Modelling and controlling infectious diseases / Se servir de la modélisation pour lutter contre les maladies infectieuses

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    Time lag insensitive approach for estimating HIV-1 transmission direction
    (Wolters Kluwer Health, 2012) Jing Yang; Meng Ge; Xian-Ming Pan
    OBJECTIVES: Identifying the direction of transmission in transmission pairs is important both for forensic investigations and for the monitoring of HIV epidemics, however, reliable methods are not yet available due to the long time lag between infection and sampling in most real cases. DESIGNS: Based on bottleneck effect and coreceptor switching, we aimed at identifying an estimator from sequences of viral gp120 proteins to determine transmission direction between transmission pairs. The estimator should be changed with HIV transmission but was independent of disease progression in an individual. METHODS: Here, we present a novel and reliable approach for identifying transmission direction. We derived a set of conserved patterns, called common patterns, from the sequences of viruses, which differed in their coreceptor usage. The number of unique common patterns in viral sequences decreased with transmission but remained almost constant with the progress of disease in an individual. We used this number as an estimator to determine transmission direction in 73 transmission pairs for which the transmission direction was already known. RESULTS: Our method predicted transmission direction with an accuracy of up to 94.5%. Of greater importance, our approach was not influenced by time lags between infection and sampling, and even transmission direction for transmission pairs with long time lags ranging from 2 years to more than 18 years were correctly determined. CONCLUSION: Our approach for accurately determining transmission direction between transmission pairs is irrespective of the time lag between infection and sampling, which means a promising applications prospect.
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    Mathematical model of humoral immune response to hepatitis B vaccines [Chinese language]
    (2011) Luo Li-li; Meng Gai-li; Ji Zhen-hao; Zhou Yi-cang
    The hepatitis B vaccination is an effective measure to prevent and control the infection of hepatitis B virus(HBV).The persistence of anti-HBs after anti-HBV vaccination and the maintenance of long-term immune memory has been the focus of attention.0n the basis of the hypothesis that long-lived plasma cells maintain the long-term immune response, a mathematical model of humoral immune response i8 formulated to describe the long-term variation of vaccine recipients’anti-HBs.After parameter values ale selected the model simulation is done to show the immune response of the recombinant and plasma-derived vaccines.The long-term immune response is also investigated based on the interaction of the persistence of antigen and long-lived plasma cells.The simulation results show that the model fits the post-vaccination antibody response data well.Finally,the impact of several parameters on the immune effect is discussed. The model and its simulation results may help people to understand the immune response.
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    Discrete age-structured SEIT model with application to tuberculosis transmission in China
    (Elsevier, 2012) Hui Cao; Yicang Zhou
    Age plays an important role in the transmission of some infectious diseases. A discrete SEIT model with age-structure is formulated and studied. The basic reproduction number, R0R0, of the model is defined. It is proved that R0=1R0=1 is a threshold to determine the disease extinction or persistence. The disease-free equilibrium is globally stable (unstable) if R0<1R0<1 (if R0>1R0>1). There exists an endemic equilibrium, and the system is uniformly persistent if R0>1R0>1. The numerical simulation demonstrates that the endemic equilibrium may be globally asymptotically stable. The model is applied to describe tuberculosis (TB) transmission in China. The total number of the population, the incidence rate, the prevalent rate and its age structure match the statistical data well.
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    Estimates of tuberculosis progression rate of children in China
    (Taylor & Francis, 2012) Hui Cao; Yicang Zhou; Fred Brauer
    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.
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    Complex dynamics of discrete SEIS models with simple demography
    (Hindawi Publishing Corporation, 2011) Hui Cao; Yicang Zhou; Baojun Song
    The bifurcation approach has been extensively utilized in theoretical epidemiology. The SEIS model takes into consideration the exposed or latent period of a disease; in the SEIS model an infection does not leave any immunity, thus individuals that have recovered return to being susceptible again. In this study bifurcations and dynamical behaviors of discrete SEIS models with exogenous reinfections are investigated along with some treatment strategies; results suggest treating a fixed percentage of exposed individuals.
