Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission

A precise definition of the basic reproduction number, , is presented for a general compartmental disease transmission model based on a system of ordinary differential equations. It is shown that, if , then the disease free equilibrium is locally asymptotically stable; whereas if , then it is unstable. Thus, is a threshold parameter for the model. An analysis of the local centre manifold yields a simple criterion for the existence and stability of super- and sub-threshold endemic equilibria for near one. This criterion, together with the definition of , is illustrated by treatment, multigroup, staged progression, multistrain and vector–host models and can be applied to more complex models. The results are significant for disease control.     

Spatial patterns in a discrete-time SIS patch model

How do spatial heterogeneity, habitat connectivity, and different movement rates among subpopulations combine to influence the observed spatial patterns of an infectious disease? To find out, we formulated and analyzed a discrete-time SIS patch model. Patch differences in local disease transmission and recovery rates characterize whether patches are low-risk or high-risk, and these differences collectively determine whether the spatial domain, or habitat, is low-risk or high-risk. In low-risk habitats, the disease persists only when the mobility of infected individuals lies below some threshold value, but for high-risk habitats, the disease always persists. When the disease does persist, then there exists an endemic equilibrium (EE) which is unique and positive everywhere. This EE tends to a spatially inhomogeneous disease-free equilibrium (DFE) as the mobility of susceptible individuals tends to zero. The limiting DFE is nonempty on all low-risk patches and it is empty on at least one high-risk patch. Sufficient conditions for the limiting DFE to be empty on other high-risk patches are given in terms of disease transmission and recovery rates, habitat connectivity, and the infected movement rate. These conditions are also illustrated using numerical examples.     

一类具有常数迁入且总入口在变化的SIRI传染病模型的稳定性

讨论一类具有常数迁入率,染病类有病死且有效接触率依赖于总人数的SIRI传染病模型.给出了基本再生数σ的表达式.如果σ≤1,则疾病消除平衡点是全局稳定的;如果σ＞1,则存在唯一的传染病平衡点且是局部渐近稳定的.对具有双线性传染率和标准传染率的相应模型,进一步证明了当σ＞1时传染病平衡点的全局稳定性.     

具有饱和发生率的病毒感染模型的全局稳定性分析

讨论了一类具有饱和发生率的病毒感染数学模型,分析得到了无病平衡点和持续带毒平衡点的全局稳定性条件.当病毒感染的基本再生数R_01时,无病平衡点全局渐近稳定;当R_01时,持续带毒平衡点全局渐近稳定.     

The minimum effort required to eradicate infections in models with backward bifurcation

We study an epidemiological model which assumes that the susceptibility after a primary infection is r times the susceptibility before a primary infection. For r = 0 (r = 1) this is the SIR (SIS) model. For r > 1 + (μ/α) this model shows backward bifurcations, where μ is the death rate and α is the recovery rate. We show for the first time that for such models we can give an expression for the minimum effort required to eradicate the infection if we concentrate on control measures affecting the transmission rate constant β. This eradication effort is explicitly expressed in terms of α,r, and μ As in models without backward bifurcation it can be interpreted as a reproduction number, but not necessarily as the basic reproduction number. We define the relevant reproduction numbers for this purpose. The eradication effort can be estimated from the endemic steady state. The classical basic reproduction number R ₀ is smaller than the eradication effort for r > 1 + (μ/α) and equal to the effort for other values of r. The method we present is relevant to the whole class of compartmental models with backward bifurcation.Dedicated to Karl Peter Hadeler on the occasion of his 70th birthday.     

Qualitative analysis of models with different treatment protocols to prevent antibiotic resistance

This paper is concerned with the qualitative analysis of two models [S. Bonhoeffer, M. Lipsitch, B.R. Levin, Evaluating treatment protocols to prevent antibiotic resistance, Proc. Natl. Acad. Sci. USA 94 (1997) 12106] for different treatment protocols to prevent antibiotic resistance. Detailed qualitative analysis about the local or global stability of the equilibria of both models is carried out in term of the basic reproduction number R₀. For the model with a single antibiotic therapy, we show that if R₀ < 1, then the disease-free equilibrium is globally asymptotically stable; if R₀ > 1, then the disease-endemic equilibrium is globally asymptotically stable. For the model with multiple antibiotic therapies, stabilities of various equilibria are analyzed and combining treatment is shown better than cycling treatment. Numerical simulations are performed to show that the dynamical properties depend intimately upon the parameters.     

