Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples

Zhou, Xian; Wu, Honglong; Ruan, Qingwei; Jiang, Ning; Chen, Xinchang; Shen, Yaojie; Zhu, Yimin; Ye, Ying; Qian, Yue; Wang, Xuyang; Ai, Jingwen; Zhang, Wenhong

doi:10.3389/fcimb.2019.00351

Cited by 102 publications

(109 citation statements)

References 24 publications

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“…As described before [22,23], low-quality and short (length < 35 bp) reads were removed. Then the filtered sequences were mapped to human reference database including hg38 and Yanhuang genome sequence using Burrows-Wheeler Alignment (Version: 0.7.10).…”

Section: Sample Sequencing and Data Analysismentioning

confidence: 99%

Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection

et al. 2020

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Background: Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections. Methods: We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded. Results: mNGS reported a 90.00% (9/10) sensitivity in culture-positive patients without empirical treatment and 66.67% (6/9) in empirically-treated patients. Detected an extra of 48 bacteria and fungi in culture-negative patients, mNGS provided a higher detection rate compared to culture in patients with (34.45% vs. 7.56%, McNemar test, p < 0.0083) or without empirical therapy (50.00% vs. 25.00%, McNemar test, p > 0.0083). Compared to conventional methods, positive percent agreement and negative percent agreement was 75.00% and 69.11% separately. mNGS detection rate was significantly higher in patients with cerebrospinal fluid (CSF) WBC > 300 * 10 6 /L, CSF protein > 500 mg/L or glucose ratio ≤ 0.3. mNGS sequencing read is correlated with CSF WBC, glucose ratio levels and clinical disease progression. Conclusion: mNGS showed a satisfying diagnostic performance in CNS infections and had an overall superior detection rate to culture. mNGS may held diagnostic advantages especially in empirically treated patients. CSF laboratory results were statistically relevant to mNGS detection rate, and mNGS could dynamically monitor disease progression.

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Section: Sample Sequencing and Data Analysismentioning

confidence: 99%

Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection

et al. 2020

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“…After searching relevant databases using our search strategy, we identified 1097 candidate articles. Of these articles, four, including two retrospective and two prospective, studies met the inclusion criteria [15][16][17]23] (Fig 1). The kappa index of agreement for the selection of studies and data extraction was 0.665 (95% confidence interval [CI]: 0.355-0.975) between the two investigators.…”

Section: Characteristics Of the Studiesmentioning

confidence: 99%

Metagenomic next generation sequencing for the diagnosis of tuberculosis meningitis: A systematic review and meta-analysis

Yu¹,

Zhao²,

Shen³

et al. 2020

PLoS ONE

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Background Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis and its early diagnosis is very difficult leading to present with severe disability or die. The current study aimed to assess the accuracy of metagenomic next generation sequencing (mNGS) for TBM, and to identify a new test for the early diagnosis of TBM. Methods We searched for articles published in Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data up to June 30, 2020 for studies that assessed the efficacy of mNGS for the diagnosis of TBM. Then, the accuracy between mNGS and a composite reference standard (CRS) in these articles was compared using the meta-analysis approach. Results Four independent studies with 342 samples comparing mNGS and a CRS were included in this study. The sensitivity of mNGS for TBM diagnosis ranged from 27% to 84%. The combined sensitivity of mNGS was 61%, and the I2 value was 92%. Moreover, the specificity of mNGS for TBM diagnosis ranged from 96% to 100%. The combined specificity of mNGS was 98%, and the I2 value was 74%. The heterogeneity between studies in terms of sensitivity and specificity was significant. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for TBM was 0.98. Conclusions The sensitivity of mNGS for TBM diagnosis was moderate. Furthermore, the specificity was extremely high, and the AUC of the SROC indicated a very good diagnostic efficacy. mNGS could be used as an early diagnostic method for TBM, however, the results should be treated with caution for the heterogeneity between studies was extremely significant. Systematic review registration INPLASY202070100.

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“…Of note, mNGS can assist in identifying bloodstream infection in patients with severe pneumonia. Mounting evidence has recently demonstrated that bloodstream infection is an important predictor of worsening prognosis in patients with severe pneumonia [19,20]. Therefore, a high detection frequency of complications resulting from bloodstream infection in patients with severe pneumonia warrants attention.…”

Section: Discussionmentioning

confidence: 99%

“…mNGS testing of the BALF and blood samples was performed and analysed by BGI-Shenzhen as previously reported [17][18][19]. BALF and blood samples were obtained on the same day and immediately used for the mNGS detection.…”

Section: Metagenomic Next-generation Sequencingmentioning

confidence: 99%

The clinical significance of simultaneous detection of pathogens from bronchoalveolar lavage fluid and blood samples by metagenomic next-generation sequencing in patients with severe pneumonia

Chen

Zhao

Shang

et al. 2021

Journal of Medical Microbiology

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Introduction. Bloodstream infection is a common complication in patients with severe pneumonia and is regarded as an independent risk factor for prediction of poor outcome. Metagenomic next-generation sequencing (mNGS) has been widely applied for pathogen determination of various clinical specimens from patients with infectious diseases. However, the clinical significance of and necessity for simultaneous pathogen detection of both blood samples and bronchoalveolar lavage fluid (BALF) by mNGS in patients with severe pneumonia remains unclear. Hypothesis/Gap Statement. Simultaneous detection of pathogens from both BALF and blood samples in patients with severe pneumonia helps to determine the complication of the bloodstream infection. Aims. This study aimed to elucidate the clinical significance and necessity of pathogen detection simultaneously in both blood samples and BALF samples with the application of mNGS in patients with severe pneumonia. Methods. In this study, 20 patients with severe pneumonia were enrolled and the potential pathogens in both BALF and blood samples were detected simultaneously by conventional microbial examination and mNGS tests. Moreover, multiple consecutive microbial detections were undertaken to investigate the dynamic variation of pathogens during the course of disease progression in two of the 20 patients. Results. In 85 % (17/20) of the patients with severe pneumonia, various pathogens were determined positively in the BALF by mNGS, including 10 cases with bacterial infection, five cases with viral infection and two cases with fungal infection. By contrast, pathogens in 50 % (10/20) of cases could be detected positively in the BALF by conventional microbial tests. Among 17 severe pneumonia patients with mNGS-positive BALF, pathogens were also identified in 10 cases with mNGS-positive blood samples. By contrast, only one patient complicated with a bloodstream infection could be found by conventional bacterial culture. Moreover, the pathogens from BALF were highly consistent with that from blood samples detected by mNGS in the early stage of the disease. With disease progression and after recurrent antibiotic treatment, significant dynamic changes of the microbial species from the BALF and blood samples could be clearly found by mNGS. Conclusions. This study emphasizes the utility of mNGS in the rapid simultaneous detection of pathogens from both BALF and blood samples in patients with severe pneumonia, and could allow determination of bloodstream infection and guide clinicians regarding antimicrobial treatments.

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Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples

Cited by 102 publications

References 24 publications

Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection

Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection

Metagenomic next generation sequencing for the diagnosis of tuberculosis meningitis: A systematic review and meta-analysis

The clinical significance of simultaneous detection of pathogens from bronchoalveolar lavage fluid and blood samples by metagenomic next-generation sequencing in patients with severe pneumonia

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