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    Threshold dynamics for compartmental epidemic models with impulses
    (Elsevier, 2012) Youping Yang; Yanni Xiao
    The basic reproductive number and its calculation for general impulsive compartmental epidemic models, with pulses on both the infected and the uninfected compartments, are established. Theoretical results show that the basic reproductive number serves as a threshold parameter: the disease dies out if the basic reproductive number is smaller than unity, and breaks out if it is larger than unity. The global dynamics of a viral dynamical model with impulsive immune response is analyzed to study how the vaccination strength and the vaccination interval affect the basic reproductive number and virus progression.
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    Mathematical model of effects of environmental contamination and presence of volunteers on hospital infections in China
    (Elsevier, 2012) Xia Wang; Yanni Xiao; Junrui Wang; Xinxin Lu
    Deterministic and stochastic mathematical models were formulated to investigate the roles that environmental contamination and the presence of volunteers played in the dynamics of hospital infections in China. Semi-stochastic simulation was used to estimate some of the parameters by fitting the observed data and investigating the impacts of interventions such as cleaning, hand hygiene and isolation of admitted MRSA (Methicillin-resistant Staphylococcus aureus) patients on mean prevalence of infection. The basic reproduction number was estimated to be 0.9753. Numerical simulations show that environmental contamination is a threat to hospital infection and free-living bacteria in the environment can promote transmission and initiate infection even if an infection has died out among HCWs (health-care workers) and patients. Sensitivity analysis indicates that a contaminated environment and volunteers contribute substantially to MRSA transmission in hospital infections, and hence effective control measures should be targeted. Hand hygiene of volunteers and cleaning are more effective in reducing the mean prevalence of colonized patients than isolation of newly admitted MRSA-positive patients and hand hygiene of HCWs. Hence volunteers, a cadre of semi-professional nurses, are beneficial to both disease control and supplementary treatment of HCWs if they are well trained. However, isolation of newly admitted MRSA-positive patients could be influential and dominant in reducing the prevalence of infection when the environment within a ward is sufficiently clean.
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    Modeling strategies for controlling H1N1 outbreaks in China
    (World Scientific Publishing Company, 2012) Jin Zhang; Yanni Xiao
    There has been a global attack of A/H1N1 virus in 2009, which widely affected the world’s normal stability and economic development. Since the emergence of the first diagnosed A/H1N1 influenza infected person in 11 May 2009 in China, very strict policy including quarantine and isolation measures were widely implemented to control the spread of this disease before the vaccine appeared. We propose a compartmental model that mimics the infection process of A/H1N1 under control strategies taken in mainland China. Apart from theoretical analysis, using the statistic data of Shaanxi Province, we estimated the unknown epidemiological parameters of this disease in Shaanxi via least-squares fitting method. The estimated control reproductive number of H1N1 for its first peak was Rc1 = 2.555 (95% CI: 2.362–2.748) and that for the second peak was Rc2 = 1.886 (95% CI: 1.765–2.001). Our findings in this paper suggest that neither quarantine nor isolation measures could be relaxed, and the implementation of these interventions can reduce the pandemic outbreak of A/H1N1 pandemic significantly.
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    Modeling primary and secondary drug resistances under China’s “Four-Free-One-Care Policy”
    (World Scientific Publishing Company, 2012) Jie Lou; Lingchen Bu; Esther Han; Yuhua Ruan; Hui Xing; Yiming Shao
    We propose a mathematical model to evaluate the effect of China’s “Four-Free-One-Care Policy” in MSM population in Beijing. We divided the drug resistant HIV patients into two sub-populations: primary drug resistance and secondary drug resistance. Uncertainty and sensitivity analysis based on Latin Hypercube Sampling (LHS) were used for these thresholds of our model. We find that drug-resistant HIV will spread fast in MSM population under China’s current treatment policy. Especially, primary-resistant strain is very likely to dominate the HIV positive MSM individuals after 10 years. The conclusions hint that, China’s outlook on HIV infections is not optimistic if sufficient kinds free second-line drugs in China cannot be put into use in the near future.
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    Threshold virus dynamics with impulsive antiretroviral drug effects
    (Springer, 2011) Jie Lou; Yijun Lou; Jianhong Wu
    The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible.
