Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid

Abstract

Rationale The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. Methods South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (~10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. Results 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18–41) to 0 (0–0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1–49) versus 7 (0–21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. Conclusions MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment.

Validation of a severity-of-illness score in patients with tuberculosis requiring intensive care unit admission

“…[2] We included a small proportion of cases (14/83) in which diagnoses were never microbiologically confirmed (diagnosed on clinical and radiological criteria). Although this is not an infrequent practice in studies from high endemic areas, [17] it may have introduced some bias.…”

To Study the Usefulness of Cbnaat (Cartridge Based Nuclear Acid Amplification Test) in Bal (Bronchoalveolar Lavage) Samples in the Diagnosis of Smear-Negative/Non Sputum Producing Patients With Suspected Tuberculosis

“…15 Theron et al In their study of 154 patients in a South-African single-centre study analysed the BAL samples in which sensitivity and specificity values compared to the culture were 92.6% and 96.0% for the Xpert® MTB/RIF assay, and 57.7% and 99.3% for SM, respectively. 16 Le Palud et al concluded that as compared to culture, sensitivity and specificity values were 80.0% and 98.6% for the Xpert® MTB/RIF assay. 12 …”

Detecting active pulmonary tuberculosis with a breath test using nanomaterial-based sensors

“…One obvious advantage of breath analysis over sputum tests is the simplicity of obtaining the sample; this is in contrast to the difficulties in obtaining sputum both in children and HIV patients [5,6]. The lack of confounding by HIV is another clear advantage over the existing TB diagnostic tests, which exhibit up to 43% misclassification in HIV-TB co-infected persons [14].…”

“…In the present study, we used NAAT as a complementary diagnostic test to verify a true-negative result in subjects who were found to be negative with a sputum test [6], and were known to have relatively low sensitivity, yet a very high (,100%) specificity [4].…”

“…Acid-fast bacilli staining of sputum has a high false-negative rate (up to 50%) [4]. Nucleic acid amplification tests (NAATs), such as GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA, USA), are accurate but require a good infrastructure and the necessity to obtain a good quality sputum sample, which is often unobtainable in more than a third of HIV-infected persons [5,6].…”