Endemic threshold results in an age-duration-structured population model for HIV infection

In this paper we consider an age-duration-structured population model for HIV infection in a homosexual community. First we investigate the invasion problem to establish the basic reproduction ratio R(0) for the HIV/AIDS epidemic by which we can state the threshold criteria: The disease can invade into the completely susceptible population if R(0)>1, whereas it cannot if R(0)<1. Subsequently, we examine existence and uniqueness of endemic steady states. We will show sufficient conditions for a backward or a forward bifurcation to occur when the basic reproduction ratio crosses unity. That is, in contrast with classical epidemic models, for our HIV model there could exist multiple endemic steady states even if R(0) is less than one. Finally, we show sufficient conditions for the local stability of the endemic steady states.     

Numerical bifurcation analysis of the pattern formation in a cell based auxin transport model

Transport models of growth hormones can be used to reproduce the hormone accumulations that occur in plant organs. Mostly, these accumulation patterns are calculated using time step methods, even though only the resulting steady state patterns of the model are of interest. We examine the steady state solutions of the hormone transport model of Smith et al. (Proc Natl Acad Sci USA 103(5):1301–1306, 2006) for a one-dimensional row of plant cells. We search for the steady state solutions as a function of three of the model parameters by using numerical continuation methods and bifurcation analysis. These methods are more adequate for solving steady state problems than time step methods. We discuss a trivial solution where the concentrations of hormones are equal in all cells and examine its stability region. We identify two generic bifurcation scenarios through which the trivial solution loses its stability. The trivial solution becomes either a steady state pattern with regular spaced peaks or a pattern where the concentration is periodic in time.     

A mathematical model for Chagas disease with infection-age-dependent infectivity

In this paper we develop a mathematical model for Chagas disease with infection-age-dependent infectivity. The effects of vector and blood transfusion transmission are considered, and the infected population is structured by the infection age (the time elapsed from infection). The authors identify the basic reproduction ratio R0 and show that the disease can invade into the susceptible population and unique endemic steady state exists if R0 > 1, whereas the disease dies out if R0 is small enough. We show that depending on parameters, backward bifurcation of endemic steady state can occur, so even if R0 < 1, there could exist endemic steady states. We also discuss local and global stability of steady states.     

Analysis of a nonlinear diffusion problem With Michaelis-Menten kinetics by an integral equation method

A mathematical model for oxygen diffusion in a spherical cell with Michaelis-Menten oxygen uptake kinetics is analyzed by means of an intergral equation method. It is shown that an integral equation formulation can be used to obtain a numerical solution associated with this boundary and initial value problem. Through an illustrative numerical calculation we are able to obtain an accurate solution for both the steady and transient problems. Finally, a comparison is made with the numerical solution of McElwain and the variational solution of Anderson and Arthurs for the steady state and Lin's result concerning the unsteady state.     

Global dynamics of an epidemiological model with age of infection and disease relapse

In this paper, an epidemiological model with age of infection and disease relapse is investigated. The basic reproduction number for the model is identified, and it is shown to be a sharp threshold to completely determine the global dynamics of the model. By analysing the corresponding characteristic equations, the local stability of a disease-free steady state and an endemic steady state of the model is established. By means of suitable Lyapunov functionals and LaSalle's invariance principle, it is verified that if the basic reproduction number is less than unity, the disease-free steady state is globally asymptotically stable, and hence the disease dies out; if the basic reproduction number is greater than unity, the endemic steady state is globally asymptotically stable and the disease becomes endemic.     

