Treatment strategies for the latent tuberculosis infections.

This study investigates the dynamics of tuberculosis transmission through mathematical modeling, incorporating exogenous reinfections and different treatment approaches for latent tuberculosis infections. We examine three types of treatment rates: saturated, unsaturated, and mass screening-then-treatment. Our results reveal that both saturated treatment and mass screening-then-treatment can lead to a backward bifurcation, while unsaturated treatment does not. To determine the global dynamics of the models, we employ a persistent approach that avoids classifying the steady mode. By applying the models to China, we demonstrate that the data favors the use of unsaturated treatment. If unsaturated treatment is not feasible, the optimal strategy is to screen high-risk groups, identify LTBIs, and administer unsaturated treatment. Saturated treatments are not recommended.

Spatially antiviral dynamics determines HCV in vivo replication and evolution.

In this article, we establish HCV in a host growth partial-differential equation model to analyze the antiviral dynamics. A numerical method to analyze the basic reproductive number of this model is established and we find that for the without drug model, the diffusion rate of the virus and liver length have seldom influence on the growth of the virus. For the with drug model, we find the different pharmic factors have different effect on the virus. Based on this with drug model, we also introduce a semi-stochastic simulation method with which to analyze the virus in host evolution. Our result shows how different drugs can drive the virus in host evolution.

Personalized life expectancy and treatment benefit index of antiretroviral therapy.

BACKGROUND: The progression of Human Immunodeficiency Virus (HIV) within host includes typical stages and the Antiretroviral Therapy (ART) is shown to be effective in slowing down this progression. There are great challenges in describing the entire HIV disease progression and evaluating comprehensive effects of ART on life expectancy for HIV infected individuals on ART. METHODS: We develop a novel summative treatment benefit index (TBI), based on an HIV viral dynamics model and linking the infection and viral production rates to the Weibull function. This index summarizes the integrated effect of ART on the life expectancy (LE) of a patient, and more importantly, can be reconstructed from the individual clinic data. RESULTS: The proposed model, faithfully mimicking the entire HIV disease progression, enables us to predict life expectancy and trace back the timing of infection. We fit the model to the longitudinal data in a cohort study in China to reconstruct the treatment benefit index, and we describe the dependence of individual life expectancy on key ART treatment specifics including the timing of ART initiation, timing of emergence of drug resistant virus variants and ART adherence. CONCLUSIONS: We show that combining model predictions with monitored CD4 counts and viral loads can provide critical information about the disease progression, to assist the design of ART regimen for maximizing the treatment benefits.

Predicting the HIV/AIDS epidemic and measuring the effect of mobility in mainland China.

HIV has spread widely in mainland China, but there is significant geographic variation in the severity of the epidemic. We aimed to assess the HIV/AIDS epidemic in mainland China accurately, and address the effect of population mobility on it. Markov-Chain Monte-Carlo simulations and Latin Hypercube Sampling were used to estimate the basic reproductive ratio and its sensitivity to parameter variations. We estimated a mean reproduction number of 1.708 (95% CI 1.440-1.977). Our analysis using national surveillance data indicates that HIV-positive individuals most likely move from economically developed regions to regions with more numerous HIV cases, while mobility of AIDS patients likely flows in the opposite direction, due to the current policy that AIDS patients must return to their registered residence to receive free antiretroviral therapy. Our results based on a spatially stratified population dynamical model show increasing mobility rates of HIV/AIDS cases can have a significant effect on the number of HIV/AIDS cases per province and has the potential to decrease the overall number of HIV/AIDS cases in the country. We recommend that the community-based HIV/AIDS support and care program should be implemented by some local governments (especially in epidemically severe areas) to mitigate HIV infections in China.

Viral dynamics model with CTL immune response incorporating antiretroviral therapy.

We present two HIV models that include the CTL immune response, antiretroviral therapy and a full logistic growth term for uninfected CD4+ T-cells. The difference between the two models lies in the inclusion or omission of a loss term in the free virus equation. We obtain critical conditions for the existence of one, two or three steady states, and analyze the stability of these steady states. Through numerical simulation we find substantial differences in the reproduction numbers and the behaviour at the infected steady state between the two models, for certain parameter sets. We explore the effect of varying the combination drug efficacy on model behaviour, and the possibility of reconstituting the CTL immune response through antiretroviral therapy. Furthermore, we employ Latin hypercube sampling to investigate the existence of multiple infected equilibria.

