title: Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting.
abstract: 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-γ) 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-γ responses to TB rpfs show promise as TB diagnostic candidates and should be evaluated further for discrimination between M.tb infection states.
authors.affiliation: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa. novel@sun.ac.za
authors.forename: Novel N
authors.initials: NN
authors.lastname: Chegou
authors.forename: Gillian F
authors.initials: GF
authors.lastname: Black
authors.forename: Andre G
authors.initials: AG
authors.lastname: Loxton
authors.forename: Kim
authors.initials: K
authors.lastname: Stanley
authors.forename: Paulin N
authors.initials: PN
authors.lastname: Essone
authors.forename: Michel R
authors.initials: MR
authors.lastname: Klein
authors.forename: Shreemanta K
authors.initials: SK
authors.lastname: Parida
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.forename: Annemieke H
authors.initials: AH
authors.lastname: Friggen
authors.forename: Kees L
authors.initials: KL
authors.lastname: Franken
authors.forename: Tom H
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D013019:South Africa; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma