Extensively Drug-Resistant Tuberculosis Among Gold Miners in South Africa

描述（由申请人提供）：高度耐药结核病（TB），包括多药耐药（MDR）和广泛耐药（XDR）结核病（统称为M/XDR-TB）对个人健康、公共卫生和结核病控制构成严重的全球威胁，特别是在艾滋病毒高流行的环境中。然而，人们对耐多药/广泛耐药结核病的流行病学，或其发现、监测、临床管理和预防的最佳策略知之甚少。南非的金矿工人感染了流行的艾滋病毒，并且患各种形式结核病的风险很高。本提案的总体目标是确定南非金矿工人研究人群中耐多药/广泛耐药结核病的特征，并确定检测广泛耐药结核病的最佳策略。我们的目标是确定耐多药/广泛耐药结核病的发病率、所有结核病病例的患病率、危险因素、传播模式和这一人群的临床结果。此外，我们将评估用于检测患者个体耐多药/广泛耐药结核病的三种快速诊断检测方法的实验室性能特点，确定并比较这些检测方法的成本和可行性，并使用数学建模来估计在人群层面检测广泛耐药结核病的各种策略的影响。研究人群的艾滋病毒患病率约为24-30%，结核病病例通报率超过每10万人4000例，几乎是南非其他地区的10倍。因此，拟议的研究人群是撒哈拉以南非洲广泛耐药结核病的重要哨点人群。拟议的研究将利用有效应对艾滋病/结核病流行联盟（CREATE）的Thibela结核病项目的有利框架进行。研究环境将是包括Thibela结核病项目在内的20个金矿，相关人口约为7万名员工。应用目标将通过开展一系列与耐药结核病前瞻性实验室监测规划相关的相互关联的研究来实现。前瞻性实验室监测计划将用于（根据药物敏感性状况）识别和确定总体研究人群中所有结核病患者的特征。这组结核病患者将作为确定耐多药/广泛耐药结核病的临床和人口危险因素、结果和传播模式的研究人群。此外，实验室监测方案将包括对检测利福平耐药性的新的快速检测方法的评估，并提供与未来开发用于快速检测氟喹诺酮类药物耐药性的分子检测方法有关的数据。从个人和公共卫生的角度来看，该研究项目提供的信息将非常重要，并直接响应世卫组织广泛耐药结核病全球工作队确定的研究重点。该项目提供的信息对于指导撒哈拉以南非洲和其他结核病/艾滋病毒高流行地区耐多药/广泛耐药结核病的预防、诊断和临床管理战略具有宝贵价值。

DESCRIPTION (provided by applicant): Highly drug-resistant tuberculosis (TB), including multidrug-resistant (MDR) and extensively drug- resistant (XDR) TB (collectively termed M/XDR-TB) represents a serious global threat to individual health, public health, and TB control, particularly in settings of high HIV prevalence. Yet, little is known about the epidemiology of M/XDR-TB, or optimal strategies for its detection, surveillance, clinical management, and prevention. Gold miners in South Africa have epidemic HIV infection and a high risk for all forms of TB. The overall goals of this proposal are to characterize M/XDR-TB in the study population of gold miners in South Africa, and to determine optimal strategies for detection of XDR-TB. Our objectives are to determine M/XDR-TB incidence, prevalence among all TB cases, risk factors, transmission patterns, and clinical outcomes in this population. In addition, we will evaluate laboratory performance characteristics of three rapid diagnostic tests for detection of M/XDR-TB in individual patients, determine and compare costs and feasibility of these tests, and use mathematical modeling to estimate the impact of various strategies for detection of XDR-TB at the population level. The study population has an HIV prevalence of approximately 24-30%, and TB case notification rates exceed 4000 per 100,000, almost 10-fold greater than for the rest of South Africa. Therefore, the proposed study population is an important sentinel population for XDR-TB in sub-Saharan Africa. The proposed studies will be performed using the enabling framework of the Thibela TB Project of the Consortium to Respond Effectively to the AIDS/TB Epidemic (CREATE). The study setting will be the 20 gold mine shafts with the associated population of ~70,000 employees that comprise the Thibela TB project. Application goals will be met through performance of a series of inter-related studies linked to a program of prospective laboratory surveillance for drug-resistant TB. The program of prospective laboratory surveillance will serve to identify and characterize (by drug-susceptibility status) all TB patients in the overall study population. This group of TB patients will serve as the study population for identification of clinical and demographic risk factors, outcomes, and transmission patterns of M/XDR-TB. In addition, the program of laboratory surveillance will incorporate an evaluation of new rapid tests for detection of rifampin resistance, and provide data relevant to future development of molecular tests for rapid detection of fluoroquinolone resistance. Information from this research project will be highly important from perspectives of individual and public health, and is directly responsive to research priorities identified by the WHO Global Task Force on XDR-TB. Information from this project will be invaluable for guiding strategies for prevention, diagnosis, and clinical management of M/XDR-TB throughout sub-Saharan Africa and other areas of high TB/HIV prevalence. PUBLIC HEALTH AND RELEVANCE: This project is relevant to public health because information from the project will guide development of strategies for prevention, diagnosis, and clinical management of M/XDR-TB patients throughout sub-Saharan Africa and other areas of high TB/HIV prevalence. This project is directly responsive to research priorities identified by the World Health Organization Global Task Force on XDR-TB. Specifically, identification of M/XDR-TB risk factors and transmission patterns will guide development of prevention strategies; rigorous assessment of rifampin resistance tests will guide development and implementation of optimal diagnostic strategies; and identification of factors associated with clinical outcomes will inform strategies for clinical management of M/XDR-TB patients.