A tuberculosis model with seasonality.

The statistical data of tuberculosis (TB) cases show seasonal fluctuations in many countries. A TB model incorporating seasonality is developed and the basic reproduction ratio R(0) is defined. It is shown that the disease-free equilibrium is globally asymptotically stable and the disease eventually disappears if R(0)<1, and there exists at least one positive periodic solution and the disease is uniformly persistent if R(0)>1. Numerical simulations indicate that there may be a unique positive periodic solution which is globally asymptotically stable if R(0)>1. Parameter values of the model are estimated according to demographic and epidemiological data in China. The simulation results are in good accordance with the seasonal variation of the reported cases of active TB in China.

Projection of tuberculosis incidence with increasing immigration trends.

Tuberculosis (TB) incidence rates vary substantially from regions to regions and from countries to countries. In countries such as Canada where TB incidence rate is low, increasing immigration trends may have significant impact on the TB transmission patterns in these countries. In this study we formulate a deterministic epidemiological model of TB transmission in two demographically distinct populations: Canadian born and foreign born populations, in order to investigate the effects of this demographic distinction on the short-term incidence and long-term transmission dynamics, and with special emphasis on the impact of immigration latent TB cases on the overall TB incidence rate in the whole population.

Bifurcation analysis of HIV-1 infection model with cell-to-cell transmission and immune response delay.

A within-host viral infection model with both virus-to-cell and cell-to-cell transmissions and time delay in immune response is investigated. Mathematical analysis shows that delay may destabilize the infected steady state and lead to Hopf bifurcation. Moreover, the direction of the Hopf bifurcation and the stability of the periodic solutions are investigated by normal form and center manifold theory. Numerical simulations are done to explore the rich dynamics, including stability switches, Hopf bifurcations, and chaotic oscillations.

Global stability of a multi-group model with vaccination age, distributed delay and random perturbation.

A multi-group epidemic model with distributed delay and vaccination age has been formulated and studied. Mathematical analysis shows that the global dynamics of the model is determined by the basic reproduction number R0: the disease-free equilibrium is globally asymptotically stable if R0 ≤ 1, and the endemic equilibrium is globally asymptotically stable if R0 > 1. Lyapunov functionals are constructed by the non-negative matrix theory and a novel grouping technique to establish the global stability. The stochastic perturbation of the model is studied and it is proved that the endemic equilibrium of the stochastic model is stochastically asymptotically stable in the large under certain conditions.

A discrete epidemic model for SARS transmission and control in China.

Severe acute respiratory syndrome (SARS) is a rapidly spreading infectious disease which was transmitted in late 2002 and early 2003 to more than 28 countries through the medium of international travel. The evolution and spread of SARS has resulted in an international effort coordinated by the World Health Organization (WHO). We have formulated a discrete mathematical model to investigate the transmission of SARS and determined the basic reproductive number for this model to use as a threshold to determine the asymptotic behavior of the model. The dependence of the basic reproductive number on epidemic parameters has been studied. The parameters of the model have been estimated on the basis of statistical data and numerical simulations have been carried out to describe the transmission process for SARS in China. The simulation results matches the statistical data well and indicate that early quarantine and a high quarantine rate are crucial to the control of SARS.

Bifurcation analysis of a discrete SIS model with bilinear incidence depending on new infection.

A discrete SIS epidemic model with the bilinear incidence depending on the new infection is formulated and studied. The condition for the global stability of the disease free equilibrium is obtained. The existence of the endemic equilibrium and its stability are investigated. More attention is paid to the existence of the saddle-node bifurcation, the flip bifurcation, and the Hopf bifurcation. Sufficient conditions for those bifurcations have been obtained. Numerical simulations are conducted to demonstrate our theoretical results and the complexity of the model.

Global stability of the endemic equilibrium of a discrete SIR epidemic model.