The effects of human movement on the persistence of vector-borne diseases

With the recent resurgence of vector-borne diseases due to urbanization and development there is an urgent need to understand the dynamics of vector-borne diseases in rapidly changing urban environments. For example, many empirical studies have produced the disturbing finding that diseases continue to persist in modern city centers with zero or low rates of transmission. We develop spatial models of vector-borne disease dynamics on a network of patches to examine how the movement of humans in heterogeneous environments affects transmission. We show that the movement of humans between patches is sufficient to maintain disease persistence in patches with zero transmission. We construct two classes of models using different approaches: (i) Lagrangian models that mimic human commuting behavior and (ii) Eulerian models that mimic human migration. We determine the basic reproduction number R₀ for both modeling approaches. We show that for both approaches that if the disease-free equilibrium is stable (R₀<1) then it is globally stable and if the disease-free equilibrium is unstable (R₀>1) then there exists a unique positive (endemic) equilibrium that is globally stable among positive solutions. Finally, we prove in general that Lagrangian and Eulerian modeling approaches are not equivalent. The modeling approaches presented provide a framework to explore spatial vector-borne disease dynamics and control in heterogeneous environments. As an example, we consider two patches in which the disease dies out in both patches when there is no movement between them. Numerical simulations demonstrate that the disease becomes endemic in both patches when humans move between the two patches.     

An SEIS epidemic model with transport-related infection

In this paper, an SEIS epidemic model is proposed to study the effect of transport-related infection on the spread and control of infectious disease. New result implies that traveling of the exposed (means exposed but not yet infectious) individuals can bring disease from one region to other regions even if the infectious individuals are inhibited from traveling among regions. It is shown that transportation among regions will change the disease dynamics and break infection out even if infectious diseases will go to extinction in each isolated region without transport-related infection. In addition, our analysis shows that transport-related infection intensifies the disease spread if infectious diseases break out to cause an endemic situation in each region, in the sense of that both the absolute and relative size of patients increase. This suggests that it is very essential to strengthen restrictions of passengers once we know infectious diseases appeared.     

A general multi-strain model with environmental transmission: Invasion conditions for the disease-free and endemic states

Although many infectious diseases of humans and wildlife are transmitted via an environmental reservoir, the theory of environmental transmission remains poorly elaborated. Here we introduce an SIR-type multi-strain disease transmission model with perfect cross immunity where environmental transmission is broadly defined by three axioms. We establish the conditions under which a multi-strain endemic state is invaded by another strain which is both directly and environmentally transmitted. We discuss explicit forms for environmental transmission terms and apply our newly derived invasion conditions to a two-strain system. Then, we consider the case of two strains with matching basic reproduction numbers (i.e., R₀), one directly transmitted only and the other both directly and environmentally transmitted, invading each other's endemic state. We find that the strain which is only directly transmitted can invade the endemic state of the strain with mixed transmission. However, the endemic state of the first strain is neutrally stable to invasion by the second strain. Thus, our results suggest that environmental transmission makes the endemic state less resistant to invasion.     

具有脉冲出生和脉冲接种的SIR传染病模型

考虑了脉冲出生、脉冲接种、垂直传染、因病死亡等因素,建立了脉冲出生和脉冲接种同时进行的SIR传染病模型,通过分析无病周期解的存在性以及稳定性,得出疾病灭绝的条件.     

Age-structured homogeneous epidemic systems with application to the MSEIR epidemic model

In this paper, we develop a new approach to deal with asymptotic behavior of the age-structured homogeneous epidemic systems and discuss its application to the MSEIR epidemic model. For the homogeneous system, there is no attracting nontrivial equilibrium, instead we have to examine existence and stability of persistent solutions. Assuming that the host population dynamics can be described by the stable population model, we rewrite the basic system into the system of ratio age distribution, which is the age profile divided by the stable age profile. If the host population has the stable age profile, the ratio age distribution system is reduced to the normalized system. Then we prove the stability principle that the local stability or instability of steady states of the normalized system implies that of the corresponding persistent solutions of the original homogeneous system. In the latter half of this paper, we prove the threshold and stability results for the normalized system of the age-structured MSEIR epidemic model.      

Dynamic phenomena arising from an extended Core Group model

In order to obtain a reasonably accurate model for the spread of a particular infectious disease through a population, it may be necessary for this model to possess some degree of structural complexity. Many such models have, in recent years, been found to exhibit a phenomenon known as backward bifurcation, which generally implies the existence of two subcritical endemic equilibria. It is often possible to refine these models yet further, and we investigate here the influence such a refinement may have on the dynamic behaviour of a system in the region of the parameter space near R₀=1.We consider a natural extension to a so-called Core Group model for the spread of a sexually transmitted disease, arguing that this may in fact give rise to a more realistic model. From the deterministic viewpoint we study the possible shapes of the resulting bifurcation diagrams and the associated stability patterns. Stochastic versions of both the original and the extended models are also developed so that the probability of extinction and time to extinction may be examined, allowing us to gain further insights into the complex system dynamics near R₀=1. A number of interesting phenomena are observed, for which heuristic explanations are provided.     

具有外来感染者和急慢性阶段的流行病模型的动力学分析

建立和研究了一类具有外来感染者和急慢性阶段的流行病模型,我们假设单位时间内有常数量的外来感染者进入所研究地区,因而得到的模型仅有一个地方病平衡位置.我们证明了当α＜pμ时,地方病平衡位置是全局渐近稳定的.     

