柳叶刀传染病:科学家开发出诊断与HIV共感染的结核分歧杆菌试纸
丁香园 · 2012/02/23
来自美国、英国、南非的研究人员合作开发出一种酶联免疫吸附试纸,检测尿液标本结核分歧杆菌特异性成分抗原TB-LAM,即TB-LAM试纸。用该试纸进行一项描述性研究结果显示其具有较高的灵敏度,非常适合应用于筛查CD4偏低的HIV感染患者是否感染结核分歧杆菌。

导读:来自美国、英国、南非的研究人员合作开发出一种酶联免疫吸附试纸,检测尿液标本结核分歧杆菌特异性成分抗原TB-LAM,即TB-LAM试纸。用该试纸进行一项描述性研究结果显示其具有较高的灵敏度,非常适合应用于筛查CD4偏低的HIV感染患者是否感染结核分歧杆菌。

图为TB-LAM试纸,左为阳性结果,中右为阴性结果

目前,通过痰涂片显微镜检和常规的胸部x线诊断与HIV共感染的结核分歧杆菌精确度较低,而培养诊断法耗时、高价,在大多资源有限的地方也不易开展。来自美国、英国、南非的研究人员合作开发出一种酶联免疫吸附试纸,检测尿液标本结核分歧杆菌特异性成分抗原TB-LAM,即TB-LAM试纸。用该试纸进行一项描述性研究结果显示其具有较高的灵敏度,非常适合应用于筛查CD4偏低的HIV感染患者是否感染结核分歧杆菌。该项研究已发表于《柳叶刀传染病》3月刊上。

在本研究中,研究人员于两年间(2010.3.12-2011.4.20)在南非古古莱图共招募有602位需接受抗逆转率病毒治疗成年艾滋患者,其中542位提供痰液。所用方法有:痰涂片显微镜检,自动液体培养法,Xpert MTB/RIF检测试剂盒, TB-LAM试纸。其中经培养法检测为结核分歧杆菌阳性的定义为肺结核患者。研究人员通过单纯检测受试者尿液标本TB-LAM抗原或与痰涂片显微镜检联用,再与痰涂片显微镜检和Xpert MTB/RIF检测试剂盒对比,评价诊断结果的精确度。

经培养法检测,94位为结核分歧杆菌阳性(17.3%,95% CI 14.2-20.8)。最后的结果来自516位患者(CD4计数中位值为169.5/μL,IQR 100-233),85位培养法为阳性(其中24位痰涂片显微镜检为阳性,[28.2%, 95% CI 19.0-39.0])。TB-LAM试纸在半小时内便能显示结果,不同试纸检测同一标本的结果具有高度一致性(κ=0.97),试纸与ELISA实验相比,同样高度一致(κ=0.84),受试者CD4计数越低,灵敏度越高:<50 /μL为66.7%(95% CI 41.0-86.7),<100 /μL为51.7%(95% CI 32.5-70.6),<200 /μL为39.0%(95% CI 26.5-52.6),同时,在所有CD4分层中,特异性均大于98%。与痰涂片显微镜检联用时(其中之一检测为阳性),灵敏度有所增加,<50 /μL为72.2%(95% CI 46.5-90.3),<100 /μL为65.5%(95% CI 45.7-82.1),<200 /μL为52.5%(95% CI 39.1-65.7),与Xpert MTB/RIF检测试剂盒相比无统计学差异。

与现存的诊断方法相比,TB-LAM试纸具有一种简单,高效,低成本的优点。与痰涂片显微镜检联用,检出结果将会更好。

 

Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study

Dr Stephen D Lawn MD, Andrew D Kerkhoff MSc, Monica Vogt N Dip Med Tech, Prof Robin Wood FCP

Background: The diagnostic accuracy of sputum smear microscopy and routine chest radiology for HIV-associated tuberculosis is poor, and culture-based diagnosis is slow, expensive, and is unavailable in most resource-limited settings. We assessed the diagnostic accuracy of a urine antigen test Determine TB-LAM Ag (Determine TB-LAM; Alere, Waltham, MA, USA) for screening for HIV-associated pulmonary tuberculosis before antiretroviral therapy (ART).

Methods: In this descriptive study, consecutive adults referred to a community-based ART clinic in Gugulethu township, South Africa, were all screened for tuberculosis by obtaining sputum samples for fluorescence microscopy, automated liquid culture (gold-standard test), and Xpert MTB/RIF assays (Cepheid, Sunnyvale, CA, USA) and urine samples for the Clearview TB-ELISA (TB-ELISA; Alere, Waltham, MA, USA) and Determine TB-LAM test. Patients with Mycobacterium tuberculosis cultured from one or more sputum samples were defined as cases of tuberculosis. The diagnostic accuracy of Determine TB-LAM used alone or combined with sputum smear microscopy was compared with that of sputum culture and the Xpert MTB/RIF assay for all patients and subgroups of patients stratified by CD4 cell count.

Findings: Patients were recruited between March 12, 2010, and April 20, 2011. Of 602 patients enrolled, 542 were able to provide one or more sputum samples, and 94 had culture-positive tuberculosis (prevalence 17.4%, 95% CI 14.2—20.8). Complete results from all tests were available for 516 patients (median CD4 count, 169.5 cells per μL; IQR 100—233), including 85 culture-positive tuberculosis, 24 of whom (28.2%, 95% CI 19.0—39.0) had sputum smear-positive disease. Determine TB-LAM test strips provided results within 30 min. Agreement was very high between two independent readers of the test strips (κ=0.97) and between the test strips and TB-ELISA (κ=0.84). Determine TB-LAM had highest sensitivity at low CD4 cell counts: 66.7% (95% CI 41.0—86.7) at <50 cells per μL, 51.7% (32.5—70.6) at <100 cells per μL, and 39.0% (26.5—52.6) at <200 cells per μL; specificity was greater than 98% for all strata. When combined with smear microscopy (either test positive), sensitivity was 72.2% (95% CI 46.5—90.3) at CD4 counts less than 50 cells per μL, 65.5% (45.7—82.1) at less than 100 cells per μL, and 52.5% (39.1—65.7) at less than 200 cells per μL, which did not differ statistically from the sensitivities obtained by testing a single sputum sample with the Xpert MTB/RIF assay.

Interpretation: Determine TB-LAM is a simple, low-cost, alternative to existing diagnostic assays for tuberculosis screening in HIV-infected patients with very low CD4 cell counts and provides important incremental yield when combined with sputum smear microscopy.

文献下载:http://www.biodiscover.com/news/pathology/library/11136

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