Despite high vaccine coverage, pertussis has re-emerged as a public health concern in many countries. One hypothesis posed for re-emergence is the waning of immunity. In some disease systems, the process of waning immunity can be non-linear, involving a complex relationship between the duration of immunity and subsequent boosting of immunity through asymptomatic re-exposure.
We present and analyse a model of infectious disease transmission to examine the interplay between infection and immunity. By allowing the duration of infection-acquired immunity to differ from that of vaccine-acquired immunity, we explore the impact of the difference in durations on long-term disease patterns and prevalence of infection.
Our model demonstrates that vaccination may induce cyclic behaviour, and its ability to reduce the infection prevalence increases with both the duration of infection-acquired immunity and duration of vaccine-acquired immunity. We find that increasing vaccine coverage, while capable of leading to an increase in overall transmission, always results in a reduction in prevalence of primary infections, with epidemic cycles characterised by a longer interepidemic period and taller peaks.
Our results show that the epidemiological patterns of an infectious disease may change considerably when the duration of vaccine-acquired immunity differs from that of infection-acquired immunity. Our study highlights that for any particular disease and associated vaccine, a detailed understanding of the duration of protection and how that duration is influenced by infection prevalence is important as we seek to optimise vaccination strategies.
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 models capture transmission dynamics of infectious diseases for which immunity is not lifelong. Extending these models by a W compartment for individuals with waning immunity, the boosting of the immune system upon repeated exposure may be incorporated. Previous analyses assumed identical waning rates from R to W and from W to S. This implicitly assumes equal length for the period of full immunity and of waned immunity. We relax this restriction, and allow an asymmetric partitioning of the total immune period. Stability switches of the endemic equilibrium are investigated with a combinati…
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…
In more than two years since the COVID-19 virus was first detected in China, hundreds of millions of individuals have been infected, and millions have died. Aside from the immediate need for medical solutions (such as vaccines and medications) to treat the epidemic, the Corona pandemic has strengthened the demand for mathematical models that can predict the spread of the pandemic in an ever-changing reality. Here, we present a novel, dynamic particle model based on the basic principles of statistical physics that enables the prediction of the spreading of Covid-19 in the presence of effective …
Background: There is a lack of population-based studies on the effectiveness and durability of the SARS-CoV-2-induced immune protection during the Omicron wave. Methods: This retrospective study included 470 159 cases aged 60 years or older, who tested positive for SARS-CoV-2 between January 1 and June 30, 2022 in Bavaria, Germany. We examined time to death, measured from the earliest date of reporting/symptom onset until day 60. Cox models were used to estimate adjusted hazard ratios (HR) for sex, age, earliest calendar date of documented infection, and level of vaccine-induced or hybrid immu…
The COVID-19 pandemic has placed unprecedented demands on local public health units in Ontario, Canada, one of which was the need for in-house epidemiological-modelling capabilities. To address this need, Ontario Tech University and the Durham Region Health Department developed a native Windows desktop app that performs epidemiological modelling of infectious diseases. The app is an implementation of a multi-stratified compartmental epidemiological model that can accommodate multiple virus variants and levels of vaccination, as well as public health measures such as physical distancing, contac…
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 bacterium Group A Streptococcus (Streptococcus pyogenes, GAS) is a human-specific pathogen and a major cause of global morbidity and mortality. Despite decades of research our knowledge of GAS infection and immunity is incomplete, hampering vaccine design and other efforts to reduce disease prevalence. Epidemiological studies indicate positive associations between the prevalence of GAS-related disease, the diversity of circulating strains and the degree of poverty in host populations. However, the infection and immune mechanisms underlying these associations are not clear. In this work, we…
Seasonal influenza is a significant public health concern in the United States and globally. While influenza vaccines are the single most effective intervention to reduce influenza morbidity and mortality, there is considerable debate surrounding the merits and consequences of repeated seasonal vaccination. Here, we describe a two-season influenza epidemic contact network model and use it to demonstrate that increasing the level of continuity in vaccination across seasons reduces the burden on public health. We show that revaccination reduces the influenza attack rate not only because it reduc…
Dengue and Zika incidence data and the latest research have raised questions about how dengue vaccine strategies might be impacted by the emergence of Zika virus. Existing antibodies to one virus might temporarily protect or promote infection by the other through antibody-dependent enhancement (ADE). With this condition, understanding the dynamics of propagation of these two viruses is of great importance when implementing vaccines. In this work, we analyze the effect of vaccination against one strain, in a two-strain model that accounts for cross-immunity and ADE. Using basic and invasion rep…
There are often multiple diseases with cross immunity competing for vaccination resources. Here we investigate the optimal vaccination program in a two-layer Susceptible-Infected-Removed (SIR) model, where two diseases with cross immunity spread in the same population, and vaccines for both diseases are available. We identify three scenarios of the optimal vaccination program, which prevents the outbreaks of both diseases at the minimum cost. We analytically derive a criterion to specify the optimal program based on the costs for different vaccines.
