三种实验室诊断技术对结核分枝杆菌复合群检出率及检测费用的比较研究

目的 评估液基夹层杯涂片法(采用集菌法;简称“涂片法”)、L-J固体培养法(简称“L-J培养法”)、结核分枝杆菌复合群核酸检测(采用恒温扩增法;简称“恒温扩增法”)对结核分枝杆菌复合群的检测效能。 方法 采用随机数字表法从湖南省120家结核病定点医院中抽取3家作为研究现场,分别为浏阳市人民医院、醴陵市湘东医院、桃江县人民医院。以3家医院2018年11月1日至12月31日就诊的存在可疑肺结核症状的628例患者为研究对象,对同一份痰标本同时采用涂片法、L-J培养法和恒温扩增法进行检测,分析3种检测方法对结核分枝杆菌复合群阳性检出率的差异;并依据《WS 288—2017 肺结核诊断》的诊断标准,以临床诊断肺结核作为参考标准,计算各种检测方法的敏感度、特异度、阳性预测值、阴性预测值、一致率;再以患者进行每项检测的实际支出费用为准,计算每种方法的检测费用。结核分枝杆菌复合群检出率在3种检测技术间的两两比较采用χ ²检验,检验水准α=0.05/3=0.017。 结果 628例疑似肺结核患者中,临床确诊为肺结核患者153例(24.4%),NTM肺病患者6例(1.0%)。3种技术检测结果显示,涂片法、L-J培养法和恒温扩增法的结核分枝杆菌复合群阳性检出率(排除6例NTM肺病患者)分别为13.5%(84/622)、14.0%(87/622)和12.2%(76/622),涂片法和L-J培养法,L-J培养法和恒温扩增法,涂片法和恒温扩增法之间比较,差异均无统计学意义(χ ²=1.32,P=0.359;χ ²=5.83,P=0.024;χ ²=4.00,P=0.077)。以临床诊断结果作为参考标准,排除6例非结核分枝杆菌肺病患者和32例培养污染的患者,涂片法、L-J培养法和恒温扩增法的敏感度分别为55.2%(80/145)、57.9%(84/145)、50.3%(73/145);特异度分别为99.6%(443/445)、99.3%(442/445)、99.8%(444/445);阳性预测值分别为97.6%(80/82)、96.6%(84/87)、98.6%(73/74);阴性预测值分别为87.2%(443/508)、87.9%(442/503)、86.0%(444/516);一致率分别为88.6%(523/590)、89.2%(526/590)、87.6%(517/590)。3种方法的检测费用,由低到高依次为L-J培养法[317.2元(29500/93)]、涂片法[813.8元(70800/87)]、恒温扩增法[1992.2元(153400/77)]。 结论 涂片法、L-J培养法、恒温扩增法的阳性检出率及其敏感度和特异度均未见差异。平均发现1例病原学阳性结核病患者的检测费用,L-J培养法较低,恒温扩增法较高。

Comparative study on detection rate and detection cost of Mycobacterium tuberculosis complex by three laboratory diagnostic techniques

Objective To evaluate the detection efficiency of Mycobacterium tuberculosis complex by liquid-based interlayer (using the method of collecting bacteria, referred to as “smear method”), L-J solid culture method (referred to as “L-J culture method”) and nucleic acid detection of Mycobacterium tuberculosis complex group (using constant temperature amplification method; referred to as “thermostatic amplification method”). +++ Methods--- Three hospitals were randomly selected as research sites from the 120 tuberculosis designated hospitals using random number table, including Liuyang People’s Hospital, Liling Xiangdong Hospital, and Taojiang County People’s Hospital. A total of 628 patients with suspected tuberculosis symptoms diagnosed in 3 hospitals from November 1 to December 31, 2018 were included as the research subjects. The same sputum specimens were tested by smear method, L-J culture method, and thermostatic amplification method, and then the difference of positive detection rate of Mycobacterium tuberculosis complex by 3 testing methods was analyzed. In addition, according to the diagnostic criteria of 《WS 288-2017 Pulmonary Tuberculosis Diagnosis》, the clinical diagnosis of tuberculosis was used as the reference standard, and the sensitivity, specificity, positive predictive value, negative predictive value and consistency of the 3 testing methods were calculated. Based on the actual expenditure of each test performed by the patient, the testing cost of each method was calculated. Comparison of detection rate of Mycobacterium tuberculosis complex among three methods was used by Chi square test, test level α=0.05/3=0.017. Results Among 628 patients with suspected pulmonary tuberculosis, there were 153 (24.4%) patients clinically diagnosed with pulmonary tuberculosis and 6 (1.0%) patients with non-tuberculous mycobacterium pulmonary disease. The results of 3 testing methods showed that the positive detection rates of Mycobacterium tuberculosis complex by smear method, L-J culture method, and thermostatic amplification method (excluding 6 patients with non-tuberculous mycobacterium pulmonary disease) were 13.5% (84/622), 14.0% (87/622), and 12.2% (76/622), respectively. The difference of positive rate of Mycobacterium tuberculosis complex among the three test methods was not statistically significant (smear method vs. L-J culture method: χ ²=1.32, P=0.359; L-J culture method vs. thermostatic amplification method: χ ²=5.83, P=0.024; smear method vs. thermostatic amplification method: χ ²=4.00, P=0.077). Based on the clinical diagnosis as the reference standard, for smear method, L-J culture method, and thermostatic amplification method (excluding 6 patients with non-tuberculous mycobacterium pulmonary disease and 32 patients with contaminated culture), the sensitivity was 55.2% (80/145), 57.9% (84/145) and 50.3% (73/145), respectively; the specificity was 99.6% (443/445), 99.3% (442/445) and 99.8% (444/445), respectively; the positive predictive value was 97.6% (80/82), 96.6% (84/87) and 98.6% (73/74), respectively; the negative predictive value was 87.2% (443/508), 87.9% (442/503) and 86.0% (444/516), respectively; and the coincidence rate was 88.6% (523/590), 89.2% (526/590) and 87.6% (517/590), respectively. The cost of three methods was calculated from low to high in order: L-J culture method: 317.2 yuan (29 500/93), smear method: 813.8 yuan (70800/87), and thermostatic amplification method: 1992.2 yuan (153400/77). Conclusion There is no difference among the three detection methods in terms of positive detection rate, sensitivity and specificity. When a patient with positive etiology is found, L-J culture method has the lowest cost, while thermostatic amplification method has the highest cost.