Long-Term Forecast of HIV/AIDS Epidemic in China with Fear Effect and 90-90-90 Strategies.

We formulate a compartmental model considering behavioral changes of susceptible individuals due to fear to assess the transmission dynamics of HIV/AIDS in mainland China. Stability and uniform persistence are analyzed. Markov chain Monte Carlo simulations and Latin hypercube sampling are used to estimate the basic reproduction number and its sensitivity to parameter variations. The estimated mean reproduction number is 1.2138 (95% CI 1.0834-1.3442). The basic reproduction numbers of aware susceptible individuals and high-risk susceptible individuals are [Formula: see text] (95% CI [Formula: see text]-[Formula: see text]) and 1.2138 (95% CI 1.0834-1.3442), respectively. Global sensitivity analysis shows that preventive measures are more effective than post-infection measures in eliminating the epidemic. We incorporate 90-90-90 strategies to predict the new HIV/AIDS cases in China in the next few decades, and the results show that it takes at least 26 years to achieve the goal of zero new HIV/AIDS cases.

Permanence via invasion graphs: incorporating community assembly into modern coexistence theory.

To understand the mechanisms underlying species coexistence, ecologists often study invasion growth rates of theoretical and data-driven models. These growth rates correspond to average per-capita growth rates of one species with respect to an ergodic measure supporting other species. In the ecological literature, coexistence often is equated with the invasion growth rates being positive. Intuitively, positive invasion growth rates ensure that species recover from being rare. To provide a mathematically rigorous framework for this approach, we prove theorems that answer two questions: (i) When do the signs of the invasion growth rates determine coexistence? (ii) When signs are sufficient, which invasion growth rates need to be positive? We focus on deterministic models and equate coexistence with permanence, i.e., a global attractor bounded away from extinction. For models satisfying certain technical assumptions, we introduce invasion graphs where vertices correspond to proper subsets of species (communities) supporting an ergodic measure and directed edges correspond to potential transitions between communities due to invasions by missing species. These directed edges are determined by the signs of invasion growth rates. When the invasion graph is acyclic (i.e. there is no sequence of invasions starting and ending at the same community), we show that permanence is determined by the signs of the invasion growth rates. In this case, permanence is characterized by the invasibility of all [Formula: see text] communities, i.e., communities without species i where all other missing species have negative invasion growth rates. To illustrate the applicability of the results, we show that dissipative Lotka-Volterra models generically satisfy our technical assumptions and computing their invasion graphs reduces to solving systems of linear equations. We also apply our results to models of competing species with pulsed resources or sharing a predator that exhibits switching behavior. Open problems for both deterministic and stochastic models are discussed. Our results highlight the importance of using concepts about community assembly to study coexistence.

Global dynamics of a generalist predator-prey model in open advective environments.

This paper deals with a system of reaction-diffusion-advection equations for a generalist predator-prey model in open advective environments, subject to an unidirectional flow. In contrast to the specialist predator-prey model, the dynamics of this system is more complex. It turns out that there exist some critical advection rates and predation rates, which classify the global dynamics of the generalist predator-prey system into three or four scenarios: (1) coexistence; (2) persistence of prey only; (3) persistence of predators only; and (4) extinction of both species. Moreover, the results reveal significant differences between the specialist predator-prey system and the generalist predator-prey system, including the evolution of the critical predation rates with respect to the ratio of the flow speeds; the take-over of the generalist predator; and the reduction in parameter range for the persistence of prey species alone. These findings may have important biological implications on the invasion of generalist predators in open advective environments.

Dynamics in a disease transmission model coupled virus infection in host with incubation delay and environmental effects.

In this paper, a disease transmission model coupled virus infection in host with incubation delay and environmental effects is studied. For the virus infection model in host with immune, latent delay and environmental virus invading, the threshold criteria on the global stability of antibody-free and antibody response infection equilibria are established. For the disease transmission model with incubation delay and immune response in host, basic reproduction number R 0 is defined, and the local stability of equilibria are established, i.e., the disease-free equilibrium is locally asymptotically stable if R 0 < 1 , and the endemic equilibrium is locally asymptotically stable if R 0 > 1 . Furthermore, the uniform persistence of positive solutions is studied while there is not the direct transmission of disease by the infected individuals. Finally, the numerical examples are presented to verify the main results.

Modelling the effects of the contaminated environments on tuberculosis in Jiangsu, China.

Tuberculosis (TB) is still an important public health issue in Jiangsu province, China. In this study, based on the TB transmission routes and the statistical data of TB cases, we formulate a novel TB epidemic model accounting for the effects of the contaminated environments on TB transmission dynamics. The value of this study lies in two aspects. Mathematically, we define the basic reproduction number, R0, and prove that R0 can be used to govern the threshold dynamics of the model. Epidemiologically, we find that the annual average R0 is 1.13,>1 and TB in Jiangsu is an endemic disease. Therefore, in order to control the TB in Jiangsu efficiently, we must decrease the virus shedding rate or increase the recovery rates, and increase the environmental clearance rate.

