Extensively Drug-Resistant Tuberculosis Among Gold Miners in South Africa

南非金矿工人患有广泛耐药结核病

• 批准号: 8111830
• 负责人: Susan E Dorman
• 金额: $ 66.07万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-18 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111830
• 关键词: Acquired Immunodeficiency Syndrome; Advisory Committees; Africa South of the Sahara; Area; Characteristics; Clinical; Clinical Management; Complement; Cross-Sectional Studies; DNA Sequence; Data; Databases; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Drug Resistant Tuberculosis; Drug resistance; Employee; Epidemic; Epidemiology; Evaluation; Extreme drug resistant tuberculosis; Fingerprint; Fluoroquinolones; Future; Genotype; Goals; Gold; HIV; HIV Infections; Health; Healthcare Industry; Incidence; Individual; Infection; Interruption; Interview; Laboratories; Link; Location; Mining; Molecular; Molecular Diagnostic Testing; Multi-Drug Resistance; Mutation Detection; Mycobacterium tuberculosis; Notification; Outcome; Patients; Pattern; Performance; Pharmaceutical Preparations; Population; Population Study; Predisposition; Prevalence; Prevention; Prevention strategy; Public Health; Records; Reporting; Research Priority; Research Project Grants; Resistance; Rest; Rifampicin resistance; Rifampin; Risk Factors; Sentinel; Series; Site; Source; South Africa; Specimen; Testing; Treatment Failure; Tuberculosis; World Health Organization; base; cost; fluoroquinolone resistance; health record; high risk; isoniazid; mathematical model; meetings; mortality; mycobacterial; programs; prospective; public health relevance; rapid detection; resistant strain; respiratory; response; surveillance data; surveillance strategy; transmission process; trend; tuberculosis treatment

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.

描述（由申请人提供）：高度耐药的结核病（TB），包括抗多药（MDR）和广泛的抗药性（XDR）TB（统称为M/XDR-TB），这代表了对个人健康，公共卫生和TB控制的严重威胁，尤其是在高HIV Prepartiess的情况下，尤其是对个人健康，公共卫生和TB的控制。然而，对于M/XDR-TB的流行病学或其检测，监视，临床管理和预防的最佳策略知之甚少。南非的黄金矿工患有流行艾滋病毒感染，所有形式的结核病都有高风险。该提案的总体目标是在南非的黄金矿工研究人群中表征M/XDR-TB，并确定检测XDR-TB的最佳策略。我们的目标是确定该人群中所有结核病病例，风险因素，传播模式和临床结果的M/XDR-TB发病率。此外，我们将评估三种快速诊断测试的实验室性能特征，以检测单个患者中M/XDR-TB，确定和比较这些测试的成本和可行性，并使用数学建模来估计各种策略在人群水平上检测XDR-TB的影响。研究人群的HIV患病率约为24-30％，结核病病例通知率超过每10万人4000，几乎比南非其他地区大10倍。因此，拟议的研究人群是撒哈拉以南非洲XDR-TB的重要哨兵人群。拟议的研究将使用财团的Thibela TB项目的促成框架进行有效响应，以对AIDS/TB的流行有效反应（CREATE）。研究环境将是20个金矿轴，其中约有70,000名员工的相关人口包括Thibela TB项目。通过与一系列与预期实验室监视计划有关的相关研究进行的一系列相关研究将实现应用程序目标。前瞻性实验室监视计划将有助于识别和表征（通过药物敏感性状态）所有结核病患者。这组结核病患者将作为研究人群，以鉴定M/XDR-TB的临床和人口统计风险因素，结果和传播模式。此外，实验室监视计划将纳入对利福平抗性的新快速测试的评估，并提供与分子测试未来开发有关的数据，以快速检测氟喹诺酮耐药性。从个人和公共卫生的角度来看，该研究项目中的信息将非常重要，并且直接响应WHO全球XDR-TB全球工作队确定的研究优先级。该项目的信息对于指导整个撒哈拉以南非洲的M/XDR-TB的预防，诊断和临床管理的策略将是无价的。 公共卫生和相关性：该项目与公共卫生有关，因为该项目的信息将指导开发整个撒哈拉以南非洲的M/XDR-TB患者的预防，诊断和临床管理策略，以及TB/HIV高的其他领域。该项目直接响应世界卫生组织全球特遣部队在XDR-TB上确定的研究优先级。具体而言，M/XDR-TB风险因素和传输模式的识别将指导预防策略的发展；对利福平抵抗测试的严格评估将指导最佳诊断策略的开发和实施；与临床结果相关的因素的鉴定将为M/XDR-TB患者的临床管理策略提供信息。