Diagnosis of tuberculosis in the elderly

描述（由申请人提供）：据估计，世界上三分之一的人口携带潜伏型结核分枝杆菌（M.tb）感染。这种全球性的储存库可以在免疫力受损的任何特定时间重新激活，导致活动性结核病。随着年龄的增长，免疫力发生了公认的变化，老年人是结核病复发的重要危险群体。预计到2050年，全球老年人口将增加两倍，达到近20亿，我们可以预期，老年人将在未来的肺结核复发病例中占很大比例。在结核分枝杆菌感染的老年患者中进行的研究很少，我们对免疫功能的了解大部分是使用老年小鼠模型产生的，老年小鼠模型更容易感染结核分枝杆菌，据报道CD4 T细胞功能较差。随着新的结核分枝杆菌暴露诊断试剂盒的出现，我们现在可以直接测试老年结核病患者的循环免疫细胞对结核分枝杆菌抗原的反应能力。在结核病诊断中使用干扰素γ释放试验（IGRA）是一种趋势，但IGRA与目前的结核菌素皮肤试验（TST）在老年人中的敏感性和适用性尚未得到测试。我们的建议将填补这一关键的知识空白。我们预测，IGRA将提供一个更准确的诊断结核分枝杆菌暴露在老年人和我们的研究结果可能会立即影响的方式，结核病检测是在老年人队列。通过进行转化研究，我们将解决一个特定的知识差距，以调查活动性结核病和潜伏性结核分枝杆菌感染的老年患者的免疫功能，这将使我们能够更好地诊断结核病在这个不断扩大的人口。 公共卫生相关性：老年人更容易感染M。结核病是一种常见的疾病，但由于结核菌素皮肤试验（TST）在老年诊断价值低，因此对这一特定人群的诊断具有挑战性。随着新的体外诊断试剂盒的出现，以确定结核分枝杆菌暴露，有必要比较这些新的测试在老年人队列的敏感性和适用性。我们的研究将填补这一特定的知识空白，并可能对老年人结核分枝杆菌的诊断产生直接的临床影响。

DESCRIPTION (provided by applicant): It is estimated that one third of the world's population carries a latent form of Mycobacterium tuberculosis (M.tb) infection. This global reservoir can reactivate at any given time that immunity is compromised, leading to active TB disease. With the recognized changes in immunity that occur as we grow older, the elderly are a significant rick group for reactivation TB. With the global elderly population projected to triple to almost 2 billion by the year 2050 we can anticipate that the elderly will make up a significant portion of al reactivation TB cases in the future. Few studies have been performed in M.tb infected elderly patients and much of what we understand about immune function has been generated using the aged mouse model, which is more susceptible to infection with M.tb and is reported to have poor CD4 T cell function. With the advent of new diagnostic kits for M.tb exposure we can now directly test the capacity of circulating immune cells from elderly TB patients to respond to M.tb antigens. There is a move towards the use of interferon gamma release assays (IGRA) in TB diagnosis, yet the sensitivity and applicability of IGRA versus the current tuberculin skin test (TST) in elderly individuals has not been tested. Our proposal will fill this critical gap in knowledge. We predict that the IGRA will provide a more accurate diagnosis of M.tb exposure in elderly individuals and our findings are likely to have immediate impact on the way that TB testing is performed in elderly cohorts. By performing translational studies we will address a specific knowledge gap to investigate immune function in elderly patients with active TB and latent M.tb infection that will allow us to better diagnose TB in this expanding population. PUBLIC HEALTH RELEVANCE: The elderly are more susceptible to reactivation of an infection with M. tuberculosis yet diagnosis of this specific group is challenging due to the poor diagnostic value of the tuberculin skin test (TST) in old age. With the advent of new in vitro diagnostic kits to determine M.tb exposure, there is a need to compare the sensitivity and applicability of these new tests in an elderly cohort. Our studies will fill this specific knowledg gap and are likely to have an immediate clinical impact on the diagnosis of M.tb in elderly individuals.