Xi Liu1, Yuanli Chen2, Hui Ouyang3, Jian Liu3, Xiaoqing Luo3, Yayi Huang3, Yan Chen4, Jinmin Ma4, Jinyu Xia5, Li Ding6. 1. Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China; Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China. 2. Department of Hospital Infection Control, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. 3. Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. 4. BGI PathoGenesis Pharmaceutical Technology, BGI-Shenzhen, Shenzhen, China. 5. Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. Electronic address: xiajinyu@mail.sysu.edu.cn. 6. Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. Electronic address: dingli@mail.sysu.edu.cn.
Abstract
BACKGROUND: Metagenomic next-generation sequencing (mNGS) is an effective diagnostic method for infectious diseases, however, its clinical utility for tuberculosis (TB) diagnosis remains to be demonstrated. METHODS: A total of 322 bronchoalveolar lavage fluid (BALF) samples were collected from 311 suspected and confirmed pulmonary TB patients and tested by mNGS, acid-fast bacillus (AFB) smear by microscopy, Xpert® MTB/RIF (Xpert), mycobacterium culture and bacterial/fungal culture. Diagnostic performance of mNGS was compared with conventional methods for detection of Mycobacterium tuberculosis complex (MTBC) and other pathogens in BALF. Underlying factors associated with positive detection in pulmonary TB patients were investigated. RESULTS: mNGS, Xpert and culture presented a high proportion of complete matching for MTBC detection (244/322, 75.8%). In pulmonary TB patients pre-treatment the sensitivity of MTBC detection by mNGS, Xpert, culture and smear was 59.9% (85/142), 69.0% (98/142), 59.9% (85/142) and 24.6% (35/142), respectively, and 79.6% overall; MTBC was detected by mNGS in 33.2% (5/34) Xpert and culture negative samples. Positive MTBC detection by mNGS was affected by Vitamin D, erythrocyte sedimentation rate, TB initial treatment/retreatment, and cavity in chest imaging (χ2 = 37.42, P < 0.001), but not by prior anti-TB therapy within 3 months. mNGS was able to detect new potential pathogens in 8.7% (28/322) of samples. CONCLUSIONS: Combining mNGS with conventional detection methods could increase the detection rate for MTBC. Additionally, mNGS could identify pathogens in a non-targeted approach for better diagnosis of coinfection.
BACKGROUND: Metagenomic next-generation sequencing (mNGS) is an effective diagnostic method for infectious diseases, however, its clinical utility for tuberculosis (TB) diagnosis remains to be demonstrated. METHODS: A total of 322 bronchoalveolar lavage fluid (BALF) samples were collected from 311 suspected and confirmed pulmonary TB patients and tested by mNGS, acid-fast bacillus (AFB) smear by microscopy, Xpert® MTB/RIF (Xpert), mycobacterium culture and bacterial/fungal culture. Diagnostic performance of mNGS was compared with conventional methods for detection of Mycobacterium tuberculosis complex (MTBC) and other pathogens in BALF. Underlying factors associated with positive detection in pulmonary TB patients were investigated. RESULTS:mNGS, Xpert and culture presented a high proportion of complete matching for MTBC detection (244/322, 75.8%). In pulmonary TB patients pre-treatment the sensitivity of MTBC detection by mNGS, Xpert, culture and smear was 59.9% (85/142), 69.0% (98/142), 59.9% (85/142) and 24.6% (35/142), respectively, and 79.6% overall; MTBC was detected by mNGS in 33.2% (5/34) Xpert and culture negative samples. Positive MTBC detection by mNGS was affected by Vitamin D, erythrocyte sedimentation rate, TB initial treatment/retreatment, and cavity in chest imaging (χ2 = 37.42, P < 0.001), but not by prior anti-TB therapy within 3 months. mNGS was able to detect new potential pathogens in 8.7% (28/322) of samples. CONCLUSIONS: Combining mNGS with conventional detection methods could increase the detection rate for MTBC. Additionally, mNGS could identify pathogens in a non-targeted approach for better diagnosis of coinfection.