Pai Madhukar, Kalantri Shriprakash, Dheda Keertan
University of California, Berkeley & San Francisco, Berkeley Division of Epidemiology, 140, Warren Hall, Berkeley, CA 94720, USA.
Expert Rev Mol Diagn. 2006 May;6(3):413-22. doi: 10.1586/14737159.6.3.413.
Nearly a third of the world's population is estimated to be infected with Mycobacterium tuberculosis. This enormous pool of latently infected individuals poses a major hurdle for global tuberculosis (TB) control. Currently, diagnosis of latent TB infection (LTBI) relies on the tuberculin skin test (TST), a century-old test with known limitations. In this review, the first of a two-part series on new tools for TB diagnosis, recent advances in the diagnosis of LTBI are described. The biggest advance in recent years has been the development of in vitro T-cell-based interferon-gamma release assays (IGRAs) that use antigens more specific to M. tuberculosis than the purified protein derivative used in the TST. Available research evidence on IGRAs suggests they have higher specificity than TST, better correlation with surrogate markers of exposure to M. tuberculosis in low-incidence settings, and less cross-reactivity due to BCG vaccination than the TST. IGRAs also appear to be at least as sensitive as the purified protein derivative-based TST for active TB. In the absence of a gold standard for LTBI, sensitivity and specificity for LTBI are not well defined. Besides high specificity, other potential advantages of IGRAs include logistical convenience, avoidance of poorly reproducible measurements, such as skin induration, need for fewer patient visits and the ability to perform serial testing without inducing the boosting phenomenon. Overall, due to its high specificity, IGRAs may be useful in low-endemic, high-income settings where cross-reactivity due to BCG might adversely impact the utility of TST. However, despite the growing evidence supporting the use of IGRAs, several unresolved and unexplained issues remain. The review concludes by highlighting areas where evidence is lacking, and provides an agenda for future research. Active TB and drug resistance are discussed in Part II; 423-432 of this issue.
据估计，全球近三分之一的人口感染了结核分枝杆菌。如此庞大的潜伏感染人群给全球结核病控制带来了重大障碍。目前，潜伏性结核感染（LTBI）的诊断依赖于结核菌素皮肤试验（TST），这是一项有着百年历史且存在已知局限性的检测方法。在这篇综述中，作为关于结核病诊断新工具的系列文章的第一篇，将介绍LTBI诊断方面的最新进展。近年来最大的进展是基于体外T细胞的干扰素-γ释放试验（IGRAs）的开发，该试验使用的抗原比TST中使用的纯化蛋白衍生物对结核分枝杆菌更具特异性。关于IGRAs的现有研究证据表明，它们比TST具有更高的特异性，在低发病率地区与结核分枝杆菌暴露替代标志物的相关性更好，并且与TST相比，卡介苗接种引起的交叉反应更少。IGRAs对于活动性结核病的敏感性似乎也至少与基于纯化蛋白衍生物的TST一样高。在缺乏LTBI金标准的情况下，LTBI的敏感性和特异性尚无明确界定。除了高特异性外，IGRAs的其他潜在优势还包括后勤便利性、避免如皮肤硬结等重复性差的测量、患者就诊次数减少以及能够进行系列检测而不引发增强现象。总体而言，由于其高特异性，IGRAs可能在低流行、高收入环境中有用，在这些环境中，卡介苗引起的交叉反应可能会对TST的效用产生不利影响。然而，尽管支持使用IGRAs的证据越来越多，但仍有一些未解决和无法解释的问题。综述最后强调了证据不足的领域，并提供了未来研究的议程。活动性结核病和耐药性将在第二期第423 - 432页的第二部分中讨论。
