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形式的结核分枝杆菌（M.tb）感染。这一全球病毒库可在免疫力受损的任何特定时间重新激活，从而导致活动性结核病。随着年龄的增长，免疫力会发生公认的变化，因此老年人是结核病再激活的重要高危人群。预计到2050年，全球老年人口将增加两倍，达到近20亿，我们可以预计，老年人将在未来所有结核病复发病例中占很大一部分。对感染结核分枝杆菌的老年患者进行的研究很少，我们对免疫功能的了解大多是使用老年小鼠模型产生的，老年小鼠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患者循环免疫细胞对结核分枝杆菌抗原的反应能力。有一种趋势是在结核病诊断中使用干扰素γ释放试验（IGRA），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重要的知识空白。我们预测IGRA将为老年人结核分枝杆菌暴露提供更准确的诊断，我们的研究结果可能对老年人群体进行结核检测的方式产生直接影响。通过开展转化性研究，我们将解决研究活动性结核病和潜伏性结核分枝杆菌感染老年患者免疫功能的特定知识差距，这将使我们能够更好地诊断这一不断扩大的人群中的结核病。

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.