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 R₀ 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 R₀ < 1, and the endemic equilibrium is globally asymptotically stable when R₀ > 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.     

Global stability of nonresident computer virus models

In this paper, applying Lyapunov functional techniques to nonresident computer virus models, we establish global dynamics of the model whose threshold parameter is the basic reproduction number R₀ such that the virus‐free equilibrium is globally asymptotically stable when R₀ ≤ 1, and the infected equilibrium is globally asymptotically stable when R₀ > 1 under the same restricted condition on a parameter, which appeared in the literature on delayed susceptible‐infected‐recovered‐susceptible (SIRS) epidemic models. We use new techniques on permanence and global stability of this model for R₀ > 1. Copyright © 2014 John Wiley & Sons, Ltd.     

HIV/AIDS epidemic fractional-order model

In this paper a non-linear mathematical model with fractional order ?, 0 < ? ≤ 1 is presented for analyzing and controlling the spread of HIV/AIDS. Both the disease-free equilibrium E₀ and the endemic equilibrium E^* are found and their stability is discussed using the stability theorem of fractional order differential equations. The basic reproduction number R₀ plays an essential role in the stability properties of our system. When R₀ < 1 the disease-free equilibrium E₀ is attractor, but when R₀ > 1, E₀ is unstable and the endemic equilibrium (EE) E^* exists and it is an attractor. Finally numerical Simulations are also established to investigate the influence of the system parameter on the spread of the disease.     

Within‐host and synaptic transmissions: contributions to the spread of HIV infection

We study the contributions of within‐host (virus‐to‐cell) and synaptic (cell‐to‐cell) transmissions in a mathematical model for human immunodeficiency virus epidemics. The model also includes drug resistance. We prove the local and global stability of the disease‐free equilibrium and the local stability of the endemic equilibrium. We analyse the effect of the cell‐to‐cell transmission rate on the value of the reproduction number, R₀. Moreover, we show evidence of a qualitative change in the models' dynamics, subjected to the value of the drug efficacy. In the end, important inferences are drawn. Copyright © 2016 John Wiley & Sons, Ltd.     

Bifurcation analysis of HIV infection model with antibody and cytotoxic T‐lymphocyte immune responses and Beddington–DeAngelis functional response

In this paper, a mathematical model for HIV‐1 infection with antibody, cytotoxic T‐lymphocyte immune responses and Beddington–DeAngelis functional response is investigated. The stability of the infection‐free and infected steady states is investigated. The basic reproduction number R₀ is identified for the proposed system. If R₀ < 1, then there is an infection‐free steady state, which is locally asymptotically stable. Further, the infected steady state is locally asymptotically stable for R₀ > 1 in the absence of immune response delay. We use Nyquist criterion to estimate the length of the delay for which stability continues to hold. Also the existence of the Hopf bifurcation is investigated by using immune response delay as a bifurcation parameter. Numerical simulations are presented to justify the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.     

Mathematical model for the dynamics of visceral leishmaniasis–malaria co‐infection

A mathematical model to understand the dynamics of malaria–visceral leishmaniasis co‐infection is proposed and analyzed. Results show that both diseases can be eliminated if R₀, the basic reproduction number of the co‐infection, is less than unity, and the system undergoes a backward bifurcation where an endemic equilibrium co‐exists with the disease‐free equilibrium when one of R_m or R_l, the basic reproduction numbers of malaria‐only and visceral leishmaniasis‐only, is precisely less than unity. Results also show that in the case of maximum protection against visceral leishmaniasis (VL), the disease‐free equilibrium is globally asymptotically stable if malaria patients are protected from VL infection; similarly, in the case of maximum protection against malaria, the disease‐free equilibrium is globally asymptotically stable if VL and post‐kala‐azar dermal leishmaniasis patients and the recovered humans after VL are protected from malaria infection. Numerical results show that if R_m and R_l are greater than unity, then we have co‐existence of both disease at an endemic equilibrium, and malaria incidence is higher than visceral leishmaniasis incidence at steady state. Copyright © 2016 John Wiley & Sons, Ltd.     

