Comparison of molecular and immunological methods for the rapid diagnosis of smear-negative tuberculosis

Abstract

Setting: The rapid diagnosis of pulmonary tuberculosis (TB) can be challenging if acid-fast bacilli are not detected by sputum smear microscopy.

Objective: To compare the results of the GeneXpert® MTB/RIF assay on a single sputum or bronchoalveolar lavage (BAL) specimen test with local immunodiagnosis from the site of disease using the T-SPOT®.TB assay on BAL (BAL T-SPOT).

Design: The Xpert and BAL T-SPOT tests were compared in 96 patients suspected of having sputum smear-negative pulmonary TB admitted to a referral centre in Germany.

Results: BAL T-SPOT identified 10 of 11 patients with pulmonary TB (including 3/4 patients with culture-confirmed TB) with a negative Xpert test. Using Xpert, the sensitivity, specificity and positive and negative likelihood ratios (LRs) were respectively 60.0%, 97.4%, 30.0% and 0.4% in culture-confirmed cases and 42.1%, 97.4%, 21.1% and 0.6% in all TB patients. In contrast, using BAL T-SPOT, the sensitivity, specificity and positive and negative LRs were respectively 80.0%, 62.6%, 2.1% and 0.3% in culture-confirmed cases and 89.4%, 62.6%, 2.4% and 0.2% in all TB patients.

Conclusion: In sputum smear-negative TB suspects, a positive Xpert result is strongly indicative of culture confirmation; however, a negative result is insufficient to rule out active TB. Where clinical suspicion of pulmonary TB persists despite a negative Xpert result, local immunodiagnosis using T-SPOT on BAL may increase diagnostic accuracy.