具有潜伏和隔离的传染病模型的全局稳定性

研究了一类具有隔离仓室和潜伏仓室的非线性高维自治微分系统SEQIJR传染病模型,得到疾病绝灭与否的阀值一基本再生数R0．证明了当R0≤1时,模型仅存在无病平衡点,且无病平衡点是全局渐近稳定的,疾病最终绝灭;当R0〉1时,模型存在两个平衡点,无病平衡点不稳定,地方病平衡点全局渐近稳定,疾病将持续．隔离措施影响着基本再生数,进而推得结论：适当地增大隔离强度,将有益于有效地控制疾病的蔓延．这就从理论上揭示了隔离对疾病控制的积极作用．     

Modeling the transmission dynamics and control of hepatitis B virus in China

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV) and is a major global health problem. HBV is the most common serious viral infection and a leading cause of death in mainland China. Around 130 million people in China are carriers of HBV, almost a third of the people infected with HBV worldwide and about 10% of the general population in the country; among them 30 million are chronically infected. Every year, 300,000 people die from HBV-related diseases in China, accounting for 40-50% of HBV-related deaths worldwide. Despite an effective vaccination program for newborn babies since the 1990s, which has reduced chronic HBV infection in children, the incidence of hepatitis B is still increasing in China. We propose a mathematical model to understand the transmission dynamics and prevalence of HBV infection in China. Based on the data reported by the Ministry of Health of China, the model provides an approximate estimate of the basic reproduction number R₀=2.406. This indicates that hepatitis B is endemic in China and is approaching its equilibrium with the current immunization program and control measures. Although China made a great progress in increasing coverage among infants with hepatitis B vaccine, it has a long and hard battle to fight in order to significantly reduce the incidence and eventually eradicate the virus.     

The role of health care workers and antiviral drugs in the control of pandemic influenza

Until a vaccine against the new strain becomes available, the response to newly emerged pandemic influenza will consist of the use of antiviral drugs and measures that limit exposure to infectious individuals. These first-line defence measures include isolating cases upon diagnosis, reducing close contacts, the use of personal protective equipment and hygiene, and using antiviral drugs for treatment and prophylaxis. There are significant 'costs' associated with control measures, so to justify such interventions it is important to assess their potential to reduce transmission. In this paper, we determine the effect that a number of different antiviral interventions have on the reproduction number of infectives and the probability that an imported infection fades out, and determine parameter scenarios for which these interventions are able to eliminate an emerging pandemic of influenza. We also assess the role that health care workers play in transmission and the extent to which providing them with antiviral prophylaxis and personal protective equipment modifies this role. Our results indicate that this class requires protection to avoid a greatly disproportionate contribution to early infective numbers, and for the maintenance of a stable health care system. Further, we show that the role children play in increasing transmission is moderate, in spite of closer mixing with other children.     

Backward bifurcation,equilibrium and stability phenomena in a three-stage extended BRSV epidemic model

In this paper we consider the phenomenon of backward bifurcation in epidemic modelling illustrated by an extended model for Bovine Respiratory Syncytial Virus (BRSV) amongst cattle. In its simplest form, backward bifurcation in epidemic models usually implies the existence of two subcritical endemic equilibria for R ₀ < 1, where R ₀ is the basic reproductive number, and a unique supercritical endemic equilibrium for R ₀ > 1. In our three-stage extended model we find that more complex bifurcation diagrams are possible. The paper starts with a review of some of the previous work on backward bifurcation then describes our three-stage model. We give equilibrium and stability results, and also provide some biological motivation for the model being studied. It is shown that backward bifurcation can occur in the three-stage model for small b, where b is the common per capita birth and death rate. We are able to classify the possible bifurcation diagrams. Some realistic numerical examples are discussed at the end of the paper, both for b small and for larger values of b.      

A new SEIR epidemic model with applications to the theory of eradication and control of diseases, and to the calculation of R0

We present a novel SEIR (susceptible-exposure-infective-recovered) model that is suitable for modeling the eradication of diseases by mass vaccination or control of diseases by case isolation combined with contact tracing, incorporating the vaccine efficacy or the control efficacy into the model. Moreover, relying on this novel SEIR model and some probabilistic arguments, we have found four formulas that are suitable for estimating the basic reproductive numbers R(0) in terms of the ratio of the mean infectious period to the mean latent period of a disease. The ranges of R(0) for most known diseases, that are calculated by our formulas, coincide very well with the values of R(0) estimated by the usual method of fitting the models to observed data.     

Estimating the immunity coverage required to prevent epidemics in a community of households

An estimation of the immunity coverage needed to prevent future outbreaks of an infectious disease is considered for a community of households. Data on outbreak size in a sample of households from one epidemic are used to derive maximum likelihood estimates and confidence bounds for parameters of a stochastic model for disease transmission in a community of households. These parameter estimates induce estimates and confidence bounds for the basic reproduction number and the critical immunity coverage, which are the parameters of main interest when aiming at preventing major outbreaks in the future. The case when individuals are homogeneous, apart from the size of their household, is considered in detail. The generalization to the case with variable infectivity, susceptibility and/or mixing behaviour is discussed more briefly. The methods are illustrated with an application to data on influenza in Tecumseh, Michigan.