The basic reproductive number R 0 of a discrete SIR epidemic model is defined and the dynamical behavior of the model is studied. It is proved that the disease free equilibrium is globally asymptotically stable if R 0 < 1 , and the persistence of the model is obtained when R 0 > 1 . The main attention is paid to the global stability of the endemic equilibrium. Sufficient conditions for the global stability of the endemic equilibrium are established by using the comparison principle. Numerical simulations are done to show our theoretical results and to demonstrate the complicated dynamics of the model.

Estimates of tuberculosis progression rate of children in China.

In this paper, a discrete mathematical model is formulated to describe tuberculosis (TB) progression from latent infection to active disease. The data of national TB epidemiology surveys in China are taken to estimate the TB progression rate for children aged 0-14 years. The progression rate obtained in this paper gives a detailed and better estimate of TB progression rate among children.

Modelling disease spread in dispersal networks at two levels.

A network model at both the population and individual levels, which simulates both between-patch and within-patch dynamics, is proposed. We investigated the effects of dispersal networks and distribution of local dynamics on the outcome of an epidemic at the population level. Numerical studies show that disease control on random networks may be easier than on small-world networks, depending on the initial distribution of the local dynamics. Spatially separating instead of gathering patches where disease locally persists is beneficial to global disease control if dispersal networks are a type of small-world networks. Dispersal networks with higher degree lead to a higher mean value of R0. Furthermore, irregularity of network and randomization are beneficial to disease stabilization and greatly affect the resulting global dynamics.

Community-based measures for mitigating the 2009 H1N1 pandemic in China.

Since the emergence of influenza A/H1N1 pandemic virus in March-April 2009, very stringent interventions including Fengxiao were implemented to prevent importation of infected cases and decelerate the disease spread in mainland China. The extent to which these measures have been effective remains elusive. We sought to investigate the effectiveness of Fengxiao that may inform policy decisions on improving community-based interventions for management of on-going outbreaks in China, in particular during the Spring Festival in mid-February 2010 when nationwide traveling will be substantially increased. We obtained data on initial laboratory-confirmed cases of H1N1 in the province of Shaanxi and used Markov-chain Monte-Carlo (MCMC) simulations to estimate the reproduction number. Given the estimates for the exposed and infectious periods of the novel H1N1 virus, we estimated a mean reproduction number of 1.68 (95% CI 1.45-1.92) and other A/H1N1 epidemiological parameters. Our results based on a spatially stratified population dynamical model show that the early implementation of Fengxiao can delay the epidemic peak significantly and prevent the disease spread to the general population but may also, if not implemented appropriately, cause more severe outbreak within universities/colleges, while late implementation of Fengxiao can achieve nothing more than no implementation. Strengthening local control strategies (quarantine and hygiene precaution) is much more effective in mitigating outbreaks and inhibiting the successive waves than implementing Fengxiao. Either strong mobility or high transport-related transmission rate during the Spring Festival holiday will not reverse the ongoing outbreak, but both will result in a large new wave. The findings suggest that Fengxiao and travel precautions should not be relaxed unless strict measures of quarantine, isolation, and hygiene precaution practices are put in place. Integration and prompt implementation of these interventions can significantly reduce the overall attack rate of pandemic outbreaks.

Global stability of a class of discrete age-structured SIS models with immigration.

Immigration has an important influence on the growth of population and the transmission dynamics of infectious diseases. A discrete age-structured epidemic SIS model with immigration is formulated and its dynamical behavior is studied in this paper. It is found that population growth will be determined by the reproductive number and the immigration rate. In the simple case without infected immigration, the basic reproductive number is defined, and the global stability of equilibria is investigated. In the case with infected immigration, there is no disease-free equilibrium, and there always exists an endemic equilibrium, and the global stability conditions of the unique endemic equilibrium is obtained.

Oscillatory viral dynamics in a delayed HIV pathogenesis model.

We consider an HIV pathogenesis model incorporating antiretroviral therapy and HIV replication time. We investigate the existence and stability of equilibria, as well as Hopf bifurcations to sustained oscillations when drug efficacy is less than 100%. We derive sufficient conditions for the global asymptotic stability of the uninfected steady state. We show that time delay has no effect on the local asymptotic stability of the uninfected steady state, but can destabilize the infected steady state, leading to a Hopf bifurcation to periodic solutions in the realistic parameter ranges.