title: Diagnostic accuracy of a point-of-care urine test for tuberculosis screening among newly-diagnosed HIV-infected adults: a prospective, clinic-based study.
abstract: BACKGROUND
  A rapid diagnostic test for active tuberculosis (TB) at the clinical point-of-care could expedite case detection and accelerate TB treatment initiation. We assessed the diagnostic accuracy of a rapid urine lipoarabinomannan (LAM) test for TB screening among HIV-infected adults in a TB-endemic setting.
  
  
  METHODS
  We prospectively enrolled newly-diagnosed HIV-infected adults (≥18 years) at 4 outpatient clinics in Durban from Oct 2011-May 2012, excluding those on TB therapy. A physician evaluated all participants and offered CD4 cell count testing. Trained study nurses collected a sputum sample for acid-fast bacilli smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing using Determine™ TB LAM in the clinic. The presence of a band regardless of intensity on the urine LAM test was considered positive. We defined as the gold standard for active pulmonary TB a positive sputum culture for Mycobacterium tuberculosis. Diagnostic accuracy of urine LAM was assessed, alone and in combination with smear microscopy, and stratified by CD4 cell count.
  
  
  RESULTS
  Among 342 newly-diagnosed HIV-infected participants, 190 (56%) were male, mean age was 35.6 years, and median CD4 was 182/mm3. Sixty participants had culture-positive pulmonary TB, resulting in an estimated prevalence of 17.5% (95% CI 13.7-22.0%). Forty-five (13.2%) participants were urine LAM positive. Mean time from urine specimen collection to LAM test result was 40 minutes (95% CI 34-46 minutes). Urine LAM test sensitivity was 28.3% (95% CI 17.5-41.4) overall, and 37.5% (95% CI 21.1-56.3) for those with CD4 count <100/mm3, while specificity was 90.1% (95% CI 86.0-93.3) overall, and 86.9% (95% CI 75.8-94.2) for those with CD4 < 100/mm3. When combined with sputum AFB (either test positive), sensitivity increased to 38.3% (95% CI 26.0-51.8), but specificity decreased to 85.8% (95% CI 81.1-89.7).
  
  
  CONCLUSIONS
  In this prospective, clinic-based study with trained nurses, a rapid urine LAM test had low sensitivity for TB screening among newly-diagnosed HIV-infected adults, but improved sensitivity when combined with sputum smear microscopy.
authors.affiliation: Division of Infectious Diseases and Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, USA. pdrain@partners.org.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Drain
authors.forename: Elena
authors.initials: E
authors.lastname: Losina
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Coleman
authors.forename: Janet
authors.initials: J
authors.lastname: Giddy
authors.forename: Douglas
authors.initials: D
authors.lastname: Ross
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Katz
authors.forename: Rochelle P
authors.initials: RP
authors.lastname: Walensky
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Ingrid V
authors.initials: IV
authors.lastname: Bassett
mesh_terms: D000328:Adult; D000554:Ambulatory Care Facilities; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008070:Lipopolysaccharides / Q000652:urine*; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D019095:Point-of-Care Systems; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000175:diagnosis*; D016482:Urinalysis / Q000379:methods
chemical_list: D008070:Lipopolysaccharides; C050016:lipoarabinomannan