The Health-System Benefits and Cost-effectiveness of Using Mycobacterium Tuberculosis Direct Nucleic Acid Amplification Testing to Diagnose Tuberculosis Disease in the United States

Improvements in diagnosis of tuberculosis disease are needed. Sputum-smear microscopy for acid-fast-bacilli (AFB) is simple and inexpensive to perform but generally detects less than half of patients with culture-confirmed pulmonary Mycobacterium tuberculosis complex disease (culture-positivity) [1, 2] and has a poor positive predictive value (PPV) in persons with human immunodeficiency virus (HIV) infection [3, 4]. While culture is the gold standard for active tuberculosis diagnosis, it takes 2–8 weeks for results [1]. Nucleic acid amplification testing for M. tuberculosis can provide information within 24–48 hours. A meta-analysis of M. tuberculosis direct nucleic acid amplification testing (MTD, Gen-Probe, San Diego, California) studies found sensitivity of 97% and specificity of 96% among smear-positive respiratory specimens, and sensitivity of 76% and specificity of 97% among smear-negative specimens [5]. The US Food and Drug Administration (FDA) approved the MTD in 1995 for smear-positive specimens and an enhanced MTD in 1999 for both smear-positive and smear-negative specimens. The Centers for Disease Control and Prevention (CDC) recommended in 1996 and 2000 that nucleic acid amplification testing be performed on at least one (preferably the first) respiratory specimen if smear-positive, and beginning in 2009 on smear-negative specimens from patients for whom the test result would alter tuberculosis case management [6]. Despite these recommendations, the request for MTD by individual providers, hospitals, and laboratories determines its use, which is not universal. Moreover, there are limited US data demonstrating the cost-effectiveness of the MTD, which might influence its use. D. W. Dowdy evaluated the MTD in smear-positive patients having 31.4% tuberculosis prevalence at a US urban hospital and found it not cost-effective for early tuberculosis exclusion in that setting [7]. The purpose of this study is to evaluate the use, effectiveness, health-system benefits, and cost-effectiveness of MTD in a retrospective cohort of patients reported to have suspected pulmonary tuberculosis in 2008–2010 from Georgia, Hawaii, Maryland, and Massachusetts. Study results will help guide future decisions about efficient MTD and provide a baseline for newer molecular tuberculosis disease diagnostics, such as Xpert INH/RIF (Cepheid, Sunnyvale, California).