Abstract
BackgroundThe prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting.Methods28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.TB. We analyzed specimen types’ effect on these assays’ performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections.ResultsSputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB+/Xpert+ and 6/7 of AFB+/Xpert- cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB+ or Xpert+. However, T-SPOTMDC (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of Mycobacterium tuberculosis-specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT.TB assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB-/Xpert- patients.ConclusionsConcurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOTMDC and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB-/Xpert- patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers’ decisions regarding prevention and control of TB in a high burden setting.
Highlights
Tuberculosis (TB) caused by the pathogen Mycobacterium tuberculosis (M. tuberculosis, MTB) continues to pose a major threat to public health
Sputum and/ or BALF culture results were available for 7,528 patients, with 8.9% and 1.2% being positive for MTB and nontuberculous mycobacteria (NTM), respectively
When tuberculosis-specific antigens (TBAg)/PHA≥0.3 (Table 2) was used in conjunction with acid-fast bacilli (AFB) smear and/or Xpert, the specificity increased significantly. These results suggest that TBAg/PHA≥0.3 have some added values for pulmonary tuberculosis (PTB) diagnosis when combined with AFB smear and/or Xpert
Summary
Tuberculosis (TB) caused by the pathogen Mycobacterium tuberculosis (M. tuberculosis, MTB) continues to pose a major threat to public health. Typical TB diagnostic tools include acid-fast bacilli (AFB) smear microscopy, culture, Xpert MTB/RIF (Xpert), and interferon gamma (IFN-g) releasing assays (IGRAs) (Theron et al, 2012; Forbes et al, 2018). A positive culture of MTB from clinical samples is the gold standard for diagnosing active TB (ATB) infections. Xpert is a PCR-based test that simultaneously detects MTB and rifampin resistance (Forbes et al, 2018). Whether TBAg/ PHA ratios can be used to diagnose ATB in a real-world setting remains unclear. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting
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