Performance of Nucleic Acid Amplification Tests in Patients with Presumptive Pulmonary Tuberculosis in Taiwan

Wei-Chang Huang; Chih-Bin Lin; Shun-Tien Chien; Jann-Yuan Wang; Chou-Jui Lin; Jia-Yih Feng; Chih-Hsin Lee; Chin-Chung Shu; Ming-Chih Yu; Jen-Jyh Lee; Chen-Yuan Chiang

doi:10.1007/s40121-022-00610-2

Performance of Nucleic Acid Amplification Tests in Patients with Presumptive Pulmonary Tuberculosis in Taiwan

Infect Dis Ther. 2022 Apr;11(2):871-885. doi: 10.1007/s40121-022-00610-2. Epub 2022 Mar 7.

Authors

Wei-Chang Huang^#^{1

2

3

4

5

6}, Chih-Bin Lin^#^{7

8}, Shun-Tien Chien^#⁹, Jann-Yuan Wang^{10

11}, Chou-Jui Lin¹², Jia-Yih Feng^{13

14

15}, Chih-Hsin Lee^{16

17}, Chin-Chung Shu^{10

11}, Ming-Chih Yu^{16

18}, Jen-Jyh Lee^{7

8}, Chen-Yuan Chiang^{19

20

21}

Affiliations

¹ Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, 407, Taiwan.
² Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 402, Taiwan.
³ Department of Translational Medicine, National Chung Hsing University, Taichung, 402, Taiwan.
⁴ School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan.
⁵ Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, 407, Taiwan.
⁶ Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, 350, Taiwan.
⁷ Division of Chest Medicine, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan.
⁸ School of Medicine, Tzu Chi University, Hualien, 970, Taiwan.
⁹ Chest Hospital, Ministry of Health and Welfare, Tainan, 701, Taiwan.
¹⁰ Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
¹¹ School of Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
¹² Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 330, Taiwan.
¹³ Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
¹⁴ School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan.
¹⁵ Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan.
¹⁶ Division of Pulmonary Medicine & Pulmonary Research Center, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Xing-Long Road, Section 3, Taipei, 116, Taiwan.
¹⁷ Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
¹⁸ School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
¹⁹ Division of Pulmonary Medicine & Pulmonary Research Center, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Xing-Long Road, Section 3, Taipei, 116, Taiwan. cychiang@theunion.org.
²⁰ Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. cychiang@theunion.org.
²¹ International Union Against Tuberculosis and Lung Disease, Paris, France. cychiang@theunion.org.

^# Contributed equally.

Abstract

Introduction: Several nucleic acid amplification tests (NAATs) for detection of Mycobacterium tuberculosis (TB) complex (MTBC) are available in Taiwan; however, their performances may differ and have not been extensively evaluated. Therefore, we aimed to explore the accuracy of NAATs overall followed by comparison between platforms commonly used in Taiwan.

Methods: This study enrolled presumptive pulmonary TB patients with NAATs throughout Taiwan. The diagnostic performance of smear microscopy and NAATs was assessed using sputum culture as a reference standard. To investigate the performance of NAATs in excluding non-tuberculous mycobacteria (NTM), we quantified the false-positive proportion of NAATs in patients infected with NTM.

Results: Of the 4126 enrollees, 860 (20.8%) had positive NAATs. The sensitivity and specificity of NAATs were 83.2% and 96.7%, respectively, compared to 81.5% and 55.3% for smear. There was no significant difference in sensitivity between the NAATs and smear; however, the specificity of smear was significantly lower than that of the NAATs [difference 41.4%, 95% confidence interval (CI) 39.6-43.2%]. There was no significant difference in sensitivity among Roche Cobas Amplicor Mycobacterium tuberculosis assay (Amplicor), Xpert MTB/RIF assay (Xpert) and in-house polymerase chain reaction (in-house PCR) (82.2% versus 83.8% versus 82.4%); however, in-house PCR was significantly less specific than Amplicor (difference 5.3%, 95% CI 2.4-8.2%) and Xpert (difference 5.8%, 95% CI 3.1-8.5%). The sensitivity of NAATs among smear-negative cases was 33.1% (95% CI 26.0-40.3%). In-house PCR had a significantly higher false-positive rate among specimens that were culture positive for NTM than Amplicor (7.7% versus 0.3%; difference 7.4%, 95% CI 3.4-11.5%) and Xpert (7.7% versus 0.7%; difference 7.0%, 95% CI 2.9-11.0%).

Conclusion: The NAATs overall had a relatively high sensitivity and specificity in detecting MTBC while Amplicor and Xpert performed better than in-house PCR in excluding NTM. Our findings will be useful for the development of national policy.

Keywords: In-house PCR; Nucleic acid amplification; Performance; Roche Cobas Amplicor Mycobacterium tuberculosis assay; Xpert MTB/RIF assay.

Grants and funding

MOST 108-2314-B-038-122/Ministry of Science and Technology, Taiwan