Clinical evaluation of a blood assay to diagnose paucibacillary tuberculosis via bacterial antigens

Chang Liu, Christopher J. Lyon, Yang Bu, Zaian Deng, Elisabetta Walters, Yan Li, Liqun Zhang, Anneke C. Hesseling, Edward A. Graviss, Ye Hu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND: The diagnosis of active tuberculosis (TB) cases primarily relies on methods that detect Mycobacterium tuberculosis (Mtb) bacilli or their DNA in patient samples (e.g., mycobacterial culture and Xpert MTB/RIF assays), but these tests have low clinical sensitivity for patients with paucibacillary TB disease. Our goal was to evaluate the clinical performance of a newly developed assay that can rapidly diagnose active TB cases by direct detection of Mtb-derived antigens in patients’ blood samples. METHODS: Nanoparticle (NanoDisk)-enriched peptides derived from the Mtb virulence factors CFP-10 (10-kDa culture factor protein) and ESAT-6 (6-kDa early secretory antigenic target) were analyzed by high-throughput mass spectrometry (MS). Serum from 294 prospectively enrolled Chinese adults were analyzed with this NanoDisk-MS method to evaluate the performance of direct serum Mtbantigen measurement as a means for rapid diagnosis of active TB cases. RESULTS: NanoDisk-MS diagnosed 174 (88.3%) of the study’s TB cases, with 95.8% clinical specificity, and with 91.6% and 85.3% clinical sensitivity for culture-positive and culture-negative TB cases, respectively. NanoDisk-MS also exhibited 88% clinical sensitivity for pulmonary and 90% for extrapulmonary TB, exceeding the diagnostic performance of mycobacterial culture for these cases. CONCLUSIONS: Direct detection and quantification of serum Mtb antigens by NanoDisk-MS can rapidly and accurately diagnose active TB in adults, independent of disease site or culture status, and outperform Mycobacterium-based TB diagnostics.

Original languageEnglish (US)
Pages (from-to)791-800
Number of pages10
JournalClinical Chemistry
Volume64
Issue number5
DOIs
StatePublished - May 1 2018

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Bacterial Antigens
Mass spectrometry
Assays
Tuberculosis
Blood
Mass Spectrometry
Mycobacterium tuberculosis
Virulence Factors
Bacilli
Serum
Throughput
Nanoparticles
Antigens
Peptides
Bacillus
DNA
Proteins
Lung

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Clinical evaluation of a blood assay to diagnose paucibacillary tuberculosis via bacterial antigens. / Liu, Chang; Lyon, Christopher J.; Bu, Yang; Deng, Zaian; Walters, Elisabetta; Li, Yan; Zhang, Liqun; Hesseling, Anneke C.; Graviss, Edward A.; Hu, Ye.

In: Clinical Chemistry, Vol. 64, No. 5, 01.05.2018, p. 791-800.

Research output: Contribution to journalArticle

Liu, C, Lyon, CJ, Bu, Y, Deng, Z, Walters, E, Li, Y, Zhang, L, Hesseling, AC, Graviss, EA & Hu, Y 2018, 'Clinical evaluation of a blood assay to diagnose paucibacillary tuberculosis via bacterial antigens', Clinical Chemistry, vol. 64, no. 5, pp. 791-800. https://doi.org/10.1373/clinchem.2017.273698
Liu, Chang ; Lyon, Christopher J. ; Bu, Yang ; Deng, Zaian ; Walters, Elisabetta ; Li, Yan ; Zhang, Liqun ; Hesseling, Anneke C. ; Graviss, Edward A. ; Hu, Ye. / Clinical evaluation of a blood assay to diagnose paucibacillary tuberculosis via bacterial antigens. In: Clinical Chemistry. 2018 ; Vol. 64, No. 5. pp. 791-800.
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AU - Deng, Zaian

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AU - Zhang, Liqun

AU - Hesseling, Anneke C.

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N2 - BACKGROUND: The diagnosis of active tuberculosis (TB) cases primarily relies on methods that detect Mycobacterium tuberculosis (Mtb) bacilli or their DNA in patient samples (e.g., mycobacterial culture and Xpert MTB/RIF assays), but these tests have low clinical sensitivity for patients with paucibacillary TB disease. Our goal was to evaluate the clinical performance of a newly developed assay that can rapidly diagnose active TB cases by direct detection of Mtb-derived antigens in patients’ blood samples. METHODS: Nanoparticle (NanoDisk)-enriched peptides derived from the Mtb virulence factors CFP-10 (10-kDa culture factor protein) and ESAT-6 (6-kDa early secretory antigenic target) were analyzed by high-throughput mass spectrometry (MS). Serum from 294 prospectively enrolled Chinese adults were analyzed with this NanoDisk-MS method to evaluate the performance of direct serum Mtbantigen measurement as a means for rapid diagnosis of active TB cases. RESULTS: NanoDisk-MS diagnosed 174 (88.3%) of the study’s TB cases, with 95.8% clinical specificity, and with 91.6% and 85.3% clinical sensitivity for culture-positive and culture-negative TB cases, respectively. NanoDisk-MS also exhibited 88% clinical sensitivity for pulmonary and 90% for extrapulmonary TB, exceeding the diagnostic performance of mycobacterial culture for these cases. CONCLUSIONS: Direct detection and quantification of serum Mtb antigens by NanoDisk-MS can rapidly and accurately diagnose active TB in adults, independent of disease site or culture status, and outperform Mycobacterium-based TB diagnostics.

AB - BACKGROUND: The diagnosis of active tuberculosis (TB) cases primarily relies on methods that detect Mycobacterium tuberculosis (Mtb) bacilli or their DNA in patient samples (e.g., mycobacterial culture and Xpert MTB/RIF assays), but these tests have low clinical sensitivity for patients with paucibacillary TB disease. Our goal was to evaluate the clinical performance of a newly developed assay that can rapidly diagnose active TB cases by direct detection of Mtb-derived antigens in patients’ blood samples. METHODS: Nanoparticle (NanoDisk)-enriched peptides derived from the Mtb virulence factors CFP-10 (10-kDa culture factor protein) and ESAT-6 (6-kDa early secretory antigenic target) were analyzed by high-throughput mass spectrometry (MS). Serum from 294 prospectively enrolled Chinese adults were analyzed with this NanoDisk-MS method to evaluate the performance of direct serum Mtbantigen measurement as a means for rapid diagnosis of active TB cases. RESULTS: NanoDisk-MS diagnosed 174 (88.3%) of the study’s TB cases, with 95.8% clinical specificity, and with 91.6% and 85.3% clinical sensitivity for culture-positive and culture-negative TB cases, respectively. NanoDisk-MS also exhibited 88% clinical sensitivity for pulmonary and 90% for extrapulmonary TB, exceeding the diagnostic performance of mycobacterial culture for these cases. CONCLUSIONS: Direct detection and quantification of serum Mtb antigens by NanoDisk-MS can rapidly and accurately diagnose active TB in adults, independent of disease site or culture status, and outperform Mycobacterium-based TB diagnostics.

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