结核病时空传播模型与危险因素评估
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摘要
流动人群、耐药肺结核和TB/HIV双重感染是当前全球结核病防控工作面临的三大挑战,尤其流动人群肺结核是耐药肺结核和TB/HIV双重感染的重要来源。本文以大量流行病学现场调查资料为基础,结合地理信息系统(GIS)的空间分析技术,从经济、病人延误、流动人群等几个方面系统分析了我国肺结核流行情况,同时对流动人群中经常发生的诊断延误、治疗延误等问题进行了初步探讨,并建立了相应的理论传播模型,最后根据结核病延误率、发现率、耐药率和治愈率对全国结核病疫情趋势进行了预测。
本文通过空间模型的定量分析,首次在全国范围内以县为单位研究了涂阳肺结核的空间分布模式,确定了中部和西北2个涂阳肺结核热点区域。进一步研究发现,流动人群是导致结核病在全球范围内广泛传播的主要原因之一,是大量耐药肺结核病人的重要来源,是我国乃至全球结核病居高难下的罪魁祸首。本文进而以北京地区结核病时空分布特征为基础,首次提出了北京结核病的分布模式,确定了北京18区和220个乡镇结核病热点区域。
本文在动力学理论分析的基础上,首次将流动人群作为一个独立的群体引入结核病传播模型,建立了流动人群结核病动力学传播模型,利用Liypunov和Lasalle不变集原理证明了无病平衡点的全局稳定性,利用Michal Li几何方法,证明8维微分方程正平衡点的全局稳定性。为验证模型的正确性,本文还结合两类具体数据模拟了两类流动人群结核病发病情况,即加拿大和北京地区本地人群和流动人群的结核病发病情况,模拟结果显示,只要流动人群中存在病人,当地的结核病疫情就不会消失。
本文还建立了结核病诊断和治疗延误模型,并利用Liypunov和Lasalle不变集原理证明了模型无病点的全局稳定性。数值模拟结果显示,模型正平衡点全局稳定,且病人延误对发病率的影响远远大于医生延误的影响。
通过全国4次抽样调查患病率和肺结核年报告率的对比分析发现,我国至少2/3的涂阳肺结核病人没有得到发现。本文最后利用全国4次抽样调查资料,使用发现率、延误率、耐药率和治愈率4个可调指标预测了2010年全国结核病疫情。全文共7章分4部分。第一部分由第3章组成,讨论了全国涂阳肺结核的分布和影响因素,论述了贫穷与结核病的关系,确定政府扶贫策略(包括DOTS策略)和流动人群分别是2003-2005年贫困地区和经济发达地区报告率偏高的原因;第2部分由第4、5章组成,讨论了流动人群的时空传播模型。首先对北京地区流动人群结核病疫情进行了探索性的多水平空间分析,分析结果发现,北京流动人群结核病具有明显的空间聚集性,流动人群对北京结核病发病率和18区发病率的差异存在显著性影响。随后建立了流动人群结核病传播数学模型,探讨结核病长期动力学传播行为,理论分析证实,要从人群中彻底消除结核病,必须解决流动人群的结核病问题;论文第3部分由第6章组成,讨论了病人珍断和治疗延误对结核病发病的影响,显然延误与结核病发病率正相关;第7章构成了文章的第4部分,利用全国4次结核病抽样调查数据对全国结核病疫情进行预测。
本文不仅从理论上完成了8维微分方程组的稳定性分析,获得动力学模型稳定性的阈值条件,促进了理论方法学与结核病流行病学的交叉渗透,同时其研究结果为结核病防控工作者制定有针对性的防控策略提供了科学依据,具有重要的现实意义,也为其他传染病的研究提供了新的研究思路和线索。利用动力学模型和时空模型对某一具体疾病进行定量研究和探讨在我国尚没有公开发表的研究成果和报道,本研究填补了我国结核病理论流行病学和相应领域的研究空白。
Migrant population, Drug-resistant tuberculosis and TB/HIV co-infection are three main challenges for tuberculosis control in worldwide. Especially, migrants are responsible for the huge number of drug-resistant tuberculosis and HIV/ADIS co-infecition. Based on huge field epidemiology data, the paper conducted a retrospective analysis to tuberculosis among the migrants in Beijing, and further investigated the influence of delay of diagnosis and theraphy on tuberculosis by spatial model, dynamical mathematical model and temporal spatial model. Furthermore, the paper predicted the trend of tuberculosis in China based on finding rate, delay rate, cure rate and drug-resistant rate.