Oscillatory phenomena in a model of infectious diseases

Oscillations of the number of cases around an average endemic level are common in several infectious diseases. In this paper we study simple deterministic models, where the oscillations arise either solely from periodically varying contact rates or from the combined effect of large initial perturbation, small periodic variation of the contact rate, and the destabilizing nature of infectious and latent periods when described as time delays. The main results are: (a) For a model with a periodically varying contact rate and a recovery rate, a threshold amplitude of variation is found by numerical and analytic methods at which 2-year subharmonic resonance appears. (b) Approximate analytic relationships are derived for the amplitude and phase of the forced 1-year oscillations below this threshold and for the 2-year oscillations above it—in terms of the reproduction rate of the infection. (c) Similar calculations are performed when the recovery rate is replaced by a fixed infectious period represented by a pure time delay. The threshold amplitude of variation in the contact rate is found here to be smaller than in the recovery rate model. (d) A model with a fixed infectious period and a constant contact rate is considered. The nontrivial steady state is shown to be locally stable for the parameter range of interest. However, the ratio of the imaginary to real parts of the eigenvalues in the characteristic equation is increased as compared to the corresponding model with a recovery rate. (e) For the model with a fixed infectious period and a constant contact rate an approximation method indicates consistency in a certain range of contact rates with the existence of an unstable periodic solution about the locally stable steady state. The actual existence of such a solution is not verified. The interpretation is that the destabilizing effect of the introduction of a pure delay into the model becomes more significant as the distance in the variables space from the endemic steady state is increased. (f) For a fixed infectious period and very small subthreshold variation in the contact rate, two different types of solutions are found numerically: yearly small-amplitude oscillations about an endemic average and large-amplitude oscillations of a subharmonic period. The pattern seen depends on the initial conditions. For a sufficiently large initial deviation from the endemic level even very small seasonal variations lead to regular recurrent outbreaks of the disease. The effect of latent periods and of changing the form of the interaction are also considered.     

Numerical bifurcation analysis of delay differential equations arising from physiological modeling

This paper has a dual purpose. First, we describe numerical methods for continuation and bifurcation analysis of steady state solutions and periodic solutions of systems of delay differential equations with an arbitrary number of fixed, discrete delays. Second, we demonstrate how these methods can be used to obtain insight into complex biological regulatory systems in which interactions occur with time delays: for this, we consider a system of two equations for the plasma glucose and insulin concentrations in a diabetic patient subject to a system of external assistance. The model has two delays: the technological delay of the external system, and the physiological delay of the patient's liver. We compute stability of the steady state solution as a function of two parameters, compare with analytical results and compute several branches of periodic solutions and their stability. These numerical results allow to infer two categories of diabetic patients for which the external system has different efficiency.     

An SIR epidemic model with partial temporary immunity modeled with delay

The SIR epidemic model for disease dynamics considers recovered individuals to be permanently immune, while the SIS epidemic model considers recovered individuals to be immediately resusceptible. We study the case of temporary immunity in an SIR-based model with delayed coupling between the susceptible and removed classes, which results in a coupled set of delay differential equations. We find conditions for which the endemic steady state becomes unstable to periodic outbreaks. We then use analytical and numerical bifurcation analysis to describe how the severity and period of the outbreaks depend on the model parameters.      

A stability analysis of the power-law steady state of marine size spectra

This paper investigates the stability of the power-law steady state often observed in marine ecosystems. Three dynamical systems are considered, describing the abundance of organisms as a function of body mass and time: a “jump-growth” equation, a first order approximation which is the widely used McKendrick–von Foerster equation, and a second order approximation which is the McKendrick–von Foerster equation with a diffusion term. All of these yield a power-law steady state. We derive, for the first time, the eigenvalue spectrum for the linearised evolution operator, under certain constraints on the parameters. This provides new knowledge of the stability properties of the power-law steady state. It is shown analytically that the steady state of the McKendrick–von Foerster equation without the diffusion term is always unstable. Furthermore, numerical plots show that eigenvalue spectra of the McKendrick–von Foerster equation with diffusion give a good approximation to those of the jump-growth equation. The steady state is more likely to be stable with a low preferred predator:prey mass ratio, a large diet breadth and a high feeding efficiency. The effects of demographic stochasticity are also investigated and it is concluded that these are likely to be small in real systems.     