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    Optimal control of drug therapy : melding pharmacokinetics with viral dynamics
    (Elsevier, 2011-03) Youping Yang; Yanni Xiao; Ning Wang; Jianhong Wu
    Pharmacokinetics were melded with a viral dynamical model to design an optimal drug administration regimen such that the basic reproductive number for the virus was minimized. One-compartmental models with two kinds of drug delivery routes, intravenous and extravascular with multiple dosages, and two drug elimination rates, first order and Michaelis–Menten rates, were considered. We defined explicitly the basic reproductive number for the viral dynamical model melded with pharmacokinetics. When the average plasma drug concentration was constant, intravenous administration of the drug with small dosages applied frequently minimized the basic reproductive number. For extravascular administration, the basic reproductive number initially decreases to a trough point and then increases as the drug dosage increases. When a therapeutic window is considered, numerical studies indicate that the wider the window, the smaller the basic reproductive number. Once the width of the therapeutic window is fixed, the basic reproductive number monotonously declines as the minimum therapeutic level increases. The findings suggest that the existence of drug dosage and drug administration interval that minimize the basic reproductive number could help design the optimal drug administration regimen.
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    Richards model revisited : validation by and application to infection dynamics
    (Elsevier, 2012) Xiang-Sheng Wang; Jianhong Wu; Yong Yang
    Ever since Richards proposed his flexible growth function more than half a century ago, it has been a mystery that this empirical function has made many incredible coincidences with real ecological or epidemic data even though one of its parameters (i.e., the exponential term) does not seem to have clear biological meaning. It is therefore a natural challenge to mathematical biologists to provide an explanation of the interesting coincidences and a biological interpretation of the parameter. Here we start from a simple epidemic SIR model to revisit Richards model via an intrinsic relation between both models. Especially, we prove that the exponential term in the Richards model has a one-to-one nonlinear correspondence to the basic reproduction number of the SIR model. This one-to-one relation provides us an explicit formula in calculating the basic reproduction number. Another biological significance of our study is the observation that the peak time is approximately just a serial interval after the turning point. Moreover, we provide an explicit relation between final outbreak size, basic reproduction number and the peak epidemic size which means that we can predict the final outbreak size shortly after the peak time. Finally, we introduce a constraint in Richards model to address over fitting problem observed in the existing studies and then apply our method with constraint to conduct some validation analysis using the data of recent outbreaks of prototype infectious diseases such as Canada 2009 H1N1 outbreak, GTA 2003 SARS outbreak, Singapore 2005 dengue outbreak, and Taiwan 2003 SARS outbreak. Our new formula gives much more stable and precise estimate of model parameters and key epidemic characteristics such as the final outbreak size, the basic reproduction number, and the turning point, compared with earlier simulations without constraints.
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    Projective clustering using neural networks with adaptive delay and signal transmission loss
    (Massachusetts Institute of Technology, 2011) Jianhong Wu; Zivari-Piran, Hossein; Hunter, John D.; Milton, John G.
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    New pattern-based method for identifying recent HIV-1 infections from the viral env sequence
    (Springerlink, 2012) Jing Yang; XiaYu Xia; Xiang He; SenLin Yang; YuHua Ruan
    The study investigates a pattern-based method for measuring intra-patient viral genetic diversity for determination of recent infections and estimation of population incidence. Pattern-based diversities of recent infections are significantly lower than that of chronic ones. With larger window periods varying from 200 to 350 days, a higher accuracy (90%95%) not affected by advanced disease nor antiretroviral therapy (ART) treatment could be obtained. The pattern-based genetic method is supplementary to existing serology-based assays, both suitable for use in low and high epidemic regions respectively. The envelope (env) gene of HIV/SIV is the most variable of viral genes.
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    Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003–11) : a national observational cohort study
    (Elsevier, 2012-12) Zhongwei Jia; Yuhua Ruan; Qianqian Li; Peiyan Xie; Ping Li
    The World Health Organization (WHO) has recommended that antiretroviral therapy be offered to all HIV-infected individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. Whether a public health approach is feasible, and the outcomes are sustainable at a large scale and in a developing country setting, is assessed in this study. Results show that antiretroviral therapy in serodiscordant couples reduced HIV transmission across China, which suggests that the treatment-as-prevention approach is a feasible public health prevention strategy on a national scale. The durability and generalizability of such protection, however, needs to be further studied.
