Diagnosis of tuberculosis in the elderly

描述(申请人提供)：据估计，世界上三分之一的人口携带潜在形式的结核分枝杆菌(M.tb)感染。在免疫受损的任何给定时间，这一全球储存库都可能重新激活，从而导致活动性结核病。随着我们年龄的增长，免疫力发生了公认的变化，老年人是重新激活结核病的一个重要的Rick群体。到2050年，全球老年人口预计将增加两倍，达到近20亿，我们可以预计，老年人口将在未来重新激活的结核病病例中占据相当大的比例。在感染结核分枝杆菌的老年患者中进行的研究很少，我们所了解的大部分关于免疫功能的研究都是使用老年小鼠模型产生的，该模型更容易感染结核分枝杆菌，据报道CD4T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循环免疫细胞对结核分枝杆菌抗原的反应能力。干扰素伽马释放试验(IGRA)在结核病诊断中的应用已经取得了进展，但IGRA与目前的老年人结核菌素皮肤试验(TST)相比，其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将提供对老年人结核分枝杆菌暴露的更准确的诊断，我们的发现可能会对老年人队列中进行结核病检测的方式产生直接影响。通过进行转化性研究，我们将解决特定的知识差距，以调查患有活动性结核病和潜伏的结核分枝杆菌感染的老年患者的免疫功能，这将使我们能够在不断扩大的人口中更好地诊断结核病。

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.