Reassessment of the positive predictive value and specificity of Xpert MTB/RIF: a diagnostic accuracy study in the context of community-wide screening for tuberculosis

Ho, Jennifer; Nguyen, Phuong Chi; Nguyen, Thu Anh; Tran, Khoa Hien; Nguyen, Son; Nguyen, Nhung Viet; Nguyen, Hoa B.; Luu, Khanh Boi; Fox, Greg J.; Marks, Guy B.

doi:10.1016/s1473-3099(16)30067-6

Cited by 28 publications

(13 citation statements)

References 14 publications

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“…10 , 11 , 12 However, the sensitivity of Xpert in our study was similar to or lower than other studies, whereas its specificity was similar to other studies. 13 , 14 We also found that the sensitivity of Xpert for patients with smear-positive TB was higher than that for patients with smear-negative TB, similar to previous studies. In our study, we created a two-step algorithm for rapid diagnosis of TB at the Chinese border to prevent TB spread in China.…”

supporting

confidence: 88%

A two-step algorithm for rapid diagnosis of active pulmonary tuberculosis in entry applicants using the T-SPOT.TB and Xpert MTB/RIF assays in Shanghai, China

Chen

Shen

Wang

et al. 2017

Emerging Microbes & Infections

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supporting

confidence: 88%

A two-step algorithm for rapid diagnosis of active pulmonary tuberculosis in entry applicants using the T-SPOT.TB and Xpert MTB/RIF assays in Shanghai, China

Chen

Shen

Wang

et al. 2017

Emerging Microbes & Infections

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“…In a routine context, such individuals may be tested with highly sensitive nucleic acid amplification tests as contacts of index cases or as part of targeted active case finding in special populations. Xpert has been reported to have a high specificity in the communitybased screening of healthy individuals; however, this was in a setting with a very low prevalence of previous TB (27). This requires confirmation in settings with a high burden of patients with previous TB.…”

Section: Discussionmentioning

confidence: 94%

False-Positive Xpert MTB/RIF Results in Retested Patients with Previous Tuberculosis: Frequency, Profile, and Prospective Clinical Outcomes

et al. 2018

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Globally, Xpert MTB/RIF (Xpert) is the most widely used PCR test for the diagnosis of tuberculosis (TB). Positive results in previously treated patients, which are due to old DNA or active disease, are a diagnostic dilemma. We prospectively retested sputum from 238 patients, irrespective of current symptoms, who were previously diagnosed to be Xpert positive and treated successfully. Patients who retested as Xpert positive and culture negative were exhaustively investigated (repeat culture, chest radiography, bronchoscopy with bronchoalveolar lavage, long-term clinical follow-up). We evaluated whether the duration since previous treatment completion, mycobacterial burden (the Xpert cycle threshold [ ] value), and reclassification of Xpert-positive results with a very low semiquantitation level to Xpert-negative results reduced the rate of false positivity. A total of 229/238 (96%) of patients were culture negative. Sixteen of 229 (7%) were Xpert positive a median of 11 months (interquartile range, 5 to 19 months) after treatment completion. The specificity was 93% (95% confidence interval [CI], 89 to 96%). Nine of 15 (40%) Xpert-positive, culture-negative patients reverted to Xpert negative after 2 to 3 months (1 patient declined further participation). Patients with false-positive Xpert results had a lower mycobacterial burden than patients with true-positive Xpert results ( , 28.7 [95% CI, 27.2 to 30.4] versus 17.6 [95% CI, 16.9 to 18.2]; < 0.001), an increased likelihood of a chest radiograph not compatible with active TB (5/15 patients versus 0/5 patients; = 0.026), and less-viscous sputum (15/16 patients versus 2/5 patients whose sputum was graded as mucoid or less; = 0.038). All patients who initially retested as Xpert positive and culture negative ("Xpert false positive") were clinically well without treatment after follow-up. The duration since the previous treatment poorly predicted false-positive results (a duration of ≤2 years identified only 66% of patients with false-positive results). Reclassifying Xpert-positive results with a very low semiquantitation level to Xpert negative improved the specificity (+3% [95% CI, +2 to +5%]) but reduced the sensitivity (-10% [95% CI, -4 to -15%]). Patients with previous TB retested with Xpert can have false-positive results and thus not require treatment. These data inform clinical practice by highlighting the challenges in interpreting Xpert-positive results, underscore the need for culture, and have implications for next-generation ultrasensitive tests.

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“…Unlike many other studies that only used culture as the reference comparator, we employed clinical diagnosis as the second and more powerful reference standard for performance analysis. Culture was considered as a highly deficient “gold standard” for TB diagnosis and might be inadequate for assessing the accuracy of molecular diagnostic assays that have a similar sensitivity to culture [( Banoo et al, 2010 ; Theron et al, 2013 ; Barnard et al, 2015 ; Bunyasi et al, 2015 ; Ho et al, 2016 ; Singh et al, 2016 ) and this study]. Previous studies using reference standards other than culture, with additional criteria that lead to a positive clinical diagnosis, have often shown a higher predictive value and specificity of Xpert MTB/RIF than that reported by studies using culture as reference standard ( Theron et al, 2011 ; Ho et al, 2016 ; Walters et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Evaluation of Xpert MTB/RIF Assay With Bronchoalveolar Lavage Fluid as a Single Test or Combined With Conventional Assays for Diagnosis of Pulmonary Tuberculosis in China: A Two-Center Prospective Study

et al. 2018

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Introduction: The Xpert MTB/RIF is recommended by the World Health Organization as a first line rapid test for the diagnosis of pulmonary tuberculosis (TB); however, China does not routinely use this test, partially due to the lack of a sufficient number of systematic evaluations of this assay in local patients. The aims of this study were to comprehensively assess the diagnostic performance of Xpert MTB/RIF, either alone or in combination with conventional assays for the diagnosis of pulmonary TB in adult Chinese patients.Methods: Xpert MTB/RIF tests were performed in 190 adult patients with suspected pulmonary TB, using bronchoalveolar lavage fluid (BALF) as test specimens. In parallel, conventional tests were carried out using the same BALF samples. Using two different reference standards, the performance of Xpert MTB/RIF, conventional assays and their combinations were evaluated.Results: Using mycobacterial culture as the reference comparator, Xpert MTB/RIF was found to be superior to smear-microscopy in detecting Mycobacterium tuberculosis. When final diagnosis, based on clinical criteria, was employed as the reference standard, Xpert MTB/RIF showed an even higher accuracy of 72.1%, supported by a sensitivity of 61.1% and specificity of 96.6%. Xpert MTB/RIF also demonstrated a powerful capability to identify pulmonary TB cases undetected by culture or smear-microscopy. Combining smear-microscopy and Xpert MTB/RIF was found to be the most accurate early predictor for pulmonary TB. Rifampicin resistance reported by Xpert MTB/RIF slightly deviated from that by phenotypic antibiotic susceptibility testing and requires further study with a larger sample size.Conclusion: This two-center prospective study highlights the value of Xpert MTB/RIF with BALF in diagnosing pulmonary TB in adult Chinese patients. These findings might contribute to the optimization of current diagnostic algorithms for pulmonary TB in China.

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Reassessment of the positive predictive value and specificity of Xpert MTB/RIF: a diagnostic accuracy study in the context of community-wide screening for tuberculosis

Cited by 28 publications

References 14 publications

A two-step algorithm for rapid diagnosis of active pulmonary tuberculosis in entry applicants using the T-SPOT.TB and Xpert MTB/RIF assays in Shanghai, China

A two-step algorithm for rapid diagnosis of active pulmonary tuberculosis in entry applicants using the T-SPOT.TB and Xpert MTB/RIF assays in Shanghai, China

False-Positive Xpert MTB/RIF Results in Retested Patients with Previous Tuberculosis: Frequency, Profile, and Prospective Clinical Outcomes

A Comprehensive Evaluation of Xpert MTB/RIF Assay With Bronchoalveolar Lavage Fluid as a Single Test or Combined With Conventional Assays for Diagnosis of Pulmonary Tuberculosis in China: A Two-Center Prospective Study

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