Instability of the steady state solution in cell cycle population structure models with feedback

We show that when cell–cell feedback is added to a model of the cell cycle for a large population of cells, then instability of the steady state solution occurs in many cases. We show this in the context of a generic agent-based ODE model. If the feedback is positive, then instability of the steady state solution is proved for all parameter values except for a small set on the boundary of parameter space. For negative feedback we prove instability for half the parameter space. We also show by example that instability in the other half may be proved on a case by case basis.

     

Analysis of operating principles with S-system models

Operating principles address general questions regarding the response dynamics of biological systems as we observe or hypothesize them, in comparison to a priori equally valid alternatives. In analogy to design principles, the question arises: Why are some operating strategies encountered more frequently than others and in what sense might they be superior? It is at this point impossible to study operation principles in complete generality, but the work here discusses the important situation where a biological system must shift operation from its normal steady state to a new steady state. This situation is quite common and includes many stress responses. We present two distinct methods for determining different solutions to this task of achieving a new target steady state. Both methods utilize the property of S-system models within Biochemical Systems Theory (BST) that steady states can be explicitly represented as systems of linear algebraic equations. The first method uses matrix inversion, a pseudo-inverse, or regression to characterize the entire admissible solution space. Operations on the basis of the solution space permit modest alterations of the transients toward the target steady state. The second method uses standard or mixed integer linear programming to determine admissible solutions that satisfy criteria of functional effectiveness, which are specified beforehand. As an illustration, we use both methods to characterize alternative response patterns of yeast subjected to heat stress, and compare them with observations from the literature.     

Diseases with chronic stage in a population with varying size

An epidemiological model of hepatitis C with a chronic infectious stage and variable population size is introduced. A non-structured baseline ODE model which supports exponential solutions is discussed. The normalized version where the unknown functions are the proportions of the susceptible, infected, and chronic individuals in the total population is analyzed. It is shown that sustained oscillations are not possible and the endemic proportions either approach the disease-free or an endemic equilibrium. The expanded model incorporates the chronic age of the individuals. Partial analysis of this age-structured model is carried out. The global asymptotic stability of the infection-free state is established as well as local asymptotic stability of the endemic non-uniform steady state distribution under some additional conditions. A numerical method for the chronic-age-structured model is introduced. It is shown that this numerical scheme is consistent and convergent of first order. Simulations based on the numerical method suggest that in the structured case the endemic equilibrium may be unstable and sustained oscillations are possible. Closer look at the reproduction number reveals that treatment strategies directed towards speeding up the transition from acute to chronic stage in effect contribute to the eradication of the disease.     

Travelling waves of a delayed SIR epidemic model with nonlinear incidence rate and spatial diffusion

This paper is concerned with the existence of travelling waves to a SIR epidemic model with nonlinear incidence rate, spatial diffusion and time delay. By analyzing the corresponding characteristic equations, the local stability of a disease-free steady state and an endemic steady state to this system under homogeneous Neumann boundary conditions is discussed. By using the cross iteration method and the Schauder's fixed point theorem, we reduce the existence of travelling waves to the existence of a pair of upper-lower solutions. By constructing a pair of upper-lower solutions, we derive the existence of a travelling wave connecting the disease-free steady state and the endemic steady state. Numerical simulations are carried out to illustrate the main results.     

Mathematical analysis of an age-structured population model with space-limited recruitment

In this paper, we investigate structured population model of marine invertebrate whose life stage is composed of sessile adults and pelagic larvae, such as barnacles contained in a local habitat. First we formulate the basic model as an Cauchy problem on a Banach space to discuss the existence and uniqueness of non-negative solution. Next we define the basic reproduction number R0 to formulate the invasion condition under which the larvae can successfully settle down in the completely vacant habitat. Subsequently we examine existence and stability of steady states. We show that the trivial steady state is globally asymptotically stable if R0 < or = 1, whereas it is unstable if R0 > 1. Furthermore, we show that a positive (non-trivial) steady state uniquely exists if R0 > 1 and it is locally asymptotically stable as far as absolute value of R0 - 1 is small enough.     

