Low diagnostic accuracy of Xpert MTB/RIF assay for extrapulmonary tuberculosis: A multicenter surveillance

Abstract

Diagnostic accuracy of Xpert MTB/RIF assay for pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB) has not been investigated in Iran. This study was aimed to assess the diagnostic accuracy of Xpert MTB/RIF assay for both PTB and EPTB. A total of 2111 clinical samples (1218 pulmonary and 838 extra-pulmonary) were collected from 16 medical centers during the study period and were analyzed for detection of PTB and EPTB by both Xpert MTB/RIF assay and standard conventional methods (culture and direct smear microscopy). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Xpert MTB/RIF assay for PTB were found to be 95.5%, 96.7%, 83.8%, and 99.1% respectively. For EPTB, the sensitivity, specificity, PPV and NPV of Xpert MTB/RIF assay counted for 76.5%, 95.9%, 62%, and 97.9% respectively. Xpert MTB/RIF assay found to be highly sensitive, specific and comparable to standard conventional methods for the diagnosis of PTB. However, the sensitivity and specificity of Xpert MTB/RIF for EPTB specimens were highly variable; thus, Xpert MTB/RIF cannot be recommended to replace standard conventional tests for diagnosis of EPTB.

Figure 1

Forest plots give details of sensitivity, specificity, PPV, and NPV. BAL: bronchoalveolar lavage fluid, CSF: cerebrospinal fluid (Red colors are representative for pulmonary samples).

Figure 2

The summary receiver operating characteristic (SROC) curves for Xpert MTB/RIF assay. The SROC plot shows a summary of test performance, visual assessment of threshold effect, and heterogeneity of data in SROC space between sensitivity and specificity. The dashed blue line that is around the point estimate (blue line) shows 95% confidence region. The area under the curve (AUC), acts as an overall measure for test performance. Particularly, when AUC would be between 0.8 and 1, the accuracy is relatively high. As a matter of fact, AUC was 0.96 for pulmonary specimens in this report which represented a high level of accuracy. If SROC curve was in the upper left corner it would show the best combination of sensitivity and specificity for the diagnostic test. Part “a” and “b” are representative for pulmonary and extra-pulmonary specimens, respectively.

Figure 3

Quadratic regression plot to compare the Xpert MTB/RIF results with culture and smear microscopy. On Xpert MTB/RIF axis, results are categorized as 0, 1, 2, 3 and 4 which are indicated as negative, very low, low, medium and high scales, respectively. On the smear axis, results are categorized as 0, 1, 2 and 3 which are indicated as negative, 1+, 2+ and 3+ grading, respectively. On culture axis, results are categorized as 0, 1, 2, 3 and 4 which are indicated as negative, 1+, 2+, 3+ and 4+ grading, respectively. Part “a” and “b” are representative for pulmonary specimens and part “c” and “d” are representative for extra-pulmonary specimens. Regression lines showed the correlations between Xpert MTB/RIF results and culture/direct smear methods results.