Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area

Jia Fan, Hedong Zhang, Duc T. Nguyen, Christopher J. Lyon, Charles D. Mitchell, Zhen Zhao, Edward A. Graviss, Ye Hu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies. Methods: This study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Serum samples were trypsin-digested and immunoprecipitated for an Mtb-specific peptide of CFP-10 that was quantified by liquid chromatography-mass spectrometry for rapid and sensitive TB diagnosis. Results: Among the 1053 enrolled patients, 110 met all inclusion criteria; they included 60 tuberculosis cases (12 culture-negative TB), including 9 relapse TB cases, and 50 non-TB controls, including 15 cases with history of TB. Serum CFP-10 levels diagnosed 89.6% (77.3-96.5) and 66.7% (34.9-90.1) of culture-positive and culture-negative TB cases, respectively, and exhibited 88% (75.7-95.5) diagnostic specificity in all non-TB controls. Serum antigen detection and culture, respectively, identified 85% (73.4-92.9) and 80.0% (67.3-88.8) of all 60 TB cases. Conclusions: Quantitation of the Mtb virulence factor CFP-10 in serum samples of HIV-infected subjects diagnosed active TB cases with high sensitivity and specificity and detected cases missed by the gold standard of Mtb culture. These results suggest that serum CFP-10 quantitation holds great promise for the rapid diagnosis of suspected TB cases in patients who are HIV-infected.

Original languageEnglish (US)
Article number188
JournalBMC Medicine
Volume15
Issue number1
DOIs
StatePublished - Nov 1 2017

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HIV Antigens
Tuberculosis
Recurrence
Mycobacterium tuberculosis
Serum
HIV
Virulence Factors

Keywords

  • Blood test
  • CFP-10
  • Co-infection
  • Diagnosis
  • HIV
  • Immunoprecipitation
  • LC-MS/MS
  • Mycobacterium tuberculosis
  • Peptide biomarker

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area. / Fan, Jia; Zhang, Hedong; Nguyen, Duc T.; Lyon, Christopher J.; Mitchell, Charles D.; Zhao, Zhen; Graviss, Edward A.; Hu, Ye.

In: BMC Medicine, Vol. 15, No. 1, 188, 01.11.2017.

Research output: Contribution to journalArticle

Fan, Jia ; Zhang, Hedong ; Nguyen, Duc T. ; Lyon, Christopher J. ; Mitchell, Charles D. ; Zhao, Zhen ; Graviss, Edward A. ; Hu, Ye. / Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area. In: BMC Medicine. 2017 ; Vol. 15, No. 1.
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title = "Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area",
abstract = "Background: HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies. Methods: This study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Serum samples were trypsin-digested and immunoprecipitated for an Mtb-specific peptide of CFP-10 that was quantified by liquid chromatography-mass spectrometry for rapid and sensitive TB diagnosis. Results: Among the 1053 enrolled patients, 110 met all inclusion criteria; they included 60 tuberculosis cases (12 culture-negative TB), including 9 relapse TB cases, and 50 non-TB controls, including 15 cases with history of TB. Serum CFP-10 levels diagnosed 89.6{\%} (77.3-96.5) and 66.7{\%} (34.9-90.1) of culture-positive and culture-negative TB cases, respectively, and exhibited 88{\%} (75.7-95.5) diagnostic specificity in all non-TB controls. Serum antigen detection and culture, respectively, identified 85{\%} (73.4-92.9) and 80.0{\%} (67.3-88.8) of all 60 TB cases. Conclusions: Quantitation of the Mtb virulence factor CFP-10 in serum samples of HIV-infected subjects diagnosed active TB cases with high sensitivity and specificity and detected cases missed by the gold standard of Mtb culture. These results suggest that serum CFP-10 quantitation holds great promise for the rapid diagnosis of suspected TB cases in patients who are HIV-infected.",
keywords = "Blood test, CFP-10, Co-infection, Diagnosis, HIV, Immunoprecipitation, LC-MS/MS, Mycobacterium tuberculosis, Peptide biomarker",
author = "Jia Fan and Hedong Zhang and Nguyen, {Duc T.} and Lyon, {Christopher J.} and Mitchell, {Charles D.} and Zhen Zhao and Graviss, {Edward A.} and Ye Hu",
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T1 - Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area

AU - Fan, Jia

AU - Zhang, Hedong

AU - Nguyen, Duc T.

AU - Lyon, Christopher J.

AU - Mitchell, Charles D.

AU - Zhao, Zhen

AU - Graviss, Edward A.

AU - Hu, Ye

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Background: HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies. Methods: This study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Serum samples were trypsin-digested and immunoprecipitated for an Mtb-specific peptide of CFP-10 that was quantified by liquid chromatography-mass spectrometry for rapid and sensitive TB diagnosis. Results: Among the 1053 enrolled patients, 110 met all inclusion criteria; they included 60 tuberculosis cases (12 culture-negative TB), including 9 relapse TB cases, and 50 non-TB controls, including 15 cases with history of TB. Serum CFP-10 levels diagnosed 89.6% (77.3-96.5) and 66.7% (34.9-90.1) of culture-positive and culture-negative TB cases, respectively, and exhibited 88% (75.7-95.5) diagnostic specificity in all non-TB controls. Serum antigen detection and culture, respectively, identified 85% (73.4-92.9) and 80.0% (67.3-88.8) of all 60 TB cases. Conclusions: Quantitation of the Mtb virulence factor CFP-10 in serum samples of HIV-infected subjects diagnosed active TB cases with high sensitivity and specificity and detected cases missed by the gold standard of Mtb culture. These results suggest that serum CFP-10 quantitation holds great promise for the rapid diagnosis of suspected TB cases in patients who are HIV-infected.

AB - Background: HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies. Methods: This study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Serum samples were trypsin-digested and immunoprecipitated for an Mtb-specific peptide of CFP-10 that was quantified by liquid chromatography-mass spectrometry for rapid and sensitive TB diagnosis. Results: Among the 1053 enrolled patients, 110 met all inclusion criteria; they included 60 tuberculosis cases (12 culture-negative TB), including 9 relapse TB cases, and 50 non-TB controls, including 15 cases with history of TB. Serum CFP-10 levels diagnosed 89.6% (77.3-96.5) and 66.7% (34.9-90.1) of culture-positive and culture-negative TB cases, respectively, and exhibited 88% (75.7-95.5) diagnostic specificity in all non-TB controls. Serum antigen detection and culture, respectively, identified 85% (73.4-92.9) and 80.0% (67.3-88.8) of all 60 TB cases. Conclusions: Quantitation of the Mtb virulence factor CFP-10 in serum samples of HIV-infected subjects diagnosed active TB cases with high sensitivity and specificity and detected cases missed by the gold standard of Mtb culture. These results suggest that serum CFP-10 quantitation holds great promise for the rapid diagnosis of suspected TB cases in patients who are HIV-infected.

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KW - Co-infection

KW - Diagnosis

KW - HIV

KW - Immunoprecipitation

KW - LC-MS/MS

KW - Mycobacterium tuberculosis

KW - Peptide biomarker

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