Assessment by meta-analysis of PCR for diagnosis of smear-negative pulmonary tuberculosis

Abstract

We conducted a meta-analysis to assess the performance of PCR for the diagnosis of smear-negative pulmonary tuberculosis (SPT) and to identify factors that account for differences in the diagnostic accuracy of different studies. Studies published before February 2002 were included if sensitivity and specificity of PCR in smear-negative respiratory or gastric-aspirate specimens could be calculated. Analysis was conducted by using summary receiver operating characteristics models. Sensitivity and specificity ranged from 9 to 100% and from 25 to 100%, respectively. Fewer than 40% of the 50 studies reported results by number of patients, reported clinical characteristics of patients, or used as a reference standard combined culture and clinical criteria. Studies that included bronchial specimens showed higher accuracy than studies that evaluated only sputum specimens or included gastric aspirates. Studies that did not report that tests were applied blindly showed higher accuracy than those reporting blind testing. Increased sensitivity due to the use of DNA purification methods was associated with decreased specificity. Studies published after 1995, using Amplicor or dUTP-UNG, were associated with an increase in specificity at the expense of lower sensitivity. We concluded that PCR is not consistently accurate enough to be routinely recommended for the diagnosis of SPT. However, PCR of bronchial specimens could be useful in highly suspicious SPT cases. Studies not reporting blind testing are likely to overestimate accuracy of PCR. Future evaluation of PCR accuracy should be conducted by patient and type of respiratory specimen, blindly, by using a reference standard that combines culture and clinical criteria and addresses the issue of how patient characteristics affect PCR accuracy.

FIG. 1.

Point estimates and 95% confidence intervals of sensitivity and specificity of PCR for detection of M. tuberculosis in smear-negative respiratory and gastric specimens. Specimen studies included studies in which respiratory specimens (sputum, tracheal aspirates, bronchial washings, and bronchoalveolar lavage) were the unit of analysis. Patient studies included studies in which the patients, whose respiratory specimens were evaluated, were the unit of analysis. Gastric studies included studies in which gastric aspirates or respiratory specimens plus gastric aspirates were evaluated. The number of studies totals 51 because 1 study reported results by both gastric aspirates and respiratory specimens. The numbers in parentheses correspond to study references.

FIG. 2.

Plot in the ROC space of accuracy estimates for PCR for the detection of M. tuberculosis in smear-negative respiratory specimens. Each of the 16 studies that were analyzed by patients is indicated by a triangle. ROC curves are shown for studies that analyzed bronchial specimens or tracheal specimens (thin line), for studies that analyzed only sputum specimens (broken line), and for all 16 studies (thick line). The intersection of the diagonal line from the upper left corner to the lower right corner of the ROC space and the SROC curve corresponds to the maximum joint sensitivity and specificity value.