Spatial‐temporal basic reproduction number and dynamics for a dengue disease diffusion model

A reaction‐diffusion system with free boundary is proposed to describe the transmission of the dengue disease from mosquitoes to humans. In addition to the classical basic reproduction number R₀, the spatial‐temporal basic reproduction number is introduced to determine the persistence and eradication of the disease. Some sufficient conditions for the disease vanishing or spreading are obtained. The disease will go extinct under one of the conditions: the classical basic reproduction number R₀ < 1 and the spatial‐temporal basic reproduction number with small expanding capability. The spread of the disease in the whole area is possible if for some t≥0. Numerical simulations are also given to illustrate the theoretical results.     

Optimal control and sensitivity analysis of SIV→HIV dynamics with effects of infected immigrants in sub‐Saharan Africa

Regional migration has become an underlying factor in the spread of HIV transmission. In addition, immigrants with HIV status has contributed with high‐risk of sexually transmitted infection to its “destination” communities and promotes dissemination of HIV. Efforts to address HIV/AIDS among conflict‐affected populations should be properly addressed to eliminate potential role of the spread of the disease and risk of exposure to HIV. Motivated from this situation, HIV‐infected immigrants factor to HIV/SIV transmission link will be investigated in this research and examine its potential effect using optimal control method. Nonlinear deterministic mathematical model is used which is a multiple host model comprising of humans and chimpanzees. Some basic properties of the model such as invariant region and positivity of the solutions will be examined. The local stability of the disease‐free equilibrium was examined by computing the basic reproduction number, and it was found to be locally asymptotically stable when ?₀<1 and unstable otherwise. Sensitivity analysis was conducted to determine the parameters that help most in the spread of the virus. Pontryagin's maximum principle is used to obtain the optimality conditions for controlling the disease spread. Numerical simulation was conducted to obtain the analytical results. The results shows that combination of public health awareness, treatment, and culling help in controlling the HIV disease spread.     

Effect of partial immunity on transmission dynamics of dengue disease with optimal control

Dengue fever is one of the most dangerous vector‐borne diseases in the world in terms of death and economic cost. Hence, the modeling of dengue fever is of great significance to understand the dynamics of dengue. In this paper, we extend dengue disease transmission models by including transmit vaccinated class, in which a portion of recovered individual loses immunity and moves to the susceptibles with limited immunity and hence a less transmission probability. We obtain the threshold dynamics governed by the basic reproduction number R₀; it is shown that the disease‐free equilibrium is locally asymptotically stable if R₀ ≤ 1, and the system is uniformly persistence if R₀ > 1. We do sensitivity analysis in order to identify the key factors that greatly affect the dengue infection, and the partial rank correlation coefficient (PRCC) values for R₀ shows that the bitting rate is the most effective in lowering dengue new infections, and moreover, control of mosquito size plays an essential role in reducing equilibrium level of dengue infection. Hence, the public are highly suggested to control population size of mosquitoes and to use mosquito nets. By formulating the control objective, associated with the low infection and costs, we propose an optimal control question. By the application of optimal control theory, we analyze the existence of optimal control and obtain necessary conditions for optimal controls. Numerical simulations are carried out to show the effectiveness of control strategies; these simulations recommended that control measures such as protection from mosquito bites and mosquito eradication strategies effectively control and eradicate the dengue infections during the whole epidemic.     

Global dynamics of delay‐distributed HIV infection models with differential drug efficacy in cocirculating target cells

In this paper, we investigate the dynamical behaviors of three human immunodeficiency virus infection models with two types of cocirculating target cells and distributed intracellular delay. The models take into account both short‐lived infected cells and long‐lived chronically infected cells. In the two types of target cells, the drug efficacy is assumed to be different. The incidence rate of infection is given by bilinear and saturation functional responses in the first and second models, respectively, while it is given by a general function in the third model. Lyapunov functionals are constructed and LaSalle invariance principle is applied to prove the global asymptotic stability of all equilibria of the models. We have derived the basic reproduction number R₀ for the three models. For the first two models, we have proven that the disease‐free equilibrium is globally asymptotically stable (GAS) when R₀≤1, and the endemic equilibrium is GAS when R₀>1. For the third model, we have established a set of sufficient conditions for global stability of both equilibria of the model. We have checked our theoretical results with numerical simulations. Copyright © 2015 John Wiley & Sons, Ltd.     

Qualitative analysis of the SICR epidemic model with impulsive vaccinations

Control of epidemic infections is a very urgent issue today. To develop an appropriate strategy for vaccinations and effectively prevent the disease from arising and spreading, we proposed a modified Susceptible‐Infected‐Removed model with impulsive vaccinations. For the model without vaccinations, we proved global stability of one of the steady states depending on the basic reproduction number R₀. As typically in the epidemic models, the threshold value of R₀ is 1. If R₀ is greater than 1, then the positive steady state called endemic equilibrium exists and is globally stable, whereas for smaller values of R₀, it does not exist, and the semi‐trivial steady state called disease‐free equilibrium is globally stable. Using impulsive differential equation comparison theorem, we derived sufficient conditions under which the infectious disease described by the considered model disappears ultimately. The analytical results are illustrated by numerical simulations for Hepatitis B virus infection that confirm the theoretical possibility of the infection elimination because of the proper vaccinations policy. Copyright © 2012 John Wiley & Sons, Ltd.     

Modeling diseases with latency and nonlinear incidence rates: global dynamics of a multi‐group model

In this paper, we perform global stability analysis of a multi‐group SEIR epidemic model in which we can consider the heterogeneity of host population and the effects of latency and nonlinear incidence rates. For a simpler version that assumes an identical natural death rate for all groups, and with a gamma distribution for the latency, the basic reproduction number is defined by the theory of the next generation operator and proved to be a sharp threshold determining whether or not disease spread. Under certain assumptions, the disease‐free equilibrium is globally asymptotically stable if R₀≤1 and there exists a unique endemic equilibrium which is globally asymptotically stable if R₀>1. The proofs of global stability of equilibria exploit a matrix‐theoretic method using Perron eigenvetor, a graph‐theoretic method based on Kirchhoff's matrix tree theorem and Lyapunov functionals. Copyright © 2015 John Wiley & Sons, Ltd.     

Global dynamics of a multistage SIR model with distributed delays and nonlinear incidence rate

In this paper, a multistage susceptible‐infectious‐recovered model with distributed delays and nonlinear incidence rate is investigated, which extends the model considered by Guo et al. [H. Guo, M. Y. Li and Z. Shuai, Global dynamics of a general class of multistage models for infectious diseases, SIAM J. Appl. Math., 72 (2012), 261–279]. Under some appropriate and realistic conditions, the global dynamics is completely determined by the basic reproduction number R₀. If R₀≤1, then the infection‐free equilibrium is globally asymptotically stable and the disease dies out in all stages. If R₀>1, then a unique endemic equilibrium exists, and it is globally asymptotically stable, and hence the disease persists in all stages. The results are proved by utilizing the theory of non‐negative matrices, Lyapunov functionals, and the graph‐theoretical approach. Copyright © 2016 John Wiley & Sons, Ltd.     

Global dynamics of a Vector‐Borne disease model with two delays and nonlinear transmission rate

In this paper, we investigate a Vector‐Borne disease model with nonlinear incidence rate and 2 delays: One is the incubation period in the vectors and the other is the incubation period in the host. Under the biologically motivated assumptions, we show that the global dynamics are completely determined by the basic reproduction number R₀. The disease‐free equilibrium is globally asymptotically stable if R₀≤1; when R₀>1, the system is uniformly persistent, and there exists a unique endemic equilibrium that is globally asymptotically. Numerical simulations are conducted to illustrate the theoretical results.     

Global properties of a class of HIV infection models with Beddington–DeAngelis functional response

In this paper, the global properties of a class of human immunodeficiency virus (HIV) models with Beddington–DeAngelis functional response are investigated. Lyapunov functions are constructed to establish the global asymptotic stability of the uninfected and infected steady states of three HIV infection models. The first model considers the interaction process of the HIV and the CD4 ⁺ T cells and takes into account the latently and actively infected cells. The second model describes two co‐circulation populations of target cells, representing CD4 ⁺ T cells and macrophages. The third model is a two‐target‐cell model taking into account the latently and actively infected cells. We have proven that if the basic reproduction number R₀ is less than unity, then the uninfected steady state is globally asymptotically stable, and if R₀ > 1, then the infected steady state is globally asymptotically stable. Copyright © 2012 John Wiley & Sons, Ltd.     

Global dynamics of a intracellular infection model with delays and humoral immunity

A virus infection model with time delays and humoral immunity has been investigated. Mathematical analysis shows that the global dynamics of the model is fully determined by the basic reproduction numbers of the virus and the immune response, R₀ and R₁. The infection‐free equilibrium P₀ is globally asymptotically stable when R₀≤1. The infection equilibrium without immunity P₁ is globally asymptotically stable when R₁≤1 < R₀. The infection equilibrium with immunity P₂ is globally asymptotically stable when R₁>1. The expression of the basic reproduction number of the immune response R₁ implies that the immune response reduces the concentration of free virus as R₁>1. Copyright © 2016 John Wiley & Sons, Ltd.     

Global stability of multi-group SEIR epidemic models with distributed delays and nonlinear transmission

The dynamics of multi-group SEIR epidemic models with distributed and infinite delay and nonlinear transmission are investigated. We derive the basic reproduction number R₀ and establish that the global dynamics are completely determined by the values of R₀: if R₀≤1, then the disease-free equilibrium is globally asymptotically stable; if R₀>1, then there exists a unique endemic equilibrium which is globally asymptotically stable. Our results contain those for single-group SEIR models with distributed and infinite delays. In the proof of global stability of the endemic equilibrium, we exploit a graph-theoretical approach to the method of Lyapunov functionals. The biological significance of the results is also discussed.     

A class of delayed viral models with saturation infection rate and immune response

In this paper, a class of three delayed viral dynamics models with immune response and saturation infection rate are proposed and studied. By constructing suitable Lyapunov functionals, we derive the basic reproduction number R₀ and the corresponding immune response reproduction numbers for the viral infection models, and establish that the global dynamics are completely determined by the values of the related basic reproduction number and immune response reproduction numbers. Copyright © 2012 John Wiley & Sons, Ltd.     

Epidemic thresholds for infections in uncertain networks

Over the last 10 years, the field of mathematical epidemiology has piqued the interest of complex‐systems researchers, resulting in a tremendous volume of work exploring the effects of population structure on disease propagation. Much of this research focuses on computing epidemic threshold tests, and in practice several different tests are often used interchangeably. We summarize recent literature that attempts to clarify the relationships among different threshold criteria, systematize the incorporation of population structure into a general infection framework, and discuss conditions under which interaction topology and infection characteristics can be decoupled in the computation of the basic reproductive ratio, R₀. We then present methods for making predictions about disease spread when only partial information about the routes of transmission is available. These methods include approximation techniques and bounds obtained via spectral graph theory, and are applied to several data sets. © 2008 Wiley Periodicals, Inc. Complexity, 2009     

The global dynamics of a model about HIV-1 infection in vivo

A four dimension ODE model is built to study the infection of human immunodeficiency virus (HIV) in vivo. We include in this model four components: the healthy T cells, the latent-infected T cells, the active-infected T cells and the HIV virus. Two types of HIV transmissions in vivo are also included in the model: the virus-to-cell transmission, and the cell-to-cell HIV transmission. There are two possible equilibriums: the healthy equilibrium, and the infected steady state. The basic reproduction number R ₀ is introduced. When R ₀ < 1, the healthy equilibrium is globally stable and when R ₀ > 1, the infected equilibrium exists and is globally stable. Through simulations, we find that, the cell-to-cell HIV transmission is very important for the final outcome of the HIV attacking. Some important clinical observations about the HIV infection situation in lymph node are also verified.