Threshold Dynamics in a Model for Zika Virus Disease with Seasonality.

We present a compartmental population model for the spread of Zika virus disease including sexual and vectorial transmission as well as asymptomatic carriers. We apply a non-autonomous model with time-dependent mosquito birth, death and biting rates to integrate the impact of the periodicity of weather on the spread of Zika. We define the basic reproduction number [Formula: see text] as the spectral radius of a linear integral operator and show that the global dynamics is determined by this threshold parameter: If [Formula: see text] then the disease-free periodic solution is globally asymptotically stable, while if [Formula: see text] then the disease persists. We show numerical examples to study what kind of parameter changes might lead to a periodic recurrence of Zika.

A delay model for persistent viral infections in replicating cells.

Persistently infecting viruses remain within infected cells for a prolonged period of time without killing the cells and can reproduce via budding virus particles or passing on to daughter cells after division. The ability for populations of infected cells to be long-lived and replicate viral progeny through cell division may be critical for virus survival in examples such as HIV latent reservoirs, tumor oncolytic virotherapy, and non-virulent phages in microbial hosts. We consider a model for persistent viral infection within a replicating cell population with time delay in the eclipse stage prior to infected cell replicative form. We obtain reproduction numbers that provide criteria for the existence and stability of the equilibria of the system and provide bifurcation diagrams illustrating transcritical (backward and forward), saddle-node, and Hopf bifurcations, and provide evidence of homoclinic bifurcations and a Bogdanov-Takens bifurcation. We investigate the possibility of long term survival of the infection (represented by chronically infected cells and free virus) in the cell population by using the mathematical concept of robust uniform persistence. Using numerical continuation software with parameter values estimated from phage-microbe systems, we obtain two parameter bifurcation diagrams that divide parameter space into regions with different dynamical outcomes. We thus investigate how varying different parameters, including how the time spent in the eclipse phase, can influence whether or not the virus survives.

Discrete-time population dynamics of spatially distributed semelparous two-sex populations.

Spatially distributed populations with two sexes may face the problem that males and females concentrate in different parts of the habitat and mating and reproduction does not happen sufficiently often for the population to persist. For simplicity, to explore the impact of sex-dependent dispersal on population survival, we consider a discrete-time model for a semelparous population where individuals reproduce only once in their life-time, during a very short reproduction season. The dispersal of females and males is modeled by Feller kernels and the mating by a homogeneous pair formation function. The spectral radius of a homogeneous operator is established as basic reproduction number of the population, [Formula: see text]. If [Formula: see text], the extinction state is locally stable, and if [Formula: see text] the population shows various degrees of persistence that depend on the irreducibility properties of the dispersal kernels. Special cases exhibit how sex-biased dispersal affects the persistence of the population.

Computational modeling of human papillomavirus with impulsive vaccination.

In this study, a new SIVS epidemic model for human papillomavirus (HPV) is proposed. The global dynamics of the proposed model are analyzed under pulse vaccination for the susceptible unvaccinated females and males. The threshold value for the disease-free periodic solution is obtained using the comparison theory for ordinary differential equations. It is demonstrated that the disease-free periodic solution is globally stable if the reproduction number is less than unity under some defined parameters. Moreover, we found the critical value of the pulse vaccination for susceptible females needed to control the HPV. The uniform persistence of the disease for some parameter values is also analyzed. The numerical simulations conducted agreed with the theoretical findings. It is found out using numerical simulation that the pulse vaccination has a good impact on reducing the disease.

Uniform persistence in a prey-predator model with a diseased predator.

Following the well-extablished mathematical approach to persistence and its developments contained in Rebelo et al. (Discrete Contin Dyn Syst Ser B 19(4):1155-1170. https://doi.org/10.3934/dcdsb.2014.19.1155, 2014) we give a rigorous theoretical explanation to the numerical results obtained in Bate and Hilker (J Theoret Biol 316:1-8. https://doi.org/10.3934/dcdsb.2014.19.1155, 2013) on a prey-predator Rosenzweig-MacArthur model with functional response of Holling type II, resulting in a cyclic system that is locally unstable, equipped with an infectious disease in the predator population. The proof relies on some repelling conditions that can be applied in an iterative way on a suitable decomposition of the boundary. A full stability analysis is developed, showing how the "invasion condition" for the disease is derived. Some in-depth conclusions and possible further investigations are discussed.

Invasion analysis on a predator-prey system in open advective environments.

