Cross-Border Dynamics of MDR/XDR-TB Epidemiology by HIV Status in Tijuana, Mexico

6.项目摘要/摘要 近三分之一的世界人口感染了结核分枝杆菌(Mtb)， 每年导致200万人死亡。在20世纪40年代开始研发抗结核病药物后， 结核病在美国的发病率开始下降，但在20世纪80年代随着结核病的到来而回升 艾滋病毒/艾滋病。今天，结核分枝杆菌的威胁演变为多重甚至广泛抗药性。 (耐多药/广泛耐药结核病)对结核病控制构成全球挑战。一例广泛耐药结核病患者的近期报告 登上国际航班是一个鲜明的提醒，结核病不尊重国界。最忙的 世界上的边境口岸(每天超过40,000次北向口岸)将两国 美国加利福尼亚州圣地亚哥和墨西哥不列颠哥伦比亚省提华纳的数百万居民，那里的结核病最高 墨西哥的发病率。1997年的一项调查发现，提华纳41%的结核病病例对At耐药 至少有一种药物和17%的人对通用药物异烟肼和利福平(MDR-TB)耐药 在墨西哥，药敏试验(DST)被推荐用于所有结核病病例，但很少见 由于成本的原因，执行。因此，墨西哥结核病的流行轨迹是 未知，但在圣地亚哥耐多药结核病病例中，墨西哥出生的患者比例很高 这表明提华纳的抗药性并没有下降。提华纳艾滋病毒发病率上升 有加剧问题的危险。这项研究的目的是描述药物的流行病学。 在艾滋病毒和美国/墨西哥边境的背景下，蒂华纳出现了耐药结核病。为了实现这一目标， 我们建议从所有新诊断的结核病病例(n=1800-1800)中分离结核分枝杆菌并进行基因分型。 2100)在提华纳为期3年以上，以实现以下目标：1)衡量 耐多药结核病患病率的变化并确定当前的广泛耐药结核病患病率；2)确定 与获得耐多药结核病相比，主要耐多药结核病传播是否有所增加 从治疗失败和评估与耐多药结核病相关的因素；以及3)特征 耐药与敏感结核分枝杆菌的传播动力学及分子相关性 蒂华纳和加利福尼亚州(2004年开始进行常规基因分型)的菌株，并描述了 独特的菌株从边界的一边移动到另一边。我们的目标是一致的 在USPHS的号召下，“通过药物敏感性测试、病例报告、 专科护理、感染控制和扩大能力。 发展中国家耐多药/广泛耐药结核病政策和突出结核病干预目标 美国/墨西哥边境地区的预防。这项研究不仅将为 美国主要边境地区耐药结核病的流行和传播，但产生结核分枝杆菌 隔离储存库以供将来研究，并建立能力以改进结核病控制。

6. Project Summary/Abstract Nearly a third of the world's population is infected with Mycobacterium tuberculosis (Mtb), resulting in 2 million deaths a year. After anti-TB drugs were developed starting in the 1940s, the incidence of TB in the US began to decline, only to resurge in the 1980s with the advent of HIV/AIDS. Today, the threat of Mtb evolving to become multi- or even extensively drug resistant (MDR/XDR-TB) poses global challenges to TB control. Recent reports of a patient with XDR-TB boarding an international flight is a stark reminder that TB does not respect borders. The busiest border crossing in the world (over 40,000 northbound crossings daily) loosely separates the >4 million residents of San Diego, CA, USA and Tijuana, BC, Mexico, which has the highest TB incidence in Mexico. After a 1997 survey found 41% of Tijuana's TB cases were resistant to at least one drug and 17% were resistant to isoniazid and rifampin (MDR-TB), universal drug susceptibility testing (DST) was recommended for all TB cases in Mexico, yet is rarely performed due to the cost. Consequently, the epidemiologic trajectory of TB in Mexico is unknown, but a high proportion of Mexican-born patients among San Diego's MDR-TB cases suggests that drug resistance in Tijuana has not declined. Increasing HIV incidence in Tijuana threatens to intensify the problem. The goal of this study is to describe the epidemiology of drug resistant TB in Tijuana in the context of HIV and the US/Mexican border. To achieve this goal, we propose DST and genotyping Mtb isolates from all newly diagnosed TB cases (n=1800- 2100) in Tijuana for over a 3-year period to address the following aims: 1) to measure the change in MDR-TB prevalence and determine the current XDR-TB prevalence; 2) to determine whether primary MDR-TB transmission has increased relative to MDR-TB acquisition resulting from treatment failure and evaluate factors associated with MDR-TB; and 3) to characterize transmission dynamics and molecular relatedness of drug-sensitive and drug-resistant Mtb strains in Tijuana and California (where routine genotyping began in 2004), and describe the movement of unique strains from one side of the border to the other. Our aims are consistent with the USPHS's call for "renewed vigilance through drug-susceptibility testing, case reporting, specialty care, infection control, and expanded capacity." The proposed study will inform testing policy for MDR/XDR-TB in a developing country and highlight intervention targets for TB prevention in the US/Mexico border region. This study will not only provide key insights into prevalence and transmission of drug-resistant TB at a major US border, but produce an Mtb isolate repository for future studies and build capacity for improved TB control.