Spatially Extended SHAR Epidemiological Framework of Infectious Disease Transmission

Mathematical models play an important role in epidemiology. The inclusion of a spatial component in epidemiological models is especially important to understand and address many relevant ecological and public health questions, e.g., when wanting to differentiate transmission patterns across geographical regions or when considering spatially heterogeneous intervention measures. However, the introduction of spatial effects can have significant consequences on the observed model dynamics and hence must be carefully analyzed and interpreted. Cellular automata epidemiological models typically rely on simplified computational grids but can provide valuable insight into the spatial dynamics of transmission within a population by suitably accounting for the connections between individuals in the considered community. In this paper, we describe a stochastic cellular automata disease model based on an extension of the traditional Susceptible-Infected-Recovered (SIR) compartmentalization of the population, namely, the Susceptible-Hospitalized-Asymptomatic-Recovered (SHAR) formulation, in which infected individuals either present a severe form of the disease, thus requiring hospitalization, or belong to the so-called mild/asymptomatic class. The critical transmission threshold is derived analytically in the nonspatial SHAR formulation, and this generalizes previously obtained theoretical results for the SIR model. We present simulation results discussing the effect of key model parameters and of spatial correlations on model outputs and propose an algorithm for tracking the evolution of infection clusters within the considered population. Focusing on the role of import and criticality on the overall dynamics, we conclude that the current spatial setting increases the critical transmission threshold in comparison to the nonspatial model

A multiscale network-based model of contagion dynamics: heterogeneity, spatial distancing and vaccination

Lockdown and vaccination policies have been the major concern in the last year in order to contain the SARS-CoV-2 infection during the COVID-19 pandemic. In this paper we present a model able to evaluate alternative lockdown policies and vaccination strategies. Our approach integrates and refines the multiscale model proposed by Bellomo et al. , 2020, analyzing alternative network structures and bridging two perspectives to study complexity of living systems. Inside dierent matrices of contacts we explore the impact of closures of distinct nodes upon the overall contagion dynamics. Social distancing is shown to be more effective when targeting the reduction of contacts among and inside the most vulnerable nodes, namely hospitals/nursing homes. Moreover, our results suggest that school closures alone would not signicantly affect the infection dynamics and the number of deaths in the population. Finally, we investigate a scenario with immunization in order to understand the effectiveness of targeted vaccination policies towards the most vulnerable individuals. Our model agrees with the current proposed vaccination strategy prioritising the most vulnerable segment of the population to reduce deaths.Marie Sklodowska-Curie grant agreement No 79249

A Spatial Kinetic Model of Crowd Evacuation Dynamics with Infectious Disease Contagion

This paper proposes a kinetic theory approach coupling together the modeling of crowd evacuation from a bounded domain with exit doors and infectious disease contagion. The spatial movement of individuals in the crowd is modeled by a proper description of the interactions with people in the crowd and the environment, including walls and exits. At the same time, interactions among healthy and infectious individuals may generate disease spreading if exposure time is long enough. Immunization of the population and individual awareness to contagion is considered as well. Interactions are modeled by tools of game theory, that let us propose the so-called tables of games that are introduced in the general kinetic equations. The proposed model is qualitatively studied and, through a series of case studies, we explore different scenarios related to crowding and gathering formation within indoor venues under the spread of a respiratory infectious disease, obtaining insights on specific policies to reduce contagion that may be implemented

Understanding COVID-19 Epidemics: A Multi-Scale Modeling Approach

COVID-19 was declared a pandemic by the World Health Organization in March 2020 and, since then, research on mathematical modeling became imperative and very influential to understand the epidemiological dynamics of disease spreading and control under different scenarios. In this chapter, two different approaches to model the spread of COVID-19 are presented. The model frameworks are described and results are presented in connection with the current epidemiological situation of vaccination roll-out. This chapter is structured as follows. Section 2 presents the stochastic SHARUCD modeling framework developed within a modeling task force created to support public health managers during the COVID-19 crisis. As an extension of the basic SHAR (Susceptible-Hospitalized-Asymptomatic-Recovered) model, the SHARUCD models were parameterized and validated with empirical data for the Basque Country, Spain, and have been used (up until now) to monitor COVID-19 spreading and control over the course of the pandemic. Section 3 introduces the kinetic theory of active particles (KTAP) model for the spread of a disease. With an exploratory analysis, we present a possible way to deal with heterogeneity and multiscale features. Section 4 concludes this work, with a discussion on both models and further research perspectives description

Modeling dengue immune responses mediated by antibodies: A qualitative study

Dengue fever is a viral mosquito-borne infection and a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called antibody-dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: (i) primary dengue infection, (ii) secondary dengue infection with the same (homologous) dengue virus and (iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights into the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.A.S, H.F., and E.S. E.S. has received funded from the Indonesian RistekBrin Grant No. 122M/IT1.C02/TA.00/2021, 2021 (previously RistekDikti 2018-2021). M.A. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 792494

Modeling Dengue Immune Responses Mediated by Antibodies: Insights on the Biological Parameters to Describe Dengue Infections