To our knowledge, such research was first time to confirm the distribution pattern of sputum positive tuberculosis and two hotspots areas in countrywide, the impact of migrant population on the tuberculosis in Beijing and the distribution pattern of tuberculosis and hotspots. In the dynamic model research, the migrant population was first incorporated into mathematical model as a separate unit and the big chanllege was the proof of stability of endemic equailibrium. The paper also detects the influence of delay rate, finding rate, drug-resistant rate and cure rate on the epidemiology of tuberculosis and predicts the number of tuberculosis cases in 2010 in nationwide. The analytical results indicated that migrant population was responsible for transmission of tuberculosis in worldwide and resulted in the huge number of drug-resistant tuberculosis cases.
Our work①finished the theoretical analysis for the 8 dimension equation and got the threshold for the dying out of tuberculosis within population, which will push the crossing of the theoretical methods and tuberculosis .②will support to establish the effective tuberculosis control measures.③provided new thought and method to other infectious disease.
The thesis includes seven chapters. The first chapter presents the current status of tuberculosis all over the world and the background of the temporal-spatial model which have been conducted to the tuberculosis study. The second chapter shows the data sources which have been used to investigate the transmission and distribution of tuberculosis. The third chapter detects the factors which effect tuberculosis and finds that migrant population plays an important role in the spread of tuberculosis as well as poverty. The fourth and fifth chapters begin to investigate the contribution of migrants to epidemic of tuberculosis. The spatial statistical analysis results indicate that the disease cluster at 18 district level among the migrant population. Migrants not only are associated with the epidemic of tuberculosis in Beijing, but also contribute to the differentia of tuberculosis between 18 districts. The theoretical analysis reveals that the long term behavior of tuberculosis is global asymptotic stability. The disease can be eradicated from population if the basic reproductive number of permanent residents and immigrants less than one, respectively. Otherwise, the disease persists in an endemic equilibrium. In the chapter six, we confirm the delay of diagnosis and treatment is positive associated with prevalence of tuberculosis as well as the resistant-drug do. However, we establish a model to predict the epidemic trend of tuberculosis of China and further estimate the case in 2010 in the final chapter.
To our knowledge, to investigate a special disease using spatial-temporal model have not been reported in China. Our works fill the gaps of theoretical epidemiology of tuberculosis field in our country.
本文通过空间模型的定量分析,首次在全国范围内以县为单位研究了涂阳肺结核的空间分布模式,确定了中部和西北2个涂阳肺结核热点区域。进一步研究发现,流动人群是导致结核病在全球范围内广泛传播的主要原因之一,是大量耐药肺结核病人的重要来源,是我国乃至全球结核病居高难下的罪魁祸首。本文进而以北京地区结核病时空分布特征为基础,首次提出了北京结核病的分布模式,确定了北京18区和220个乡镇结核病热点区域。
本文在动力学理论分析的基础上,首次将流动人群作为一个独立的群体引入结核病传播模型,建立了流动人群结核病动力学传播模型,利用Liypunov和Lasalle不变集原理证明了无病平衡点的全局稳定性,利用Michal Li几何方法,证明8维微分方程正平衡点的全局稳定性。为验证模型的正确性,本文还结合两类具体数据模拟了两类流动人群结核病发病情况,即加拿大和北京地区本地人群和流动人群的结核病发病情况,模拟结果显示,只要流动人群中存在病人,当地的结核病疫情就不会消失。
本文还建立了结核病诊断和治疗延误模型,并利用Liypunov和Lasalle不变集原理证明了模型无病点的全局稳定性。数值模拟结果显示,模型正平衡点全局稳定,且病人延误对发病率的影响远远大于医生延误的影响。
通过全国4次抽样调查患病率和肺结核年报告率的对比分析发现,我国至少2/3的涂阳肺结核病人没有得到发现。本文最后利用全国4次抽样调查资料,使用发现率、延误率、耐药率和治愈率4个可调指标预测了2010年全国结核病疫情。全文共7章分4部分。第一部分由第3章组成,讨论了全国涂阳肺结核的分布和影响因素,论述了贫穷与结核病的关系,确定政府扶贫策略(包括DOTS策略)和流动人群分别是2003-2005年贫困地区和经济发达地区报告率偏高的原因;第2部分由第4、5章组成,讨论了流动人群的时空传播模型。首先对北京地区流动人群结核病疫情进行了探索性的多水平空间分析,分析结果发现,北京流动人群结核病具有明显的空间聚集性,流动人群对北京结核病发病率和18区发病率的差异存在显著性影响。随后建立了流动人群结核病传播数学模型,探讨结核病长期动力学传播行为,理论分析证实,要从人群中彻底消除结核病,必须解决流动人群的结核病问题;论文第3部分由第6章组成,讨论了病人珍断和治疗延误对结核病发病的影响,显然延误与结核病发病率正相关;第7章构成了文章的第4部分,利用全国4次结核病抽样调查数据对全国结核病疫情进行预测。