Time-delayed SIS epidemic model with population awareness

This paper analyses the dynamics of infectious disease with a concurrent spread of disease awareness. The model includes local awareness due to contacts with aware individuals, as well as global awareness due to reported cases of infection and awareness campaigns. We investigate the effects of time delay in response of unaware individuals to available information on the epidemic dynamics by establishing conditions for the Hopf bifurcation of the endemic steady state of the model. Analytical results are supported by numerical bifurcation analysis and simulations.     

Limits to runaway sexual selection: The wallflower paradox

In his mathematical treatment of Fisher's ideas on sexual selection (so-called runaway selection) Lande (1981) predicted that males may evolve increasingly elaborate sexual characters despite opposing viability selection as a consequence of the associated costs. Lande thereby assumed that female mate preferences are not subject to selection since (1) females are all inseminated and (2) the quantity and quality of their offspring are independent of the female's mate preferences. Kirkpatrick (1985) removed the latter assumption and investigated the consequences for the mean phenotype with respect to both female and male traits. He also explored the dynamics of the (co)-variance matrix by numerical methods. In this paper we consider a simpler model with just two multi-allelic loci. This enables us to derive explicit expressions for (co)-variances under steady state conditions. Rather than assume natural selection through differential fertility (as in Kirkpatrick, 1985), we take sexual selection on females into account by modelling the preference-dependent risk that females remain unmated. We argue that this wallflower effect is a realistic feature of any mating system, since it merely depends on the existence of (1) variation in mating preferences and (2) a finite mating season. Our approach provided an insight into the dynamic behaviour of the means of the phenotypes. This is because the dynamics of the means depend on the steady state (co)-variance matrix. Thus, an insight into the former requires explicit expressions for the latter. Whereas Lande and Kirkpatrick predicted runaway processes, despite opposing viability selection, our model predicts a globally stable steady state, i.e. no runaway, even without opposing viability selection (under the assumption of an asymptotically stable steady state of the (co)-variances. Admittedly, we have no analytic proof of this stability but only support for it, based on simulations.) The absence of the runaway processes in our model is caused by the wallflower effect, since it imposes constraints on the steady state of the (co)-variance matrix. When mutational input applies to female traits but not to male traits, explicit expressions for the (co)-variances under steady state conditions can be derived, and these show that: (1) both the genetic covariance and the variance of male traits are equal to zero, but (2) the variance of the female trait exceeds to zero. Should there be mutational input influencing the male trait, then these results would suggest that the male-to-female ratio of variances is much smaller than unity. This prediction is of tremendous importance for speciation through founding events.     

An age-structured epidemic model of rotavirus with vaccination

The recent approval of a rotavirus vaccine in Mexico motivates this study on the potential impact of the use of such a vaccine on rotavirus prevention and control. An age-structured model that describes the rotavirus transmission dynamics of infections is introduced. Conditions that guarantee the local and global stability analysis of the disease-free steady state distribution as well as the existence of an endemic steady state distribution are established. The impact of maternal antibodies on the implementation of vaccine is evaluated. Model results are used to identify optimal age-dependent vaccination strategies. A convergent numerical scheme for the model is introduced but not implemented. This paper is dedicated to Prof. K. P. Hadeler, who continues to push the frontier of knowledge in mathematical biology.     

Stability and Bifurcations in an Epidemic Model with Varying Immunity Period

An epidemic model with distributed time delay is derived to describe the dynamics of infectious diseases with varying immunity. It is shown that solutions are always positive, and the model has at most two steady states: disease-free and endemic. It is proved that the disease-free equilibrium is locally and globally asymptotically stable. When an endemic equilibrium exists, it is possible to analytically prove its local and global stability using Lyapunov functionals. Bifurcation analysis is performed using DDE-BIFTOOL and traceDDE to investigate different dynamical regimes in the model using numerical continuation for different values of system parameters and different integral kernels.