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BMC Medicine
Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Research article

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

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

Published in: BMC Medicine | Issue 1/2017

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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.
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Literature
1.
WHO. Global tuberculosis control: WHO report 2014 (WHO/HTM/TB/2014.08). Geneva: World Health Organization; 2014.
2.
Shedden K, Xie XT, Chandaroy P, Chang YT, Rosania GR. Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res. 2003;63(15):4331–7.PubMed
3.
Peter JG, Theron G, Pooran A, Thomas J, Pascoe M, Dheda K. Comparison of two methods for acquisition of sputum samples for diagnosis of suspected tuberculosis in smear-negative or sputum-scarce people: a randomised controlled trial. Lancet Respir Med. 2013;1(6):471–8.CrossRefPubMedPubMedCentral
4.
WHO. Improving the diagnosis and treatment of smear-negative pulmonary and extra-pulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource-constrained settings (WHO/HTM/HIV/2007.01). Geneva: World Health Organization; 2007.
5.
Bates M, Mudenda V, Shibemba A, Kaluwaji J, Tembo J, Kabwe M, Chimoga C, Chilukutu L, Chilufya M, Kapata N, et al. Burden of tuberculosis at post mortem in inpatients at a tertiary referral centre in sub-Saharan Africa: a prospective descriptive autopsy study. Lancet Infect Dis. 2015;15(5):544–51.CrossRefPubMed
6.
Cox JA, Lukande RL, Lucas S, Nelson AM. Autopsy causes of death in HIV-positive individuals in sub-Saharan Africa and correlation with clinical diagnoses. AIDS Rev. 2010;12(4):183–94.PubMed
7.
Vernon A, Burman W, Benator D, Khan A, Bozeman L. Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Tuberculosis Trials Consortium. Lancet. 1999;353(9167):1843–7.CrossRefPubMed
8.
Glynn JR, Murray J, Bester A, Nelson G, Shearer S, Sonnenberg P. High rates of recurrence in HIV-infected and HIV-uninfected patients with tuberculosis. J Infect Dis. 2010;201(5):704–11.CrossRefPubMed
9.
10.
11.
WHO. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva: World Health Organization; 2014.
12.
Simossis VA, Heringa J. The PRALINE online server: optimising progressive multiple alignment on the web. Comput Biol Chem. 2003;27(4–5):511–9.CrossRefPubMed
13.
van Ingen J, de Zwaan R, Dekhuijzen R, Boeree M, van Soolingen D. Region of difference 1 in nontuberculous Mycobacterium species adds a phylogenetic and taxonomical character. J Bacteriol. 2009;191(18):5865–7.CrossRefPubMedPubMedCentral
14.
Wu HJ, Li Y, Fan J, Deng Z, Hu Z, Liu X, Graviss EA, Ferrari M, Ma X, Hu Y. Antibody-free detection of Mycobacterium tuberculosis antigen using customized nanotraps. Anal Chem. 2014;86(4):1988–96.CrossRefPubMedPubMedCentral
15.
Liu C, Zhao Z, Fan J, Lyon CJ, Wu HJ, Nedelkov D, Zelazny AM, Olivier KN, Cazares LH, Holland SM, et al. Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring. Proc Natl Acad Sci U S A. 2017;114(15):3969–74.CrossRefPubMedPubMedCentral
16.
Sørensen AL, Nagai S, Houen G, Andersen P, Andersen AB. Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis. Infect Immun. 1995;63(5):1710–7.PubMedPubMedCentral
17.
Berthet F-X, Rasmussen PB, Rosenkrands I, Andersen P, Gicquel B. A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10). Microbiology. 1998;144(11):3195–203.
18.
Denkinger CM, Pai M, Patel M, Menzies D. Gamma interferon release assay for monitoring of treatment response for active tuberculosis: an explosion in the spaghetti factory. J Clin Microbiol. 2013;51(2):607–10.CrossRefPubMedPubMedCentral
19.
Brusasca PN, Colangeli R, Lyashchenko KP, Zhao X, Vogelstein M, Spencer JS, McMurray DN, Gennaro ML. Immunological characterization of antigens encoded by the RD1 region of the Mycobacterium tuberculosis genome. Scand J Immunol. 2001;54(5):448–52.CrossRefPubMed
20.
Feng TT, Shou CM, Shen L, Qian Y, Wu ZG, Fan J, Zhang YZ, Tang YW, Wu NP, Lu HZ, et al. Novel monoclonal antibodies to ESAT-6 and CFP-10 antigens for ELISA-based diagnosis of pleural tuberculosis. Int J Tuberc Lung Dis. 2011;15(6):804–10.CrossRefPubMed
21.
Grimes CZ, Teeter LD, Hwang LY, Graviss EA. Epidemiologic characterization of culture positive Mycobacterium tuberculosis patients by katG-gyrA principal genetic grouping. J Mol Diagn. 2009;11(5):472–81.CrossRefPubMedPubMedCentral
22.
Prevention CfDCa. Core curriculum on tuberculosis: what the clinician should know. Chapter 6: Treatment of tuberculosis disease. Atlanta: CDC; 2016.
23.
Centers for Disease Control. Patients with recurrent tuberculosis. MMWR Morb Mortal Wkly Rep. 1982;30:645–7.
24.
Eurosurveillance Editorial Team. WHO revised definitions and reporting framework for tuberculosis. Euro Surveill. 2013;18:20455.
25.
van Cleeff MR, Kivihya-Ndugga L, Githui W, Nganga L, Odhiambo J, Klatser PR. A comprehensive study of the efficiency of the routine pulmonary tuberculosis diagnostic process in Nairobi. Int J Tuberc Lung Dis. 2003;7(2):186–9.PubMed
26.
27.
El Sahly HM, Wright JA, Soini H, Bui TT, Williams-Bouyer N, Escalante P, Musser JM, Graviss EA. Recurrent tuberculosis in Houston, Texas: a population-based study. Int J Tuberc Lung Dis. 2004;8(3):333–40.PubMed
28.
CDC. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Centers for Disease Control and Prevention. 2013.
29.
Friedrich SO, Rachow A, Saathoff E, Singh K, Mangu CD, Dawson R, Phillips PP, Venter A, Bateson A, Boehme CC, et al. Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment. Lancet Respir Med. 2013;1(6):462–70.CrossRefPubMed
30.
Fitzwater SP, Caviedes L, Gilman RH, Coronel J, LaChira D, Salazar C, Saravia JC, Reddy K, Friedland JS, Moore DA. Prolonged infectiousness of tuberculosis patients in a directly observed therapy short-course program with standardized therapy. Clin Infect Dis. 2010;51(4):371–8.CrossRefPubMedPubMedCentral
31.
Ko Y, Shin JH, Lee HK, Lee YS, Lee SY, Park SY, Mo EK, Kim C, Park YB. Duration of pulmonary tuberculosis infectiousness under adequate therapy, as assessed using induced sputum samples. Tuberc Respir Dis (Seoul). 2017;80(1):27–34.CrossRef
32.
Theron G, Peter J, van Zyl-Smit R, Mishra H, Streicher E, Murray S, Dawson R, Whitelaw A, Hoelscher M, Sharma S, et al. Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting. Am J Respir Crit Care Med. 2011;184(1):132–40.CrossRefPubMed
33.
Rachow A, Zumla A, Heinrich N, Rojas-Ponce G, Mtafya B, Reither K, Ntinginya EN, O'Grady J, Huggett J, Dheda K, et al. Rapid and accurate detection of Mycobacterium tuberculosis in sputum samples by Cepheid Xpert MTB/RIF assay—a clinical validation study. PLoS One. 2011;6(6):e20458.CrossRefPubMedPubMedCentral
34.
WHO. Policy update: Xpert MTB/RIF assay for the diagnosis of pulmonary and extrapulmonary TB in adults and children. Geneva: World Health Organization; 2013.
35.
Denkinger CM, Schumacher SG, Boehme CC, Dendukuri N, Pai M, Steingart KR. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2014;44(2):435–46.CrossRefPubMed
36.
Maynard-Smith L, Larke N, Peters JA, Lawn SD. Diagnostic accuracy of the Xpert MTB/RIF assay for extrapulmonary and pulmonary tuberculosis when testing non-respiratory samples: a systematic review. BMC Infect Dis. 2014;14:709.CrossRefPubMedPubMedCentral
37.
Theron G, Peter J, Calligaro G, Meldau R, Hanrahan C, Khalfey H, Matinyenya B, Muchinga T, Smith L, Pandie S, et al. Determinants of PCR performance (Xpert MTB/RIF), including bacterial load and inhibition, for TB diagnosis using specimens from different body compartments. Sci Rep. 2014;4:5658.CrossRefPubMedPubMedCentral
38.
Hawken M, Nunn P, Gathua S, Brindle R, Godfrey-Faussett P, Githui W, Odhiambo J, Batchelor B, Gilks C, Morris J, et al. Increased recurrence of tuberculosis in HIV-1-infected patients in Kenya. Lancet. 1993;342(8867):332–7.CrossRefPubMed
39.
Driver CR, Munsiff SS, Li J, Kundamal N, Osahan SS. Relapse in persons treated for drug-susceptible tuberculosis in a population with high coinfection with human immunodeficiency virus in New York City. Clin Infect Dis. 2001;33(10):1762–9.CrossRefPubMed
40.
Fitzgerald DW, Desvarieux M, Severe P, Joseph P, Johnson Jr WD, Pape JW. Effect of post-treatment isoniazid on prevention of recurrent tuberculosis in HIV-1-infected individuals: a randomised trial. Lancet. 2000;356(9240):1470–4.CrossRefPubMed
41.
Shah M, Chihota V, Coetzee G, Churchyard G, Dorman SE. Comparison of laboratory costs of rapid molecular tests and conventional diagnostics for detection of tuberculosis and drug-resistant tuberculosis in South Africa. BMC Infect Dis. 2013;13:352.CrossRefPubMedPubMedCentral
42.
Jannetto PJ, Fitzerald RL. Effective use of mass spectrometry in the clinical laboratory. Clin Chem. 2016;62(1):92–8.CrossRefPubMed
43.
Li LF, Chen TC, Ren Y, Hendricks PI, Cooks RG, Ouyang Z. Mini 12, miniature mass spectrometer for clinical and other applications—introduction and characterization. Anal Chem. 2014;86(6):2909–16.CrossRefPubMedPubMedCentral
Metadata
Title
Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area
Authors
Jia Fan
Hedong Zhang
Duc T. Nguyen
Christopher J. Lyon
Charles D. Mitchell
Zhen Zhao
Edward A. Graviss
Ye Hu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0952-z

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