title: Diagnostic accuracy of computer-aided detection of pulmonary tuberculosis in chest radiographs: a validation study from sub-Saharan Africa.
abstract: BACKGROUND
  Chest radiography to diagnose and screen for pulmonary tuberculosis has limitations, especially due to inter-reader variability. Automating the interpretation has the potential to overcome this drawback and to deliver objective and reproducible results. The CAD4TB software is a computer-aided detection system that has shown promising preliminary findings. Evaluation studies in different settings are needed to assess diagnostic accuracy and practicability of use.
  
  
  METHODS
  CAD4TB was evaluated on chest radiographs of patients with symptoms suggestive of pulmonary tuberculosis enrolled in two cohort studies in Tanzania. All patients were characterized by sputum smear microscopy and culture including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis (M.tb) to determine the reference standard. Chest radiographs were read by the software and two human readers, one expert reader and one clinical officer. The sensitivity and specificity of CAD4TB was depicted using receiver operating characteristic (ROC) curves, the area under the curve calculated and the performance of the software compared to the results of human readers.
  
  
  RESULTS
  Of 861 study participants, 194 (23%) were culture-positive for M.tb. The area under the ROC curve of CAD4TB for the detection of culture-positive pulmonary tuberculosis was 0.84 (95% CI 0.80-0.88). CAD4TB was significantly more accurate for the discrimination of smear-positive cases against non TB patients than for smear-negative cases (p-value<0.01). It differentiated better between TB cases and non TB patients among HIV-negative compared to HIV-positive individuals (p<0.01). CAD4TB significantly outperformed the clinical officer, but did not reach the accuracy of the expert reader (p = 0.02), for a tuberculosis specific reading threshold.
  
  
  CONCLUSIONS
  CAD4TB accurately distinguished between the chest radiographs of culture-positive TB cases and controls. Further studies on cost-effectiveness, operational and ethical aspects should determine its place in diagnostic and screening algorithms.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, United Republic of Tanzania; Center for Infectious Diseases and Travel Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Breuninger
authors.affiliation: Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: van Ginneken
authors.affiliation: Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Rick H H M
authors.initials: RH
authors.lastname: Philipsen
authors.affiliation: Ifakara Health Institute, Bagamoyo, United Republic of Tanzania.
authors.forename: Francis
authors.initials: F
authors.lastname: Mhimbira
authors.affiliation: Ifakara Health Institute, Bagamoyo, United Republic of Tanzania.
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Hella
authors.affiliation: Ifakara Health Institute, Bagamoyo, United Republic of Tanzania.
authors.forename: Fred
authors.initials: F
authors.lastname: Lwilla
authors.affiliation: PharmAccess International, Dar es Salaam, United Republic of Tanzania.
authors.forename: Jan
authors.initials: J
authors.lastname: van den Hombergh
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ross
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, United Republic of Tanzania; University of Basel, Basel, Switzerland.
authors.forename: Levan
authors.initials: L
authors.lastname: Jugheli
authors.affiliation: Center for Infectious Diseases and Travel Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wagner
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, United Republic of Tanzania; University of Basel, Basel, Switzerland.
authors.forename: Klaus
authors.initials: K
authors.lastname: Reither
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D005260:Female; D006679:HIV Seropositivity; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D013902:Radiography, Thoracic / Q000592:standards; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed; D014397:Tuberculosis, Pulmonary / Q000000981:diagnostic imaging*; D055815:Young Adult