title: Implementation and Operational Research: What Happens After a Negative Test for Tuberculosis? Evaluating Adherence to TB Diagnostic Algorithms in South African Primary Health Clinics.
abstract: BACKGROUND
  Diagnostic tests for tuberculosis (TB) using sputum have suboptimal sensitivity among HIV-positive persons. We assessed health care worker adherence to TB diagnostic algorithms after negative sputum test results.
  
  
  METHODS
  The XTEND (Xpert for TB-Evaluating a New Diagnostic) trial compared outcomes among people tested for TB in primary care clinics using Xpert MTB/RIF vs. smear microscopy as the initial test. We analyzed data from XTEND participants who were HIV positive or HIV status unknown, whose initial sputum Xpert MTB/RIF or microscopy result was negative. If chest radiography, sputum culture, or hospital referral took place, the algorithm for TB diagnosis was considered followed. Analysis of intervention (Xpert MTB/RIF) effect on algorithm adherence used methods for cluster-randomized trials with small number of clusters.
  
  
  RESULTS
  Among 4037 XTEND participants with initial negative test results, 2155 (53%) reported being or testing HIV positive and 540 (14%) had unknown HIV status. Among 2155 HIV-positive participants [684 (32%) male, mean age 37 years (range, 18-79 years)], there was evidence of algorithm adherence among 515 (24%). Adherence was less likely among persons tested initially with Xpert MTB/RIF vs. smear [14% (142/1031) vs. 32% (364/1122), adjusted risk ratio 0.34 (95% CI: 0.17 to 0.65)] and for participants with unknown vs. positive HIV status [59/540 (11%) vs. 507/2155 (24%)].
  
  
  CONCLUSIONS
  We observed poorer adherence to TB diagnostic algorithms among HIV-positive persons tested initially with Xpert MTB/RIF vs. microscopy. Poor adherence to TB diagnostic algorithms and incomplete coverage of HIV testing represents a missed opportunity to diagnose TB and HIV, and may contribute to TB mortality.
authors.affiliation: *The Aurum Institute; Johannesburg, South Africa; †School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; ‡London School of Hygiene and Tropical Medicine, London, United Kingdom; and §South African National TB Control Programme, National Department of Health, Pretoria, South Africa.
authors.forename: K M
authors.initials: KM
authors.lastname: McCarthy
authors.forename: A D
authors.initials: AD
authors.lastname: Grant
authors.forename: V
authors.initials: V
authors.lastname: Chihota
authors.forename: S
authors.initials: S
authors.lastname: Ginindza
authors.forename: L
authors.initials: L
authors.lastname: Mvusi
authors.forename: G J
authors.initials: GJ
authors.lastname: Churchyard
authors.forename: K L
authors.initials: KL
authors.lastname: Fielding
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D003661:Decision Support Techniques; D003955:Diagnostic Tests, Routine; D005260:Female; D019983:Guideline Adherence / Q000592:standards*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods / Q000592:standards*; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D009874:Operations Research; D013019:South Africa; D013183:Sputum / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*; D055815:Young Adult