title: Xpert MTB/RIF Results in Patients With Previous Tuberculosis: Can We Distinguish True From False Positive Results?
abstract: BACKGROUND
  Patients with previous tuberculosis may have residual DNA in sputum that confounds nucleic acid amplification tests such as Xpert MTB/RIF. Little is known about the frequency of Xpert-positive, culture-negative ("false positive") results in retreatment patients, whether these are distinguishable from true positives, and whether Xpert's automated filter-based wash step reduces false positivity by removing residual DNA associated with nonintact cells.
  
  
  METHODS
  Pretreatment patients (n = 2889) with symptoms of tuberculosis from Cape Town, South Africa, underwent a sputum-based liquid culture and Xpert. We also compared Xpert results from dilutions of intact or heat-lysed and mechanically lysed bacilli.
  
  
  RESULTS
  Retreatment cases were more likely to be Xpert false-positive (45/321 Xpert-positive retreatment cases were false-positive) than new cases (40/461) (14% [95% confidence interval {CI}, 10%-18%] vs 8% [95% CI, 6%-12%];P= .018). Fewer years since treatment completion (adjusted odds ratio [aOR], 0.85 [95% CI, .73-.99]), less mycobacterial DNA (aOR, 1.14 [95% CI, 1.03-1.27] per cycle threshold [CT]), and a chest radiograph not suggestive of active tuberculosis (aOR, 0.22 [95% CI, .06-.82]) were associated with false positivity. CThad suboptimal accuracy for false positivity: 46% of Xpert-positives with CT> 30 would be false positive, although 70% of false positives would be missed. CT's predictive ability (area under the curve, 0.83 [95% CI, .76-.90]) was not improved by additional variables. Xpert detected nonviable, nonintact bacilli without a change in CTvs controls.
  
  
  CONCLUSIONS
  One in 7 Xpert-positive retreatment patients were culture negative and potentially false positive. False positivity was associated with recent previous tuberculosis, high CT, and a chest radiograph not suggestive of active tuberculosis. Clinicians may consider awaiting confirmatory testing in retreatment patients with CT> 30; however, most false positives fall below this cut-point. Xpert can detect DNA from nonviable, nonintact bacilli.
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town and.|DST/NRF of Excellence for Biomedical Tuberculosis Research, and MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Grant
authors.initials: G
authors.lastname: Theron
authors.affiliation: DST/NRF of Excellence for Biomedical Tuberculosis Research, and MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Rouxjeane
authors.initials: R
authors.lastname: Venter
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Townand.
authors.forename: Greg
authors.initials: G
authors.lastname: Calligaro
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Townand.
authors.forename: Liezel
authors.initials: L
authors.lastname: Smith
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Townand.
authors.forename: Jason
authors.initials: J
authors.lastname: Limberis
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Townand.
authors.forename: Richard
authors.initials: R
authors.lastname: Meldau
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town and.|Institute for Medical Research and Training, Lusaka, Zambia.
authors.forename: Duncan
authors.initials: D
authors.lastname: Chanda
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Townand.
authors.forename: Aliasgar
authors.initials: A
authors.lastname: Esmail
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Townand.
authors.forename: Jonny
authors.initials: J
authors.lastname: Peter
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town and.|Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
mesh_terms: D000328:Adult; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification; D021141:Nucleic Acid Amplification Techniques; D012372:ROC Curve; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology
chemical_list: D004269:DNA, Bacterial; D011933:Reagent Kits, Diagnostic
keywords: Xpert; diagnosis; false positivity; tuberculosis