Scherer Luciene Cardoso, Sperhacke Rosa Dea, Jarczewski Carla, Cafrune Patrícia I, Minghelli Simone, Ribeiro Marta Osório, Mello Fernanda Cq, Ruffino-Netto Antonio, Rossetti Maria Lr, Kritski Afrânio L
Programa de pós Graduação em Ciências Biológicas- Bioquímica, Universidade Federal do Rio Grande do Sul-UFRGS, Porto Alegre, RS, Brazil.
BMC Public Health. 2007 Dec 20;7:356. doi: 10.1186/1471-2458-7-356.
Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of Mycobacterium tuberculosis (MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection.
To evaluate the performance of the PCR dot-blot in parallel with pretest probability (Clinical Suspicion) in patients suspected of having SNPTB, a prospective study of 213 individuals with clinical and radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a TB/HIV reference hospital. Respiratory specialists estimated the pretest probability of active disease into high, intermediate, low categories. Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining), culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture positivity combined with the clinical definition of PTB.
In smear-negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2% (19/45), respectively. In the high, intermediate and low pretest probability categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80), respectively. PCR had sensitivity of 65% (CI 95%: 50%-78%) and specificity of 83% (CI 95%: 75%-89%). There was no difference in the sensitivity of PCR in relation to HIV status. PCR sensitivity and specificity among non-previously TB treated and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI 95%:57%-84%) and specificity of 86% (CI 95%:78%-92%). Using the PCR dot-blot in parallel with high pretest probability as a diagnostic test, sensitivity, specificity, positive and negative predictive values were: 90%, 71%, 75%, and 88%, respectively. Among non-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively.
PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital.
在发展中国家，涂片阴性肺结核（SNPTB）占每年报告的肺结核（PTB）病例的30%。聚合酶链反应（PCR）可能为快速检测结核分枝杆菌（MTB）提供一种替代方法；然而，在结核/艾滋病病毒合并感染负担较高的情况下，关于PCR在SNPTB中的临床效用的数据很少。
为了评估PCR斑点印迹法与疑似SNPTB患者的检测前概率（临床怀疑）的并行性能，2003年5月至2004年5月在一家结核/艾滋病病毒参考医院对213例临床和影像学疑似SNPTB的个体进行了一项前瞻性研究。呼吸专科医生将活动性疾病的检测前概率估计为高、中、低三类。对咳出的痰液进行直接显微镜检查（萋-尼染色）、培养（罗氏培养基）和PCR斑点印迹法检测。金标准基于培养阳性结合PTB的临床定义。
在涂片阴性且未感染艾滋病病毒的受试者中，活动性PTB的诊断率分别为28.4%（43/151）和42.2%（19/45）。在检测前概率高、中、低三类中，活动性PTB的诊断率分别为67.4%（31/46）、24%（6/25）、7.5%（6/80）。PCR的敏感性为65%（95%可信区间：50%-78%），特异性为83%（95%可信区间：75%-89%）。PCR的敏感性与艾滋病病毒感染状况无关。在既往未接受过结核病治疗的患者和既往接受过治疗的患者中，PCR的敏感性和特异性分别为：69%、43%、85%和80%。高检测前概率用作诊断试验时，敏感性为72%（95%可信区间：57%-84%），特异性为86%（95%可信区间：78%-92%）。将PCR斑点印迹法与高检测前概率并行用作诊断试验时，敏感性、特异性、阳性和阴性预测值分别为：90%、71%、75%和88%。在既往未接受过结核病治疗且感染艾滋病病毒的受试者中，这种方法的敏感性、特异性、阳性和阴性预测值分别为91%、79%、81%、90%，以及90%、65%、72%、88%。
与高度临床怀疑相关的PCR斑点印迹法可能对SNPTB的诊断做出重要贡献，主要是在结核/艾滋病病毒参考医院就诊的既往未接受过治疗的患者中。
