A Nucleic Acid Amplification Assay in the Diagnosis and Management of Tuberculosis in a Low-incidence Area

Background: Smear is insensitive and culture is slow, but both methods are essential in tuberculosis (TB) diagnostics. The nucleic acid amplification (NAA) assay is sensitive and rapid, but its role as an additive test in the diagnosis of TB has remained undefined. Aims: The objective was to estimate the specimenand patient-based performance of the NAA assay in detecting Mycobacterium tuberculosis (M. tuberculosis) complex from sputum specimens, and to assess its usefulness in monitoring treatment response of pulmonary TB patients. In addition, the cost-effectiveness of the NAA assay and its impact on clinical TB practice was evaluated. Subjects and methods: The study population, altogether 386 subjects and 34 controls, included 327 patients with suspicion of TB, 44 patients with past TB and 15 patients receiving chemotherapy for TB. They were tested by smear, culture and NAA tests. Both laboratory and patient records were reviewed retrospectively. Additionally, a decision tree model was used to evaluate the cost-effectiveness of the NAA assay in diagnosing pulmonary TB. Results: The overall sensitivity of the NAA assay in detecting M. tuberculosis complex from sputum specimens was 83 % compared to culture; the specificity, PPV and NPV were 99 %, 97 % and 95 %, respectively. In patient-based evaluation the sensitivity increased to 90 % when three specimens per patient were tested. Further, the sensitivity was 100 % for smearpositive and 75 % for smear-negative patients. No false positive NAA results were detected in patients who had residual lung lesions due to previous TB. NAA test results proved inconsistent in TB patients during chemotherapy and no clinically significant difference between the two different types of NAA assay was found. Routine testing of all TB suspects by the NAA assay was not cost-effective, whereas testing of smear-positive patients was less costly and resulted in more appropriate treatment decisions. However, in clinical evaluation the median NAA test result delay was one week, and NAA testing was of value in only part of the smear-positive cases. Conclusions: The NAA assay is recommended for use in smear-positive patients with TB suspicion, particularly when distinguishing TB from nontuberculous mycobacteria (NTM) or other disease is difficult. It may also be applied to smear-negative patients with high clinical suspicion of TB, and testing of multiple specimens is recommended. A positive NAA test result is indicative of active TB, but in smear-negative patients TB cannot be excluded by negative NAA results. Moreover, qualitative NAA tests were not found useful in monitoring response to TB treatment. Finally, centralizing of NAA testing is recommended in a lowincidence area.