title: Randomised clinical trial investigating the specificity of a novel skin test (C-Tb) for diagnosis of M. tuberculosis infection.
abstract: BACKGROUND
  Tuberculin skin testing is simple and relatively inexpensive, but the specificity of PPD is affected by BCG vaccination.
  
  
  OBJECTIVE
  Determine optimal dose and specificity of recombinant ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection.
  
  
  METHODS
  In a dose finding phase I trial 0.01 or 0.1 µg preserved and unpreserved C-Tb was injected by Mantoux technique in 38 patients with active tuberculosis and induration responses measured. In a phase II specificity trial in 151 uninfected, BCG vaccinated participants 0.1 µg C-Tb was compared to 2 TU PPD.
  
  
  RESULTS
  0.1 µg C-Tb gave a median induration of 15 mm after 2 days. Phenol preservation did not affect the response. The specificity of C-Tb was 99.3% (95% CI 96-100%) regarding indurations ≥5 mm as a positive outcome. This was higher than the specificity of PPD (63% using a cut-off of 5 mm or 92% using a cut-off of 15 mm to adjust for non-specific BCG responses). Local adverse reactions following C-Tb injection included transient itching and discomfort as expected components of the immune response.
  
  
  CONCLUSIONS
  C-Tb offers a simple and convenient skin test to diagnose M. tuberculosis infection using a single, universal cut-off unaffected by BCG vaccination.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01033929 and NCT01241188.
authors.affiliation: Department of Vaccine Development, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Aggerbeck
authors.forename: Rafaela
authors.initials: R
authors.lastname: Giemza
authors.forename: Paulatsya
authors.initials: P
authors.lastname: Joshi
authors.forename: Pernille N
authors.initials: PN
authors.lastname: Tingskov
authors.forename: Søren T
authors.initials: ST
authors.lastname: Hoff
authors.forename: Julia
authors.initials: J
authors.lastname: Boyle
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: David J M
authors.initials: DJ
authors.lastname: Lewis
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D001426:Bacterial Proteins / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology*; D019800:Phenol / Q000737:chemistry; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000009:adverse effects / Q000379:methods*; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D019800:Phenol