Xpert MTB/RIF Results in Patients With Previous Tuberculosis: Can We Distinguish True From False Positive Results?

Abstract

One in 7 Xpert-positive retreatment patients were culture negative and potentially false positive. False positivity was associated with recent previous tuberculosis, high CT, and a chest radiograph not suggestive of active tuberculosis. Clinicians may consider awaiting confirmatory testing in retreatment patients with CT> 30; however, most false positives fall below this cut-point. Xpert can detect DNA from nonviable, nonintact bacilli.

Effect of previous treatment and sputum quality on diagnostic accuracy of Xpert® MTB/RIF

“…17 Previously treated TB patients are key to current WHO treatment algorithms because the prevalence of antituberculosis drug resistance is 5-10 times higher than in 'new' TB patients. Our findings are consistent with the initial case reports [6][7][8] and two recent studies from Lower Xpert specificity in previously treated TB Zimbabwe and South Africa, where Xpert specificity was respectively 87% and 92%. [7][8][9] These results collectively stand in contrast with the initial validation and implementation trials where Xpert achieved an overall specificity of 99%.…”

“…Our findings are consistent with the initial case reports [6][7][8] and two recent studies from Lower Xpert specificity in previously treated TB Zimbabwe and South Africa, where Xpert specificity was respectively 87% and 92%. [7][8][9] These results collectively stand in contrast with the initial validation and implementation trials where Xpert achieved an overall specificity of 99%. 1,4,5 We suspect that post-enrollment exclusions of AFB-positive, culturenegative patients and the inclusion of lower proportions of retreatment cases could have led to an overestimation of the specificity of Xpert in the initial trials.…”

“…25 Theron et al reported that approximately one of six Xpert-positive results in retreatment patients are false-positives due to nonviable M. tuberculosis DNA. 7 However, although mycobacterial cultures remain the most sensitive method of detection, the sample decontamination process prior to culture is inherently detrimental to mycobacterial viability, and, as a result, the overall sensitivity of culture is only 85%, and much lower in paucibacillary disease. 26,27 Furthermore, shortly after the initiation of anti-tuberculosis treatment, M. tuberculosis bacilli enter into a persister-like phenotype that renders them non-culturable in standard culture media, yet their viability is restored with enriched media.…”

“…5 However, recent studies in programmatic conditions have suggested lower specificities of Xpert in previously treated patients (~90%). [6][7][8][9] Patients with discordant cultureÀ, Xpertþ results are currently thought to have 'false-positive' Xpert results as a result of remnant, non-viable bacilli after anti-tuberculosis treatment. 8,9 However, despite its known impact on the yield of other diagnostic methods such as AFB smear microscopy and culture, [10][11][12] limited attention has been placed on the effect of sputum quality on Xpert diagnostic performance.…”

Diagnostic Accuracy of IS6110 Insertion Gene, <i>Hsp65</i>, and Xpert MTB/RIF for Rapid Diagnosis of Pulmonary Tuberculosis

“…In our study, one patient sample was positive with Xpert MTP/RIF and negative by culture, the test can detect M. tuberculosis DNA from either nonviable or non-intact bacilli [25], taking into account also the culture limitation. Many advantages of the Xpert MTB/RIF are, first, it is fast, the result can be obtained within 90 minutes, second, positive result reflect the true detection of M. tuberculosis rather than nontuberculous mycobacteria [25], third detection of Rifampicin resistant bacteria. Besides all these advantages, the test is expensive, one test cost about 18 USD, which is not suitable for low-income countries.…”