本文不仅从理论上完成了8维微分方程组的稳定性分析,获得动力学模型稳定性的阈值条件,促进了理论方法学与结核病流行病学的交叉渗透,同时其研究结果为结核病防控工作者制定有针对性的防控策略提供了科学依据,具有重要的现实意义,也为其他传染病的研究提供了新的研究思路和线索。利用动力学模型和时空模型对某一具体疾病进行定量研究和探讨在我国尚没有公开发表的研究成果和报道,本研究填补了我国结核病理论流行病学和相应领域的研究空白。
Migrant population, Drug-resistant tuberculosis and TB/HIV co-infection are three main challenges for tuberculosis control in worldwide. Especially, migrants are responsible for the huge number of drug-resistant tuberculosis and HIV/ADIS co-infecition. Based on huge field epidemiology data, the paper conducted a retrospective analysis to tuberculosis among the migrants in Beijing, and further investigated the influence of delay of diagnosis and theraphy on tuberculosis by spatial model, dynamical mathematical model and temporal spatial model. Furthermore, the paper predicted the trend of tuberculosis in China based on finding rate, delay rate, cure rate and drug-resistant rate.
To our knowledge, such research was first time to confirm the distribution pattern of sputum positive tuberculosis and two hotspots areas in countrywide, the impact of migrant population on the tuberculosis in Beijing and the distribution pattern of tuberculosis and hotspots. In the dynamic model research, the migrant population was first incorporated into mathematical model as a separate unit and the big chanllege was the proof of stability of endemic equailibrium. The paper also detects the influence of delay rate, finding rate, drug-resistant rate and cure rate on the epidemiology of tuberculosis and predicts the number of tuberculosis cases in 2010 in nationwide. The analytical results indicated that migrant population was responsible for transmission of tuberculosis in worldwide and resulted in the huge number of drug-resistant tuberculosis cases.
Our work①finished the theoretical analysis for the 8 dimension equation and got the threshold for the dying out of tuberculosis within population, which will push the crossing of the theoretical methods and tuberculosis .②will support to establish the effective tuberculosis control measures.③provided new thought and method to other infectious disease.
The thesis includes seven chapters. The first chapter presents the current status of tuberculosis all over the world and the background of the temporal-spatial model which have been conducted to the tuberculosis study. The second chapter shows the data sources which have been used to investigate the transmission and distribution of tuberculosis. The third chapter detects the factors which effect tuberculosis and finds that migrant population plays an important role in the spread of tuberculosis as well as poverty. The fourth and fifth chapters begin to investigate the contribution of migrants to epidemic of tuberculosis. The spatial statistical analysis results indicate that the disease cluster at 18 district level among the migrant population. Migrants not only are associated with the epidemic of tuberculosis in Beijing, but also contribute to the differentia of tuberculosis between 18 districts. The theoretical analysis reveals that the long term behavior of tuberculosis is global asymptotic stability. The disease can be eradicated from population if the basic reproductive number of permanent residents and immigrants less than one, respectively. Otherwise, the disease persists in an endemic equilibrium. In the chapter six, we confirm the delay of diagnosis and treatment is positive associated with prevalence of tuberculosis as well as the resistant-drug do. However, we establish a model to predict the epidemic trend of tuberculosis of China and further estimate the case in 2010 in the final chapter.
To our knowledge, to investigate a special disease using spatial-temporal model have not been reported in China. Our works fill the gaps of theoretical epidemiology of tuberculosis field in our country.
引文
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