We investigate a reaction-diffusion-advection system which characterizes the interactions between the predator and prey in advective environments, such as streams or rivers. In contrast with non-advective environments, the dynamics of this system is more complicated. It turns out that there exists a critical mortality rate of the predator and two critical advection rates, which classify the dynamic behavior of this system into two or three scenarios, that is, (i) both populations go extinct; (ii) the predator can not invade and the prey survives in the long run; (iii) the predator can invade successfully when rare and it will coexist permanently with the prey. Specially, the predator can invade successfully when rare if both the mortality rate of the predator and the advection rate are suitably small. Furthermore, by the global bifurcation theory and some auxiliary techniques, the existence and uniqueness of coexistence steady states of this system are established. Finally, by means of numerical simulations, the effects of diffusion on the dynamics of this system are investigated. The numerical results show that the random dispersals of both populations favor the invasion of the predator.

Global analysis of an environmental disease transmission model linking within-host and between-host dynamics.

In this paper, a multi-scale mathematical model for environmentally transmitted diseases is proposed which couples the pathogen-immune interaction inside the human body with the disease transmission at the population level. The model is based on the nested approach that incorporates the infection-age-structured immunological dynamics into an epidemiological system structured by the chronological time, the infection age and the vaccination age. We conduct detailed analysis for both the within-host and between-host disease dynamics. Particularly, we derive the basic reproduction number R 0 for the between-host model and prove the uniform persistence of the system. Furthermore, using carefully constructed Lyapunov functions, we establish threshold-type results regarding the global dynamics of the between-host system: the disease-free equilibrium is globally asymptotically stable when R 0 < 1, and the endemic equilibrium is globally asymptotically stable when R 0 > 1. We explore the connection between the within-host and between-host dynamics through both mathematical analysis and numerical simulation. We show that the pathogen load and immune strength at the individual level contribute to the disease transmission and spread at the population level. We also find that, although the between-host transmission risk correlates positively with the within-host pathogen load, there is no simple monotonic relationship between the disease prevalence and the individual pathogen load.

Asymptotic State of a Two-Patch System with Infinite Diffusion.

Mathematical theory has predicted that populations diffusing in heterogeneous environments can reach larger total size than when not diffusing. This prediction was tested in a recent experiment, which leads to extension of the previous theory to consumer-resource systems with external resource input. This paper studies a two-patch model with diffusion that characterizes the experiment. Solutions of the model are shown to be nonnegative and bounded, and global dynamics of the subsystems are completely exhibited. It is shown that there exist stable positive equilibria as the diffusion rate is large, and the equilibria converge to a unique positive point as the diffusion tends to infinity. Rigorous analysis on the model demonstrates that homogeneously distributed resources support larger carrying capacity than heterogeneously distributed resources with or without diffusion, which coincides with experimental observations but refutes previous theory. It is shown that spatial diffusion increases total equilibrium population abundance in heterogeneous environments, which coincides with real data and previous theory while a new insight is exhibited. A novel prediction of this work is that these results hold even with source-sink populations and increasing diffusion rate of consumer could change its persistence to extinction in the same-resource environments.

A periodic SEIRS epidemic model with a time-dependent latent period.

Many infectious diseases have seasonal trends and exhibit variable periods of peak seasonality. Understanding the population dynamics due to seasonal changes becomes very important for predicting and controlling disease transmission risks. In order to investigate the impact of time-dependent delays on disease control, we propose an SEIRS epidemic model with a periodic latent period. We introduce the basic reproduction ratio [Formula: see text] for this model and establish a threshold type result on its global dynamics in terms of [Formula: see text]. More precisely, we show that the disease-free periodic solution is globally attractive if [Formula: see text]; while the system admits a positive periodic solution and the disease is uniformly persistent if [Formula: see text]. Numerical simulations are also carried out to illustrate the analytic results. In addition, we find that the use of the temporal average of the periodic delay may underestimate or overestimate the real value of [Formula: see text].

A periodic two-patch SIS model with time delay and transport-related infection.

In this paper, we propose a periodic SIS epidemic model with time delay and transport-related infection in a patchy environment. The basic reproduction number R0 is derived which determines the global dynamics of the model system: if R0 < 1, the disease-free periodic state is globally attractive while there exists at least one positive periodic state and the disease persists if R0 > 1. Numerical simulations are performed to confirm the analytical results and to explore the dependence of R0 on the transport-related infection parameters and the amplitude of fluctuations.

Dynamics of virus and immune response in multi-epitope network.

