Epidemiology and transmission dynamics of MDR/XDR tuberculosis

描述（由申请人提供）：目前的估计表明，世界上约三分之一的人口感染了M。每年有870万人患上结核病，每年有近200万人死于结核病。结核病控制方案受到多药耐药（MDR）和广泛耐药（XDR）结核病的出现和传播的威胁，因为这些病例的治疗比药物敏感菌株的治疗更复杂、更昂贵且常常不太成功。该计划项目的目标是开展一系列相关的跨学科研究项目，重点关注多药耐药结核病和广泛耐药结核病的出现和传播，并通过开发管理和领导核心、数据库管理和中央M.结核病隔离档案。相关研究项目包括：一项在秘鲁利马进行的与药物敏感和耐药结核病的出现和传播相关的宿主和微生物因素的队列研究;结核菌株多样性及其对MDR出现和传播的贡献;以及一项使用流行病和个体预测模型支持MDR和XDR结核病公共卫生政策和临床决策的研究。 项目1：药物敏感和耐药结核病的宿主和微生物风险因素 描述（申请人提供）：M.结核病是一种非常成功的病原体，每年感染超过800万人并导致超过200万人死亡。据信，世界上三分之一的人口感染了这种微生物，但只有少数感染者会继续发展为活动性疾病。虽然已经描述了疾病进展的一些风险因素，但导致易感性增加的宿主和微生物机制知之甚少。确定与药物敏感和耐药结核病的传播和进展相关的因素可能为重点临床和公共卫生干预提供目标。这种干预措施对于控制耐药结核病特别重要，因为目前的控制措施侧重于有效治疗传染病。长期目标是阐明涉及多药耐药（MDR）和广泛耐药（XDR）结核病的出现和传播的因素，并制定和实施针对这些因素的干预措施，以减少结核病的进展和传播。该项目的具体目标是确定宿主、微生物和环境风险因素，以发展药物敏感（DS）和MDR结核病，并根据其流行病学和临床行为对菌株进行存档，以便将其用于菌株多样性及其对MDR的贡献的基础研究。我们还将建立一个全面的数据库，以便进行实时监测，并用于流行病建模和个人预测模型，这将有助于制定有关耐药结核病治疗的决策。

DESCRIPTION (provided by applicant): Current estimates indicate that about a third of the world's population is infected with M. tuberculosis, 8.7 million individuals develop the disease annually, and almost 2 million die each year from the disease. Tuberculosis control programs are threatened by the emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis since the treatment of these cases is more complex, more costly, and frequently less successful than the treatment of drug sensitive strains. The goals of this proposed Program Project are to conduct a series of linked interdisciplinary research projects focused on the emergence and transmission of multidrug and extensively drug resistant tuberculosis and to support these projects through the development of a central core for administration and leadership, database management and a central M. tuberculosis isolate archive. Linked research projects include: a cohort study of host and microbial factors associated with the emergence and transmission of drug sensitive and resistant TB in Lima, Peru; a study designed to characterize M. tuberculosis strain diversity and its contribution to the emergence and spread of MDR; and a study to use epidemic and individual predictive models to support public health policy and clinical decision making for MDR and XDR tuberculosis. PROJECT 1: Host and microbial risk factors for drug-sensitive and -resistant tuberculosis Becerra, M Description (provided by applicant): M. tuberculosis is a highly successful pathogen that infects over eight million people per year and leads to over 2 million deaths. One third of the world's population is believed to be infected with this organism, but only a small minority of those infected will go on to develop active disease. Although some risk factors for disease progression have been described, host and microbial mechanisms that lead to increased susceptibility are poorly understood. The identification of factors associated with the transmission and progression of drug sensitive and resistant tuberculosis may provide targets for focused clinical and public health interventions. Such interventions will be of particular importance for the control of drug resistant tuberculosis, since current control measures focus on the effective treatment of infectious cases. The long term goals are to elucidate factors involved in the emergence and transmission of multidrug (MDR) and extensively drug resistant (XDR) tuberculosis and to develop and implement interventions that target these factors in order to reduce tuberculosis progression and transmission. The specific aims of this project are to identify host, microbial and environmental risk factors for the development of drug sensitive (DS) and MDR tuberculosis and to archive strains characterized on the basis of their epidemiologic and clinical behavior so that they can be used in basic research on strain diversity and its contribution to MDR. We will also establish a comprehensive database which will allow real-time surveillance and be used for epidemic modeling and individual prediction models that will assist decision making regarding the treatment of drug resistant tuberculosis.