title: Clinical significance of lipoarabinomannan detection in urine using a low-cost point-of-care diagnostic assay for HIV-associated tuberculosis.
abstract: OBJECTIVE
  A low-cost point-of-care urine assay for lipoarabinomannan (LAM) used for screening patients prior to antiretroviral therapy (ART) rapidly diagnoses a proportion of tuberculosis (TB) cases. We determined the characteristics and outcomes of such patients.
  
  
  METHODS
  Adults enrolling in a South African township ART clinic were systematically screened for pulmonary TB by testing paired sputum samples using microscopy, liquid culture and Xpert MTB/RIF in a centralized laboratory. Stored urine samples were retrospectively tested for LAM using the Determine TB-LAM assay, but results did not inform treatment. Patients were followed up in the routine ART service and early (90-day) programmatic outcomes were determined. Analysis was restricted to those with CD4 cell counts below 200 cells/μl.
  
  
  RESULTS
  Of patients with CD4 cell counts below 200 cells/μl and complete results (n=325), 59 (18.2%) had culture-positive TB. Of these, 23 (39%) patients tested urine LAM-positive and 36 (61%) urine LAM-negative. Patients with LAM-positive TB had much lower CD4 cell counts, higher plasma viral loads, lower haemoglobin concentrations and lower BMIs compared to those with LAM-negative TB. They also had evidence of higher mycobacterial load, more frequently testing sputum smear-positive, Xpert-positive (sputum and urine) and having a shorter time to sputum culture positivity. Of five (8.5%) patients who died, four did so before TB treatment was started. All five retrospectively tested LAM-positive.
  
  
  CONCLUSIONS
  A low-cost point-of-care urine test for LAM rapidly diagnoses a sub-group of cases with advanced HIV-associated TB and poor prognosis. If used in combination with laboratory-based diagnostics, treatment delays would decrease and survival might be improved.
authors.affiliation: The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. stevelawn@yahoo.co.uk
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kerkhoff
authors.forename: Monica
authors.initials: M
authors.lastname: Vogt
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D006679:HIV Seropositivity / Q000382:microbiology* / Q000652:urine*; D006801:Humans; D008070:Lipopolysaccharides / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D019095:Point-of-Care Systems / Q000191:economics; D011446:Prospective Studies; D013019:South Africa; D013183:Sputum / Q000382:microbiology*; D014376:Tuberculosis / Q000175:diagnosis / Q000652:urine*
chemical_list: D008070:Lipopolysaccharides; C050016:lipoarabinomannan