The host immune response can often efficiently suppress a virus infection, which may lead to selection for immune-resistant viral variants within the host. For example, during HIV infection, an array of CTL immune response populations recognize specific epitopes (viral proteins) presented on the surface of infected cells to effectively mediate their killing. However HIV can rapidly evolve resistance to CTL attack at different epitopes, inducing a dynamic network of interacting viral and immune response variants. We consider models for the network of virus and immune response populations, consisting of Lotka-Volterra-like systems of ordinary differential equations. Stability of feasible equilibria and corresponding uniform persistence of distinct variants are characterized via a Lyapunov function. We specialize the model to a "binary sequence" setting, where for n epitopes there can be [Formula: see text] distinct viral variants mapped on a hypercube graph. The dynamics in several cases are analyzed and sharp polychotomies are derived characterizing persistent variants. In particular, we prove that if the viral fitness costs for gaining resistance to each epitope are equal, then the system of [Formula: see text] virus strains converges to a "perfectly nested network" with less than or equal to [Formula: see text] persistent virus strains. Overall, our results suggest that immunodominance, i.e. relative strength of immune response to an epitope, is the most important factor determining the persistent network structure.

Mathematical Analysis of an SIQR Influenza Model with Imperfect Quarantine.

The identification of mechanisms responsible for recurrent epidemic outbreaks, such as age structure, cross-immunity and variable delays in the infective classes, has challenged and fascinated epidemiologists and mathematicians alike. This paper addresses, motivated by mathematical work on influenza models, the impact of imperfect quarantine on the dynamics of SIR-type models. A susceptible-infectious-quarantine-recovered (SIQR) model is formulated with quarantined individuals altering the transmission dynamics process through their possibly reduced ability to generate secondary cases of infection. Mathematical and numerical analyses of the model of the equilibria and their stability have been carried out. Uniform persistence of the model has been established. Numerical simulations show that the model supports Hopf bifurcation as a function of the values of the quarantine effectiveness and other parameters. The upshot of this work is somewhat surprising since it is shown that SIQR model oscillatory behavior, as shown by multiple researchers, is in fact not robust to perturbations in the quarantine regime.

Global properties of nested network model with application to multi-epitope HIV/CTL dynamics.

Mathematical modeling and analysis can provide insight on the dynamics of ecosystems which maintain biodiversity in the face of competitive and prey-predator interactions. Of primary interests are the underlying structure and features which stabilize diverse ecological networks. Recently Korytowski and Smith (Theor Ecol 8(1):111-120, 2015) proved that a perfectly nested infection network, along with appropriate life history trade-offs, leads to coexistence and persistence of bacteria-phage communities in a chemostat model. In this article, we generalize their model in order to apply it to the within-host dynamics virus and immune response, in particular HIV and CTL (Cytotoxic T Lymphocyte) cells. Our model can describe sequential viral escape from dominant immune responses and rise in subdominant immune responses, consistent with observed patterns of HIV/CTL evolution. We find a Lyapunov function for the system which leads to rigorous characterization of persistent viral and immune variants, along with informing upon equilibria stability and global dynamics. Results are interpreted in the context of within-host HIV/CTL evolution and numerical simulations are provided.

Improved uniform persistence for partially diffusive models of infectious diseases: cases of avian influenza and Ebola virus disease.

Past works on partially diffusive models of diseases typically rely on a strong assumption regarding the initial data of their infection-related compartments in order to demonstrate uniform persistence in the case that the basic reproduction number $ \mathcal{R}_0 $ is above 1. Such a model for avian influenza was proposed, and its uniform persistence was proven for the case $ \mathcal{R}_0 > 1 $ when all of the infected bird population, recovered bird population and virus concentration in water do not initially vanish. Similarly, a work regarding a model of the Ebola virus disease required that the infected human population does not initially vanish to show an analogous result. We introduce a modification on the standard method of proving uniform persistence, extending both of these results by weakening their respective assumptions to requiring that only one (rather than all) infection-related compartment is initially non-vanishing. That is, we show that, given $ \mathcal{R}_0 > 1 $, if either the infected bird population or the viral concentration are initially nonzero anywhere in the case of avian influenza, or if any of the infected human population, viral concentration or population of deceased individuals who are under care are initially nonzero anywhere in the case of the Ebola virus disease, then their respective models predict uniform persistence. The difficulty which we overcome here is the lack of diffusion, and hence the inability to apply the minimum principle, in the equations of the avian influenza virus concentration in water and of the population of the individuals deceased due to the Ebola virus disease who are still in the process of caring.

Dynamics of a reaction-diffusion SIRS model with general incidence rate in a heterogeneous environment.

In this paper, we study a diffusive SIRS-type epidemic model with transfer from the infectious to the susceptible class. Our model includes a general nonlinear incidence rate and spatially heterogeneous diffusion coefficients. We compute the basic reproduction number R 0 of our model and establish the global stability of the disease-free steady state when R 0 < 1 . Furthermore, we study the uniform persistence when R 0 > 1 and perform a bifurcation analysis for a special case of our model. Some numerical simulations are presented to illustrate the dynamics of the solutions as the model parameters are varied.