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    Impact of migrant workers on the tuberculosis transmission : general models and a case study for China
    (American Institute of Mathematical Sciences, 2012-10) Luju Liu; Jianhong Wu; Xiao-Qiang Zhao
    With heavy influx of migrant workers into cities, curbing the spread of large-scale tuberculosis (TB) and HIV infection is an immense challenge. A case study, based on the TB epidemiological and other statistical data in China, indicates that the disease spread can be controlled if effective measures are taken to reduce the reactivation rate of exposed/latent migrant workers. Impact of the migration rate and direction, as well as the duration of home visit stay, on the control of disease spread is also examined numerically. The research develops a mathematical model that factors in epidemiological, social and economic features of migrant workers.
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    Desktop software for patch-clamp raw binary data conversion and preprocessing
    (Hindawi Publishing Corporation, 2011) Ning Zhang; Yutao Tian; Lei Zhang; Zhuo Yang; Tao Zhang; Jishou Ruan
    Via a graphical user interface, raw binary data files can be converted into several kinds of ASCII text files for further analysis, with several pre-processing options. The parameters can also be viewed, modified and exported into ASCII files by a user-friendly Explorer style window. In this study, the desktop software, called PCDReader along with a novel class module, called clsPulseData, directly reads raw data along with the parameters recorded from HEKA instruments without any other program support. The real-time data loading technique and optimized memory management programming makes PCDReader a fast and efficient tool.
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    Processing and analysis of ChIP-seq data [Chinese language]
    (2012) Gao Shan; Zhang Ning; Li Bo; Xu Shuo; Ye Yan-Bo; Ruan Ji-Shou
    The next-generation sequencing coupled with chromatin immunoprecipitation (ChIP-seq) is becoming a key technology for the study of transcriptional regulation in the context of functional genomics. Due to the overwhelming amount of data generated from ChIP-seq experiments, the ChIP-seq data processing brings many new challenges in the field of bioinformatics. Considering the development of data processing skills largely behind that of the ChIP-seq experiment techniques, it is urgent to give a review on the ChIP-seq data processing for more and more oncoming researchers to build or improve algorithms. This paper provides a brief overview of the ChIP-seq data processing, highlighting the main prob-lems and methods in detail, to allow scientists to understand rapidly and deeply.
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    Molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis
    (PLOS, 2012) Wei Cui; Kui Wang; Jishou Ruan; Zhi Qi; Yi Feng; Yiming Shao; Tuszynski, Jack A.
    Research addresses the question of how to uncover the molecular mechanism of a drug, which improves therapeutic efficacy: Oseltamivir/Zanamivir may congruously improve the therapeutic efficacies of CR6261, F10, CR8020 and FI6 by providing an additional affinity to compensate for the loss of affinity between HA and mAb resulting from mutations. However, Oseltamivir or Zanamivir are not expected to generally widen the spectrum of these mAbs. In order to enhance CR6261, CR8020, or for F10 to become universal, we may select Azichromycin, Oseltamivir, or the combination of Azichromycin and Oseltamivir, respectively.
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    Computable features required to evaluate the efficacy of drugs and a universal algorithm to find optimally effective drug in a drug complex
    (PLOS, 2012) Kui Wang; Wei Cui; Gang Hu; Jianzhao Gao; Zhonghua Wu
    Background The H1N1 pandemic in 2009 and the H5N1 pandemic in 2005 demonstrated that the drugs approved to treat influenza A viruses have low efficacy. This provided a stimulus for new studies of influenza A viruses in the context of the methods used in drug design developed over the past 100 years. Finding new universal drugs is the ultimate goal but its long time horizon is incompatible with emergency situations created by reoccurring influenza outbreaks. Therefore, we propose a computer-aided method for finding efficacious drugs and drug complexes based on the use of the DrugBank database. Methods (1) We start by assembling a panel of target proteins. (2) We then assemble a panel of drugs. (3) This is followed by a selection of benchmark binding pockets based on the panel of target proteins and the panel of drugs. (4) We generate a set of computational features, which measure the efficacy of a drug. (5) We propose a universal program to search for drugs and drug complexes. (6) A case study we report here illustrates how to use this universal program for finding an optimal drug and a drug complex for a given target. (7) Validation of the Azirchromycin and Aspirin complex is provided mathematically. (8) Finally, we propose a simple strategy to validate our computational prediction that the Azirchromycin and Aspirin complex should prove clinically effective. Result A set of computable features are mined and then based on these features, a universal program for finding the potential drug &drug complexes is proposed. Using this universal program, the Azirchromycin and Aspirin complex is selected and its efficacy is predicted mathematically. For clinical validation of this finding, future work is still required.