Transmission of HIV-Associated XDR TB in Rural South Africa

南非农村地区艾滋病毒相关广泛耐药结核病的传播

• 批准号: 8240406
• 负责人: Nippie Sarita Shah
• 金额: $ 15.84万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-15 至 2012-08-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8240406
• 关键词: 14 year old; Address; Adherence; Advisory Committees; Affect; Area; Bacillus (bacterium); CD4 Lymphocyte Count; Chest; Communities; Contact Tracing; Country; Cross-Sectional Studies; Data; Diagnosis; Disease; Disease Outbreaks; Drug Resistant Tuberculosis; Drug resistance; Early Diagnosis; Enrollment; Epidemic; Epidemiologic Studies; Epidemiology; Exposure to; Extreme drug resistant tuberculosis; Fluoroquinolones; Future; Genotype; Goals; HIV; HIV Infections; HIV drug resistance; Health; Health Policy; Healthcare; Hospital Mortality; Hospitals; Immunocompromised Host; Immunosuppression; Individual; Infection; Infection Control; Injectable; Intervention; Investigation; Knowledge; Lead; Link; Location; Lung diseases; Malabsorption Syndromes; Measures; Methods; Molecular; Outcome; Pathway Analysis; Patients; Pattern; Perception; Persons; Pharmaceutical Preparations; Play; Population; Predisposition; Prevalence; Prevention; Province; Public Health; Relative (related person); Research; Research Priority; Resistance; Resources; Rifampin; Risk Factors; Role; Rural; Site; Social Network; South Africa; Sputum; Techniques; Testing; Therapeutic; Time; United States National Institutes of Health; Work; base; community setting; disorder prevention; evidence base; improved; insight; isoniazid; mortality; mutant; novel; population based; pressure; prevent; programs; prospective; public health relevance; response; rural area; sound; transmission process; tuberculosis drugs; tuberculosis treatment

DESCRIPTION (provided by applicant): Extensively drug-resistant tuberculosis (XDR TB) has emerged as a significant global epidemic and poses a particular threat to HIV-infected persons. Drug-resistant TB disease is predominantly thought to develop as a result of selection pressure for drug-resistant mutant bacilli ("amplified resistance"). Drug-resistant TB disease may also occur, however, from exposure to and infection with a TB strain which is already drug-resistant ("primary transmission"). Transmission of drug-resistant TB strains has been well-described in congregate settings, such as hospitals containing highly immunocompromised patients, but few studies have evaluated population-level transmission of drug-resistant TB, and none have done so in a high HIV prevalence setting. The collision of XDR TB and HIV in South Africa offers a unique, early opportunity to study these dual epidemics, which are anticipated to converge in other countries in the future. The current global crisis of drug-resistant TB is due to both amplified resistance and primary transmission, although the relative contribution of each is unknown. In Aim 1 of this application, we propose a prospective, population-based, cross-sectional study to determine the proportion of new XDR TB cases which develop due to primary transmission as opposed to amplified resistance in Tugela Ferry district, a rural area of South Africa with exceedingly high rates of XDR TB and HIV co-infection. We hypothesize that over three-quarters of XDR TB cases arise due to primary transmission. In Aim 2, we will combine molecular genotyping with contact tracing and social network analysis to provide insights into the relationships between XDR TB subjects with matching strain genotypes ("clusters") and the locations where TB transmission may be occurring. We expect to identify that transmission is occurring in not only healthcare, but also community congregate settings. The findings from this study will lead to a better understanding of XDR TB transmission patterns in the Tugela Ferry community, which is critical for targeting interventions to curb the ongoing XDR TB epidemic. The proposed study will be the first to integrate epidemiologic, molecular, and social network analytic methods to study TB transmission in a high HIV prevalence setting. The interactions between HIV infection and drug-resistant TB have been identified as a priority research area by the NIH and the Federal TB Task Force, specifically epidemiologic research and greater use of genotyping to improve understanding of HIV and drug-resistant TB, and implementation of intensive contact tracing and outbreak investigation. This application will address these issues directly and take place at the epicenter of the convergent epidemics of TB, HIV, and drug-resistant TB in rural South Africa, where our research group has been working since 2002. Continuous, population-level surveillance for XDR TB, including culture and drug-susceptibility testing for all TB suspects in Tugela Ferry district, creates a unique opportunity to study XDR TB transmission. PUBLIC HEALTH RELEVANCE: Effective prevention of XDR TB, a disease characterized by extremely high mortality, especially in HIV-infected patients, is crucial to controlling the current epidemic and will require understanding patterns of transmission in both healthcare and community settings. This study, which combines classic contact investigation with advanced molecular epidemiologic techniques and social network analysis, will examine XDR TB transmission patterns in a high-HIV-prevalent, rural, resource-limited setting. Findings will help improve the health of individuals and communities affected by the XDR TB epidemic and will create an evidence-base to guide sound public health policy for XDR TB disease prevention throughout the developing world.

