impacted people's lives significantly. The impact of mobility of people across the countries or states in the spread of epidemics has been significant. The spread of disease due to factors local to the population under consideration is termed the endogenous spread. The spread due to external factors like migration, mobility, etc. is called the exogenous spread. In this paper, we introduce the Exo-SIR model, an extension of the popular SIR model and a few variants of the model. The novelty in our model is that it captures both the exogenous and endogenous …
In this paper, we provide a straightforward approach to defining and deriving the key epidemiological quantity, the basic reproduction number, $R_0$, for Markovian epidemics in structured populations. The methodology derived is applicable to, and demonstrated on, both $SIR$ and $SIS$ epidemics and allows for population as well as epidemic dynamics. The approach taken is to consider the epidemic process as a multitype process by identifying and classifying the different types of infectious units along with the infections from, and the transitions between, infectious units. For the household mod…