Dengue fever is a viral mosquito-borne disease, a significant global health concern, with more than one third of the world population at risk of acquiring the disease. Caused by 4 antigenically distinct but related virus serotypes, named DENV-1, DENV-2, DENV-3, and DENV-4, infection by one serotype confers lifelong immunity to that serotype and a short period of temporary cross immunity to other related serotypes. Severe dengue is epidemiologically associated with a secondary infection caused by a heterologous serotype via the so-called antibody-dependent enhancement (ADE), an immunological process enhancing a new infection. Within-host dengue modeling is restricted to a small number of studies so far. With many open questions, the understanding of immunopathogenesis of severe disease during recurrent infections is important to evaluate the impact of newly licensed vaccines. In this paper, we revisit the modeling framework proposed by Sebayang et al. and perform a detailed sensitivity analysis of the well-known biological parameters and its possible combinations to understand the existing data sets. Using numerical simulations, we investigate features of viral replication, antibody production, and infection clearance over time for three possible scenarios: primary infection, secondary infection caused by homologous serotype, and secondary infection caused by heterologous serotype. Besides, describing well the infection dynamics as reported in the immunology literature, our results provide information on parameter combinations to best describe the differences on the immunological dynamics of secondary infections with homologous and heterologous viruses. The results presented here will be used as baseline to investigate a more complex within-host dengue model.Marie Skłodowska-Curie grant agreement No 79249

Critical fluctuations in epidemic models explain COVID‑19 post‑lockdown dynamics

As the COVID-19 pandemic progressed, research on mathematical modeling became imperative and very influential to understand the epidemiological dynamics of disease spreading. The momentary reproduction ratio r(t) of an epidemic is used as a public health guiding tool to evaluate the course of the epidemic, with the evolution of r(t) being the reasoning behind tightening and relaxing control measures over time. Here we investigate critical fluctuations around the epidemiological threshold, resembling new waves, even when the community disease transmission rate β is not signifcantly changing. Without loss of generality, we use simple models that can be treated analytically and results are applied to more complex models describing COVID-19 epidemics. Our analysis shows that, rather than the supercritical regime (infectivity larger than a critical value, β>βc) leading to new exponential growth of infection, the subcritical regime (infectivity smaller than a critical value, β<βc) with small import is able to explain the dynamic behaviour of COVID-19 spreading after a lockdown lifting, with r(t) ≈ 1 hovering around its threshold value.BMTF “Mathematical Modeling Applied to Health” Project European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 79249

What is life? A perspective of the mathematical kinetic theory of active particles

The modeling of living systems composed of many interacting entities is treated in this paper with the aim of describing their collective behaviors. The mathematical approach is developed within the general framework of the kinetic theory of active particles. The presentation is in three parts. First, we derive the mathematical tools, subsequently, we show how the method can be applied to a number of case studies related to well defined living systems, and finally, we look ahead to research perspectives

Seasonally Forced SIR Systems Applied to Respiratory Infectious Diseases, Bifurcations, and Chaos

We investigate models to describe respiratory diseases with fast mutating virus pathogens such that after some years the aquired resistance is lost and hosts can be infected with new variants of the pathogen. Such models were initially suggested for respiartory diseases like influenza, showing complex dynamics in reasonable parameter regions when comparing to historic empirical influenza like illness data, e.g., from Ille de France. The seasonal forcing typical for respiratory diseases gives rise to the different rich dynamical scenarios with even small parameter changes. Especially the seasonality of the infection leads for small values already to period doubling bifurcations into chaos, besides additional coexisting attractors. Such models could in the future also play a role in understanding the presently experienced COVID-19 pandemic, under emerging new variants and with only limited vaccine efficacies against newly upcoming variants. From first period doubling bifurcations, we can eventually infer at which close by parameter regions complex dynamics including deterministic chaos can arise.Marie Skłodowska-Curie grant agreement No. 79249

Mathematical models for dengue fever epidemiology: a 10-year systematic review

Mathematical models have a long history in epidemiological research, and as the COVID-19 pandemic progressed, research on mathematical modeling became imperative and very influential to understand the epidemiological dynamics of disease spreading. Mathematical models describing dengue fever epidemiological dynamics are found back from 1970. Dengue fever is a viral mosquito-borne infection caused by four antigenically related but distinct serotypes (DENV-1 to DENV-4). With 2.5 billion people at risk of acquiring the infection, it is a major international public health concern. Although most of the cases are asymptomatic or mild, the disease immunological response is complex, with severe disease linked to the antibody-dependent enhancement (ADE) - a disease augmentation phenomenon where pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection. Here, we present a 10-year systematic review on mathematical models for dengue fever epidemiology. Specifically, we review multi-strain frameworks describing host-to-host and vector-host transmission models and within-host models describing viral replication and the respective immune response. Following a detailed literature search in standard scientific databases, different mathematical models in terms of their scope, analytical approach and structural form, including model validation and parameter estimation using empirical data, are described and analysed. Aiming to identify a consensus on infectious diseases modeling aspects that can contribute to public health authorities for disease control, we revise the current understanding of epidemiological and immunological factors influencing the transmission dynamics of dengue. This review provide insights on general features to be considered to model aspects of real-world public health problems, such as the current epidemiological scenario we are living in.M. A. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 792494