The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi

BackgroundCurrent tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence.ObjectiveTo investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy.MethodsBetween October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated.ResultsOf 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65).ConclusionThe sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.背景：当前结核病诊断方法灵敏度欠佳且成本高昂。在人类免疫缺陷病毒（Human Immunodeficiency Virus, HIV）流行率较高的资源匮乏地区，亟需精准、快速且低成本的床旁诊断检测方案。 目的：本研究旨在对比环介导等温扩增（loop-mediated isothermal amplification, LAMP）检测、Xpert® MTB/RIF与荧光涂片显微镜检查，针对慢性咳嗽成年患者的结核病诊断灵敏度、特异度及检测成本。 方法：2013年10月至2014年3月期间，研究人员对某基层诊所的连续就诊成年患者开展咳嗽筛查，提供HIV检测服务，并采用LAMP、Xpert® MTB/RIF及荧光涂片显微镜检查评估其结核病感染情况。以培养法（culture）作为金标准，估算各检测方法的灵敏度、特异度及检测成本。 结果：本研究共纳入273名成年患者，其中44.3%（121/273）为HIV阳性，19.4%（53/273）经细菌学确诊为结核病。以培养法为金标准时，LAMP的灵敏度为65.0%（95%置信区间（confidence interval, CI）：48.3%~79.4%），特异度为100%（95%置信区间：98.0%~100%）。Xpert® MTB/RIF的灵敏度为77.5%（95%置信区间：61.5%~89.2%），与LAMP相当（p=0.132）。经常规双读片的浓缩荧光涂片显微镜检查灵敏度为87.5%（95%置信区间：73.2%~95.8%），显著高于LAMP（p=0.020）。三种检测方法的特异度均较高。LAMP的单份检测最低成本为14份样本批量下的9.98美元，低于Xpert® MTB/RIF的13.38美元，但高于荧光涂片显微镜检查的0.65美元。 结论：LAMP的灵敏度与Xpert® MTB/RIF相当，但低于荧光涂片显微镜检查；三种检测方法的特异度均较高。本研究结果支持马拉维的相关政策，该政策推荐对HIV感染者、已确诊涂片阴性者或拟接受结核病复治的患者，优先联合使用荧光涂片显微镜检查与Xpert® MTB/RIF进行检测。