title: Xpert MTB/RIF versus sputum microscopy as the initial diagnostic test for tuberculosis: a cluster-randomised trial embedded in South African roll-out of Xpert MTB/RIF.
abstract: BACKGROUND
  In South Africa, sputum smear microscopy has been replaced with Xpert MTB/RIF as the initial diagnostic test for tuberculosis. In a pragmatic parallel cluster-randomised trial, we evaluated the effect on patient and programme outcomes.
  
  
  METHODS
  We randomly allocated 20 laboratories (clusters) in medium-burden districts of South Africa to either an Xpert (immediate Xpert) or microscopy (Xpert deferred) group (1:1), stratified by province. At two primary care clinics per laboratory, a systematic sample of adults giving sputum for tuberculosis investigation was assessed for eligibility. The primary outcome was mortality at 6 months from enrolment. Masking of participants' group allocation was not possible because of the pragmatic trial design. The trial is registered with the ISRCTN registry (ISRCTN68905568) and the South African Clinical Trial Register (DOH-27-1011-3849).
  
  
  RESULTS
  Between June and November, 2012, 4972 people were screened, and 4656 (93·6%) enrolled (median age 36 years; 2891 [62%] female; 2212 [62%] reported being HIV-positive). There was no difference between the Xpert and microscopy groups with respect to mortality at 6 months (91/2324 [3·9%] vs 116/2332 [5·0%], respectively; adjusted risk ratio [aRR] 1·10, 95% CI 0·75-1·62]).
  
  
  CONCLUSIONS
  Xpert did not reduce mortality at 6 months compared with sputum microscopy. Improving outcomes in drug-sensitive tuberculosis programmes might require not only better diagnostic tests but also better linkage to care.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation.
authors.affiliation: Aurum Institute, Johannesburg, South Africa; London School of Hygiene & Tropical Medicine, London, United Kingdom; School of Public Health, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: gchurchyard@auruminstitute.org.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Churchyard
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa; Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.affiliation: TB Cluster, National Department of Health, South Africa.
authors.forename: Lerole D
authors.initials: LD
authors.lastname: Mametja
authors.affiliation: Aurum Institute, Johannesburg, South Africa.
authors.forename: Kerrigan M
authors.initials: KM
authors.lastname: McCarthy
authors.affiliation: Aurum Institute, Johannesburg, South Africa.
authors.forename: Violet
authors.initials: V
authors.lastname: Chihota
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa; Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nicol
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa; Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Linda K
authors.initials: LK
authors.lastname: Erasmus
authors.affiliation: TB Cluster, National Department of Health, South Africa.
authors.forename: Norbert O
authors.initials: NO
authors.lastname: Ndjeka
authors.affiliation: TB Cluster, National Department of Health, South Africa.
authors.forename: Lindiwe
authors.initials: L
authors.lastname: Mvusi
authors.affiliation: London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Vassall
authors.affiliation: Health Economics Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Edina
authors.initials: E
authors.lastname: Sinanovic
authors.affiliation: Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Cox
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dye
authors.affiliation: London School of Hygiene & Tropical Medicine, London, United Kingdom; School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Grant
authors.affiliation: London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Fielding
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000995:Antitubercular Agents / Q000627:therapeutic use; D015897:Comorbidity; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D023381:Endpoint Determination; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009026:Mortality / Q000639:trends; D010043:Outcome and Process Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D012293:Rifampin / Q000627:therapeutic use; D013019:South Africa; D013183:Sputum / Q000382:microbiology*; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin