BackgroundA crucial impediment to global tuberculosis control is the lack of an accurate, rapid diagnostic test for detection of patients with active TB. A new, rapid diagnostic method, (Cepheid) Xpert MTB/RIF Assay, is an automated sample preparation and real-time PCR instrument, which was shown to have good potential as an alternative to current reference standard sputum microscopy and culture.MethodsWe performed a clinical validation study on diagnostic accuracy of the Xpert MTB/RIF Assay in a TB and HIV endemic setting. Sputum samples from 292 consecutively enrolled adults from Mbeya, Tanzania, with suspected TB were subject to analysis by the Xpert MTB/RIF Assay. The diagnostic performance of Xpert MTB/RIF Assay was compared to standard sputum smear microscopy and culture. Confirmed Mycobacterium tuberculosis in a positive culture was used as a reference standard for TB diagnosis.ResultsXpert MTB/RIF Assay achieved 88.4% (95%CI = 78.4% to 94.9%) sensitivity among patients with a positive culture and 99% (95%CI = 94.7% to 100.0%) specificity in patients who had no TB. HIV status did not affect test performance in 172 HIV-infected patients (58.9% of all participants). Seven additional cases (9.1% of 77) were detected by Xpert MTB/RIF Assay among the group of patients with clinical TB who were culture negative. Within 45 sputum samples which grew non-tuberculous mycobacteria the assay's specificity was 97.8% (95%CI = 88.2% to 99.9%).ConclusionsThe Xpert MTB/RIF Assay is a highly sensitive, specific and rapid method for diagnosing TB which has potential to complement the current reference standard of TB diagnostics and increase its overall sensitivity. Its usefulness in detecting sputum smear and culture negative patients needs further study. Further evaluation in high burden TB and HIV areas under programmatic health care settings to ascertain applicability, cost-effectiveness, robustness and local acceptance are required.

Xpert was easy to perform and displayed similar diagnostic accuracy as culture methods in children with suspected tuberculosis. Rapid turnaround times should reduce treatment delay and improve patient outcome, although sensitivity remains suboptimal and access is dependent on local laboratory infrastructure.

We evaluated the use of the molecular bacterial load (MBL) assay, for measuring viable Mycobacterium tuberculosis in sputum, in comparison with solid agar and liquid culture. The MBL assay provides early information on the rate of decline in bacterial load and has technical advantages over culture in either form.

We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (LAM) into the urine, the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay, in children with suspected tuberculosis (TB) in a high TB/HIV-prevalence setting.In a prospective study, 132 children with suspected active TB were assigned to diagnostic subgroups. Urine samples were subjected to testing by both assays to ascertain sensitivity and specificity. Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation.18 (13.6%) children had culture-confirmed pulmonary TB. The assays' sensitivity was higher in HIVpositive versus HIV-negative children: 70% (95% confidence interval 35-93%) versus 13% (0-53%) for MTB-LAM-ELISA and 50% (19-81%) versus 0% (0-37%) for Determine TB-LAM. In 35 (27%) children with excluded active TB, both assays showed a specificity of 97.1% (85-100%). Proteinuria and low body mass index were independently associated with LAM positivity. In most patients, LAM excretion declined to zero during or at conclusion of antituberculous treatment.HIV/TB co-infected children might benefit from LAM-based tests to aid early TB diagnosis and subsequent positive impact on morbidity and mortality. Using LAM as a rule-in and treatment-monitoring tool may also show further potential. @ERSpublications Urine lipoarabinomannan assays show reasonable sensitivity in HIV+ but not HIV− TBinfected children

In this pilot study, we evaluated the Xpert® MTB/RIF assay in an active case-finding strategy, using two spot sputum samples collected within a 1-hour interval from household contacts of smear-positive TB index cases. Tuberculosis (TB) confirmed by culture served as the reference standard. Among 219 enrolled contacts, the yield of active TB was 2.3%. While the sensitivity of smear microscopy was 60% (95%CI 14.7-94.7), Xpert MTB/RIF achieved a sensitivity of 100% (95%CI 47.81-100.0). All culture-confirmed cases tested positive by Xpert MTB/RIF on the first submitted sample, suggesting that the evaluation of only one sample could be sufficient for TB diagnosis in this context.