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

“虽然结核病的病因结核分枝杆菌感染得到了广泛的研究，但非结核分枝杆菌（NTM）在环境中更为常见，但通常不会引起任何人类健康问题。然而，它们在免疫系统受损的患者中是一个重要问题。因此，高达10- 20%的囊性纤维化患者感染了结核分枝杆菌。感染会阻止移植，并在病人之间传播，需要隔离;治疗可能需要两年时间--失败的可能性为60%。这个问题是如此严重，以至于目前所有的患者都要接受筛查;这使用了一种昂贵的方法，因为患者可能在检测中呈阳性，但没有显示出临床疾病。** 一种快速、具有成本效益的诊断方法，还可以监测感染和治疗的进展，这对临床医生来说将是一个重大变化。诊断有限公司 **在实验室中制备了一套分子，与分枝杆菌中复杂混合物的单个组分相同，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结核病，即使在已经接种疫苗或患有“潜伏”疾病的患者中也是如此。使用适当的抗原，它还可以检测牛结核病，并区分牛中的禽副结核分枝杆菌感染，这是约翰氏病的原因。本项目将确定，通过适当选择抗原，它可以提供一个快速，廉价的诊断感染的NTMs，证明使用_M. dumessus，_以及_M。avium_，囊性纤维化感染。该公司将使用其专有的抗原来评估没有感染的患者的血清，那些通过标准血液检测呈阳性但没有临床症状的患者，以及那些也显示出临床症状的患者。样本将由 ** 皇家Papworth医院 * Trust** 提供，并获得适当的伦理批准，Floto教授将提供有关试验开发的专家临床输入。"

"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."