title: Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial.
abstract: BACKGROUND
  Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden.
  
  
  RESULTS
  A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33-0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32-1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06-1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63-0.92, p = 0.005) and among HIV-infected participants (ITT analysis, hazard ratio 0.67, 95% CI 0.53-0.85, p = 0.001). There was no difference in 6-mo mortality with Xpert versus routine diagnosis. Study limitations included incorrect intervention allocation for a high proportion of participants and that the study was conducted in a single clinic.
  
  
  CONCLUSIONS
  These data suggest that in this routine primary care setting, use of Xpert to diagnose TB increased the number of individuals with bacteriologically confirmed TB who were treated by 3 mo and reduced time to treatment initiation, particularly among HIV-infected participants.
  
  
  BACKGROUND
  Pan African Clinical Trials Registry PACTR201010000255244. Please see later in the article for the Editors' Summary.
authors.affiliation: Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Médecins Sans Frontières, Khayelitsha, South Africa.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Cox
authors.affiliation: Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
authors.forename: Slindile
authors.initials: S
authors.lastname: Mbhele
authors.affiliation: Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
authors.forename: Neisha
authors.initials: N
authors.lastname: Mohess
authors.affiliation: Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Andrew
authors.initials: A
authors.lastname: Whitelaw
authors.affiliation: Médecins Sans Frontières, Khayelitsha, South Africa.
authors.forename: Odelia
authors.initials: O
authors.lastname: Muller
authors.affiliation: Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
authors.forename: Widaad
authors.initials: W
authors.lastname: Zemanay
authors.affiliation: Department of Statistical Science, University of Cape Town, Cape Town, South Africa.
authors.forename: Francesca
authors.initials: F
authors.lastname: Little
authors.affiliation: Khayelitsha Health, City of Cape Town, Cape Town, South Africa.
authors.forename: Virginia
authors.initials: V
authors.lastname: Azevedo
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: John
authors.initials: J
authors.lastname: Simpson
authors.affiliation: Foundation for Innovative New Diagnostics, Geneva, Switzerland.
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Boehme
authors.affiliation: Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nicol
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000554:Ambulatory Care Facilities; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D015995:Prevalence; D011320:Primary Health Care; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D012293:Rifampin / Q000627:therapeutic use; D013019:South Africa; D061665:Time-to-Treatment; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology; D055815:Young Adult
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin