title: Performance of a Novel Algorithm Using Automated Digital Microscopy for Diagnosing Tuberculosis.
abstract: BACKGROUND
  TBDx automated microscopy is a novel technology that processes digital microscopic images to identify acid-fast bacilli (AFB). Use of TBDx as part of a diagnostic algorithm could improve the diagnosis of tuberculosis (TB), but its performance characteristics have not yet been formally tested.
  
  
  OBJECTIVE
  To evaluate the performance of the TBDx automated microscopy system in algorithms for diagnosis of TB.
  
  
  METHODS
  Prospective samples from patients with presumed TB were processed in parallel with conventional smear microscopy, TBDx microscopy, and liquid culture. All TBDx-positive specimens were also tested with the Xpert MTB/RIF (GXP) assay. We evaluated the sensitivity and specificity of two algorithms-(1) TBDx-GXP (TBDx with positive specimens tested by Xpert MTB/RIF) and (2) TBDx alone-against the gold standard liquid media culture.
  
  
  RESULTS
  Of 1,210 samples, 1,009 were eligible for evaluation, of which 109 were culture positive for Mycobacterium tuberculosis. The TBDx system identified 70 specimens (68 culture positive) as having 10 or more putative AFB (high positive) and 207 (19 culture positive) as having 1-9 putative AFB (low positive). An algorithm in which "low-positive" results on TBDx were confirmed by GXP had 78% sensitivity (85 of 109) and 99.8% specificity (889 of 900), requiring 21% (207 of 1,009) specimens to be processed by GXP. As a stand-alone test, a "high-positive" result on TBDx had 62% sensitivity and 99.7% specificity.
  
  
  CONCLUSIONS
  TBDx used in diagnostic algorithms with GXP provided reasonable sensitivity and high specificity for active TB while dramatically reducing the number GXP tests performed. As a stand-alone microscopy system, its performance was equivalent to that of a highly experienced TB microscopist.
authors.affiliation: 1 Centre for Tuberculosis, National Institute for Communicable Diseases, Sandringham, South Africa.|2 University of Pretoria, Pretoria, South Africa.
authors.forename: Nazir A
authors.initials: NA
authors.lastname: Ismail
authors.affiliation: 1 Centre for Tuberculosis, National Institute for Communicable Diseases, Sandringham, South Africa.
authors.forename: Shaheed V
authors.initials: SV
authors.lastname: Omar
authors.affiliation: 3 London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lewis
authors.affiliation: 4 Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: David W
authors.initials: DW
authors.lastname: Dowdy
authors.affiliation: 1 Centre for Tuberculosis, National Institute for Communicable Diseases, Sandringham, South Africa.|5 Department of Clinical Microbiology and Infectious Diseases and.
authors.forename: Andries W
authors.initials: AW
authors.lastname: Dreyer
authors.affiliation: 6 Aurum Institute, Johannesburg, South Africa.
authors.forename: Hermina
authors.initials: H
authors.lastname: van der Meulen
authors.affiliation: 1 Centre for Tuberculosis, National Institute for Communicable Diseases, Sandringham, South Africa.
authors.forename: George
authors.initials: G
authors.lastname: Nconjana
authors.affiliation: 6 Aurum Institute, Johannesburg, South Africa.
authors.forename: David A
authors.initials: DA
authors.lastname: Clark
authors.affiliation: 3 London School of Hygiene and Tropical Medicine, London, United Kingdom.|7 School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; and.|6 Aurum Institute, Johannesburg, South Africa.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Churchyard
mesh_terms: D000465:Algorithms; D006801:Humans; D008853:Microscopy / Q000295:instrumentation* / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000382:microbiology* / Q000473:pathology*
keywords: TBDx; Xpert; microscopy; triage; tuberculosis