title: Comparing Tuberculosis Diagnostic Yield in Smear/Culture and Xpert® MTB/RIF-Based Algorithms Using a Non-Randomised Stepped-Wedge Design.
abstract: METHODS
  Primary health services in Cape Town, South Africa.
  
  
  OBJECTIVE
  To compare tuberculosis (TB) diagnostic yield in an existing smear/culture-based and a newly introduced Xpert® MTB/RIF-based algorithm.
  
  
  METHODS
  TB diagnostic yield (the proportion of presumptive TB cases with a laboratory diagnosis of TB) was assessed using a non-randomised stepped-wedge design as sites transitioned to the Xpert® based algorithm. We identified the full sequence of sputum tests recorded in the electronic laboratory database for presumptive TB cases from 60 primary health sites during seven one-month time-points, six months apart. Differences in TB yield and temporal trends were estimated using a binomial regression model.
  
  
  RESULTS
  TB yield was 20.9% (95% CI 19.9% to 22.0%) in the smear/culture-based algorithm compared to 17.9% (95%CI 16.4% to 19.5%) in the Xpert® based algorithm. There was a decline in TB yield over time with a mean risk difference of -0.9% (95% CI -1.2% to -0.6%) (p<0.001) per time-point. When estimates were adjusted for the temporal trend, TB yield was 19.1% (95% CI 17.6% to 20.5%) in the smear/culture-based algorithm compared to 19.3% (95% CI 17.7% to 20.9%) in the Xpert® based algorithm with a risk difference of 0.3% (95% CI -1.8% to 2.3%) (p = 0.796). Culture tests were undertaken for 35.5% of smear-negative compared to 17.9% of Xpert® negative low MDR-TB risk cases and for 82.6% of smear-negative compared to 40.5% of Xpert® negative high MDR-TB risk cases in respective algorithms.
  
  
  CONCLUSIONS
  Introduction of an Xpert® based algorithm did not produce the expected increase in TB diagnostic yield. Studies are required to assess whether improving adherence to the Xpert® negative algorithm for HIV-infected individuals will increase yield. In light of the high cost of Xpert®, a review of its role as a screening test for all presumptive TB cases may be warranted.
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Pren
authors.initials: P
authors.lastname: Naidoo
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Rory
authors.initials: R
authors.lastname: Dunbar
authors.affiliation: Biostatistics Unit, South African Medical Research Council, Cape Town, South Africa.
authors.forename: Carl
authors.initials: C
authors.lastname: Lombard
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: du Toit
authors.affiliation: City of Cape Town Health Directorate, Cape Town, South Africa.
authors.forename: Judy
authors.initials: J
authors.lastname: Caldwell
authors.affiliation: The International Union against TB and Lung Disease, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Detjen
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: S Bertel
authors.initials: SB
authors.lastname: Squire
authors.affiliation: The International Union against TB and Lung Disease, Paris, France.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Enarson
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Nulda
authors.initials: N
authors.lastname: Beyers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D019411:Clinical Laboratory Techniques / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*; D055815:Young Adult