MOLECULAR EPIDEMIOLOGY OF TUBERCULOSIS IN THE HOMELESS

结核病控制的有效性取决于了解 结核病在高患病率人群中的发病机制。因为大多数 在美国，肺结核被认为是由于 对于既往感染，控制工作强调化学预防， 无症状结核感染。 我们假设， 结核病比以前假设的要普遍得多， 特定的宿主因素有利于结核病的快速发展， 感染疾病。 如果这一假设是正确的， 积极开展病例发现和环境控制， 疾病传播。 我们将用DNA来检验这个假设 指纹鉴定法评估结核病在非洲的传播模式 城市无家可归者此外，我们亦建议加强侦查 通过基于PCR的DNA指纹分析来检测结核病疫情。 我们的具体 目的是：1）确定原发性结核病对 无家可归者的结核病发病率。这将通过DNA实现 250例连续无家可归者结核分枝杆菌分离株的指纹分析 洛杉矶中心的患者，与来自稳定居住的分离株相比， 年龄、性别、人种和种族匹配的患者。 2.1)以识别 常见原发性结核病的地点。这将是 通过关联详细的流行病学和临床数据， 无家可归的肺结核患者的DNA指纹图谱结果。2.2)到 确定促进初级保健发展的主要因素 结核 特定宿主因子在 有利于原发性结核病的发展将由以下因素决定 将这些因素在无家可归患者中的分布与 原发性结核病和无家可归的非结核病患者。 3)为了评估混合接头DNA指纹图谱的实用性， 减少结核病传播的有针对性的干预措施。 混合 基于PCR扩增的分枝杆菌接头DNA指纹图谱 DNA，将适用于临床样本和早期分枝杆菌 培养，然后前瞻性地应用于所有结核分枝杆菌分离株， 洛杉矶中心无家可归的肺结核患者。结合 目标2中获得的信息，这将有助于快速识别 结核病暴发，并允许针对以下人群采取干预措施： 具体地点和患者人群，以减少疾病传播。

The efficacy of tuberculosis control hinges on understanding the pathogenesis of tuberculosis in high-prevalence populations. Because most tuberculosis in the United States is thought to result from reactivation of prior infection, control efforts emphasize chemoprophylaxis for asymptomatic tuberculous infection. We hypothesize that primary tuberculosis is much more common than has been previously assumed, and that specific host factors favor rapid progression of tuberculous infection to disease. If this hypothesis is correct, more emphasis should be given to active case-finding and environmental controls to reduce disease transmission. We will test this hypothesis by using DNA fingerprinting to evaluate patterns of tuberculosis transmission in the urban homeless. In addition, we propose to facilitate detection of tuberculosis outbreaks through PCR-based DNA fingerprinting. Our specific aims are: 1) To determine the contribution of primary tuberculosis to tuberculosis morbidity in the homeless. This will be achieved by DNA fingerprinting of M tuberculosis isolates from 250 consecutive homeless patients in central Los Angeles, compared to isolates from stably housed patients, matched for age, sex, race and ethnicity. 2.1) To identify sites where development of primary tuberculosis is common. This will be achieved by correlating detailed epidemiologic and clinical data on homeless tuberculosis patients with results of DNA fingerprinting. 2.2) To identify the host factors that contribute to development of primary tuberculosis. The relative importance of specific host factors in favoring development of primary tuberculosis will be determined by comparing the distribution of these factors in homeless patients with primary tuberculosis and homeless control patients without tuberculosis. 3) To evaluate the utility of mixed linker DNA fingerprinting to direct targeted interventions that reduce tuberculosis transmission. Mixed linker DNA fingerprinting, based on PCR amplification of mycobacterial DNA, will be adapted for use on clinical samples and early mycobacterial cultures, then prospectively applied to all M tuberculosis isolates from homeless tuberculosis patients in central Los Angeles. In combination with the information obtained in aim 2, this will allow rapid recognition of unsuspected tuberculosis outbreaks and allow interventions targeted at specific sites and patient populations to reduce disease transmission.