Proof of concept for a rapid diagnosis of infection with non-tuberculous mycobacteria in immune compromised patients

“虽然结核病的起因--结核分枝杆菌的感染得到了广泛的研究，但非结核分枝杆菌在环境中更为常见，但通常不会对人类健康造成任何问题。然而，对于免疫系统受损的患者来说，它们是一个严重的问题。因此，多达10%-20%的囊性纤维化患者感染了脓肿分枝杆菌。感染阻止了移植，并在患者之间传播，需要隔离；治疗可能需要两年--失败的可能性为60%。这个问题如此严重，以至于目前所有的患者都要进行筛查；这种方法使用的是一种昂贵的方法，这是因为患者可以在检测中呈阳性，但不会显示出临床疾病。**一种快速、经济有效的诊断方法，也可以监测感染和治疗的进展，将代表着临床医生的一步变化。*诊断有限公司**已经在实验室准备了一套分子，与存在于分枝杆菌中的复杂混合物的个别成分相同，其详细组成具有特定物种的特征。这些分子与结核病患者血液中存在的抗体结合，这种抗原-抗体结合可以非常有效地识别活动性肺结核疾病，即使在已经接种疫苗或患有潜在疾病的患者中也是如此。有了合适的抗原，它还可以检测出牛的结核病，并区分出引起约翰氏病的牛的副结核-禽型分枝杆菌的感染。该项目将确定，通过适当选择抗原，它可以提供一种快速、廉价的非结核分枝杆菌感染诊断方法，在囊性纤维化中使用脓肿分枝杆菌和禽类分枝杆菌感染进行演示。该公司将使用其专有抗原来评估未感染患者的血清，那些通过标准血液分析呈阳性但没有临床体征的患者，以及那些也显示临床体征的患者。样品将由**皇家帕沃斯医院*信托**提供样品，并获得适当的伦理批准，有关分析开发的专家临床意见将由弗洛托教授提供。“

"Although infection with _Mycobacterium tuberculosis_, the cause of TB, is very widely studied, non-tuberculous mycobacteria (NTMs) are much more common in the environment but generally do not present any human health problems. However, they are a significant problem in patients whose immune systems are compromised. Thus, up to 10-20 % of cystic fibrosis patients are infected with _Mycobacterium abscessus_. Infection prevents transplantation, and is spread from patient to patient, requiring isolation; treatment can take two years - with a 60 % chance of failure. The problem is so severe that all patients currently are screened; this uses an expensive method, compromised because patients can be positive in the assay but not show clinical disease. **A rapid, cost effective method of diagnosis, which could also monitor the progression of infection and treatment, would represent a step change for clinicians.****Diagnostig Ltd.** has prepared, in the laboratory, a suite of molecules identical to individual components of complex mixtures present in mycobacteria, the detailed compositions of which are characteristic of a particular species. These molecules bind to antibodies present in the blood of patients with TB, and this antigen-antibody binding can very effectively identify active tuberculosis disease even in patients who have been vaccinated or have 'latent' disease. With appropriate antigens, it can also detect bovine TB and distinguish infection by _Mycobacterium avium_ paratuberculosis in cattle, the cause of Johne's disease. This project will establish that, by appropriate choice of antigens, it can provide a rapid, cheap diagnosis of infection by NTMs, demonstrated using _M.abscessus,_ and also _M. avium_, infection in cystic fibrosis. The company will use its proprietary antigens to evaluate sera from patients with no infection, those positive by standard blood assays but with no clinical signs, and those also showing clinical signs. Samples will be provided, with appropriate ethical approvals, by **Royal Papworth Hospital** **Trust** and expert clinical input on assay development will be provided by Prof. Floto."