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

Background
Current 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.
Objective
To 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.
Methods
Between 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.
Results
Of 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).
Conclusion
The 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
当前肺结核诊断方法灵敏度不足且成本高昂。在HIV感染率较高的资源匮乏地区，亟需精准、快速且低成本的诊断试剂用于床旁检测。

研究目的
本研究旨在对比环介导等温扩增（loop-mediated isothermal amplification, LAMP）检测、Xpert® MTB/RIF以及荧光涂片显微镜检查在慢性咳嗽成人肺结核诊断中的灵敏度、特异度及检测成本。

研究方法
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人进行咳嗽筛查，为其提供HIV检测，并通过LAMP、Xpert® MTB/RIF及荧光涂片显微镜检查评估肺结核感染情况。以培养法作为金标准，估算三种检测方法的灵敏度、特异度及检测成本。

研究结果
本研究共纳入273名成人受试者，其中44.3%（121/273）为HIV阳性，19.4%（53/273）经细菌学确诊为肺结核。以培养法为金标准时，LAMP的灵敏度为65.0%（95%置信区间：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的灵敏度无显著差异（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。当批处理样本量为14份时，LAMP的单样本检测成本最低，为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诊疗政策，该政策推荐对HIV感染者、已确诊涂片阴性者或拟接受肺结核复治的人群，优先采用荧光涂片显微镜检查与Xpert® MTB/RIF联合检测方案。