The COVID-19 pandemic has severely impacted health systems and economies worldwide. Significant global efforts are therefore ongoing to improve vaccine efficacies, optimize vaccine deployment, and develop new antiviral therapies to combat the pandemic. Mechanistic viral dynamics and quantitative systems pharmacology models of SARS-CoV-2 infection, vaccines, immunomodulatory agents, and antiviral therapeutics have played a key role in advancing our understanding of SARS-CoV-2 pathogenesis and transmission, the interplay between innate and adaptive immunity to influence the outcomes of infection…
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 potential waning of the vaccination immunity to COVID-19 could pose threats to public health, as it is tenable that the timing of such waning would synchronize with the near-complete restoration of normalcy. Should also testing be relaxed, we might witness a resurgent COVID-19 wave in winter 2021/2022. In response to this risk, an additional vaccine dose, the booster shot, is being administered worldwide. In a projected study with an outlook of six months, we explore the interplay between the rate at which boosters are distributed and the extent to which testing practices are implemented, …
We introduce a novel compartmental model accounting for the effects of vaccine efficacy, deployment rates and timing of initiation of deployment. We simulate different scenarios and initial conditions, and we find that higher abundancy and rate of deployment of low efficacy vaccines lowers the cumulative number of deaths in comparison to slower deployment of high efficacy vaccines. We also forecast that, at the same daily deployment rate, the earlier introduction of vaccination schemes with lower efficacy would also lower the number of deaths with respect to a delayed introduction of high effi…
Using a simple economic model in which social-distancing reduces contagion, we study the implications of waning immunity for the epidemiological dynamics and social activity. If immunity wanes, we find that COVID-19 likely becomes endemic and that social-distancing is here to stay until the discovery of a vaccine or cure. But waning immunity does not necessarily change optimal actions on the onset of the pandemic. Decentralized equilibria are virtually independent of waning immunity until close to peak infections. For centralized equilibria, the relevance of waning immunity decreases in the pr…
This paper considers a mathematical model based on the transmission dynamics of hepatitis C virus (HCV) infection. In addition to the usual compartments for susceptible, exposed, and infected individuals, this model includes compartments for individuals who are under treatment and those who have had vaccination against HCV infection. It is assumed that the immunity provided by the vaccine fades with time. The basic reproduction number, $R_0$, and the equilibrium solutions of the model are determined. The model exhibits the phenomenon of backward bifurcation where a stable disease-free equilibr…
The success of a vaccination program is crucially dependent on its adoption by a critical fraction of the population, as the resulting herd immunity prevents future outbreaks of an epidemic. However, the effectiveness of a campaign can engender its own undoing if individuals choose to not get vaccinated in the belief that they are protected by herd immunity. Although this may appear to be an optimal decision, based on a rational appraisal of cost and benefits to the individual, it exposes the population to subsequent outbreaks. We investigate if voluntary vaccination can emerge in a an integra…
The Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), or Covid-19, burst into a pandemic in the beginning of 2020. An unprecedented worldwide effort involving academic institutions, regulatory agencies and industry is facing the challenges imposed by the rapidly spreading disease. Emergency use authorization for vaccines were granted in the beginning of December 2020 in Europe and nine days later in the United States. The urge for vaccination started a race, forcing governs and health care agencies to take decisions on the fly regarding the vaccination strategy and logistics. So f…
We have learned to live with many potentially deadly viruses for which there is no vaccine, no immunity, and no cure. We do not live in constant fear of these viruses, instead, we have learned how to outsmart them and reduce the harm they cause. A new mathematical model that combines the spread of diseases that do not confer immunity together with the evolution of human behaviors indicates that we may be able to fight new diseases with the same type of strategy we use to fight viruses like HIV.
We analyze an optimal control version of a simple SIRS epidemiology model. The policy maker can adopt policies to diminish the contact rate between infected and susceptible individuals, at a specific economic cost. The arrival of a vaccine will immediately end the epidemic. Total or partial immunity is modeled, while the contact rate can exhibit a (user specified) seasonality. The problem is solved in a spreadsheet environment. A reasonable parameter selection leads to optimal policies which are similar to those followed by different countries. A mild response relying on eventually reaching a …
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…
COVID-19 in low-tolerance border quarantine systems: impact of the Delta variant of SARS-CoV-2
The University of Melbourne（墨尔本大学）；Melbourne School of Population and Global Health, The University of Melbourne（墨尔本大学人口与全球健康学院）；The Peter Doherty Institute for Infection and Immunity, The Royal Melbourne Hospital and The University of Melbourne（彼得·多赫蒂感染与免疫研究所、皇家墨尔本医院和墨尔本大学）；Department of Infectious Diseases, The Alfred and Central Clinical School, Monash University（莫纳什大学阿尔弗雷德医院和中央临床学院传染病系）；School of Mathematics and Statistics, The University of Melbourne（墨尔本大学数学与统计学院）
The crisis caused by the COVID-19 outbreak around the globe raised an increasing concern about the ongoing emergence of variants of SARS-CoV-2 that may evade the immune response provided by vaccines. New variants appear due to mutation, and as the cases accumulate, the probability of the emergence of a variant of concern increases. In this article, we propose a modified SIR model with waning immunity that captures the competition of two strain classes of an infectious disease under the effect of vaccination with a highly contagious and deadly strain class emerging from a prior strain due to mu…
