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          Institute: MPI für Infektionsbiologie     Collection: Department of Immunology     Display Documents

ID: 608962.0, MPI für Infektionsbiologie / Department of Immunology
Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting
Authors:Chegou, Novel N.; Black, Gillian F.; Loxton, Andre G.; Stanley, Kim; Essone, Paulin N.; Klein, Michel R.; Parida, Shreemanta K.; Kaufmann, Stefan H. E.; Doherty, T. Mark; Friggen, Annemieke H.; Franken, Kees L.; Ottenhoff, Tom H.; Walzl, Gerhard
Date of Publication (YYYY-MM-DD):2012-01-20
Title of Journal:BMC Infectious Diseases
Journal Abbrev.:BMC Infect. Dis.
Sequence Number of Article:10
Copyright:©2012 Chegou et al; licensee BioMed Central Ltd.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Background: Confirming tuberculosis (TB) disease in suspects in resource limited settings is challenging and calls for the development of more suitable diagnostic tools. Different Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens may be differentially recognized in infected and diseased individuals and therefore useful as diagnostic tools for differentiating between M.tb infection states. In this study, we assessed the diagnostic potential of 118 different M.tb infection phase-dependent antigens in TB patients and household contacts (HHCs) in a high-burden setting. Methods: Antigens were evaluated using the 7-day whole blood culture technique in 23 pulmonary TB patients and in 19 to 21 HHCs (total n = 101), who were recruited from a high-TB incidence community in Cape Town, South Africa. Interferon-gamma (IFN-gamma) levels in culture supernatants were determined by ELISA. Results: Eight classical TB vaccine candidate antigens, 51 DosR regulon encoded antigens, 23 TB reactivation antigens, 5 TB resuscitation promoting factors (rpfs), 6 starvation and 24 other stress response-associated TB antigens were evaluated in the study. The most promising antigens for ascertaining active TB were the rpfs (Rv0867c, Rv2389c, Rv2450c, Rv1009 and Rv1884c), with Areas under the receiver operating characteristics curves (AUCs) between 0.72 and 0.80. A combination of M. tb specific ESAT-6/CFP-10 fusion protein, Rv2624c and Rv0867c accurately predicted 73% of the TB patients and 80% of the non-TB cases after cross validation. Conclusions: IFN-gamma responses to TB rpfs show promise as TB diagnostic candidates and should be evaluated further for discrimination between M. tb infection states.
Comment of the Author/Creator:This work received financial support from the Bill & Melinda Gates Foundation Grand Challenge 6 (BMGFGC6, grant no 37772), Principal Investigator SHE Kaufmann.
External Publication Status:published
Document Type:Article
Communicated by:Beate Löhr
Affiliations:MPI für Infektionsbiologie/Department of Immunology
External Affiliations:[Chegou, Novel N.; Black, Gillian F.; Loxton, Andre G.; Stanley, Kim; Essone, Paulin N.; Walzl, Gerhard] Univ Stellenbosch, Fac Hlth Sci, DST NRF Ctr Excellence Biomed TB Res, ZA-7505 Tygerberg, South Africa.; [Chegou, Novel N.; Black, Gillian F.; Loxton, Andre G.; Stanley, Kim; Essone, Paulin N.; Walzl, Gerhard] Univ Stellenbosch, Fac Hlth Sci, MRC Ctr Mol & Cellular Biol, Div Mol Biol & Human Genet,Dept Biomed Sci, ZA-7505 Tygerberg, South Africa.; [Klein, Michel R.; Friggen, Annemieke H.; Franken, Kees L.; Ottenhoff, Tom H.] Leiden Univ, Dept Infect Dis, Med Ctr, NL-2300 RC Leiden, Netherlands.;[Doherty, T. Mark] Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen S, Denmark.; [Doherty, T. Mark] GlaxoSmithKline Inc, Copenhagen, Denmark.
Identifiers:ISI:000300558300001 [ID No:1]
ISSN:1471-2334 [ID No:2]
DOI:10.1186/1471-2334-12-10 [ID NO:3]
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