描述（由申请人提供）：广泛耐药结核病（XDR TB）已成为一种重要的全球流行病，对艾滋病毒感染者构成特别威胁。耐药结核病主要被认为是由于耐药突变杆菌的选择压力（“扩大耐药性”）而发展起来的。然而，耐药性结核病也可能发生在接触和感染已经具有耐药性的结核菌株（“原发性传播”）。耐药结核菌株的传播在聚集环境中得到了很好的描述，例如有高度免疫功能低下患者的医院，但很少有研究评估耐药结核的人群水平传播，而且没有一项研究在艾滋病毒高流行环境中这样做。南非的XDR结核病和艾滋病毒的碰撞为研究这两种流行病提供了一个独特的早期机会，预计未来这两种流行病将在其他国家汇合。 目前的全球耐药结核病危机是由于扩大的耐药性和原发性传播造成的，尽管每一种的相对贡献尚不清楚。在本申请的目标1中，我们提出了一项前瞻性的、基于人群的、横断面研究，以确定在Tugela Ferry地区（南非农村地区，XDR TB和HIV合并感染率极高）由于原发性传播而不是扩增耐药性而发展的新XDR TB病例的比例。我们假设超过四分之三的XDR结核病例是由于原发性传播而出现的。在目标2中，我们将联合收割机分子基因分型与接触者追踪和社会网络分析相结合，以深入了解具有匹配菌株基因型（“簇”）的广泛耐药结核病受试者与可能发生结核病传播的地点之间的关系。我们希望确定传播不仅发生在医疗保健中，而且发生在社区聚集环境中。这项研究的结果将有助于更好地了解Tugela Ferry社区的XDR结核病传播模式，这对于有针对性的干预措施以遏制正在进行的XDR结核病流行至关重要。这项研究将是第一个整合流行病学、分子和社会网络分析方法来研究结核病在艾滋病毒高流行环境中的传播的研究。 美国国立卫生研究院和联邦结核病工作组已将艾滋病毒感染和耐药结核病之间的相互作用确定为优先研究领域，特别是流行病学研究和更多地使用基因分型以提高对艾滋病毒和耐药结核病的认识，以及实施密集的接触者追踪和疫情调查。这项应用将直接解决这些问题，并在南非农村结核病、艾滋病毒和耐药结核病的集中流行中心进行，我们的研究小组自2002年以来一直在那里工作。对广泛耐药结核病进行持续的人口水平监测，包括对图格拉费里地区所有结核病嫌疑人进行培养和药敏试验，为研究广泛耐药结核病传播创造了独特的机会。 公共卫生相关性：广泛耐药结核病是一种死亡率极高的疾病，特别是在艾滋病毒感染患者中，有效预防这种疾病对于控制目前的流行至关重要，需要了解医疗保健和社区环境中的传播模式。这项研究将传统的接触调查与先进的分子流行病学技术和社会网络分析相结合，将研究艾滋病毒高流行率、农村、资源有限环境中的XDR结核病传播模式。研究结果将有助于改善受广泛耐药结核病流行影响的个人和社区的健康，并将为指导整个发展中国家广泛耐药结核病预防的合理公共卫生政策建立证据基础。