title: Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria.
abstract: BACKGROUND
  Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection.
  
  
  METHODS
  LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay.
  
  
  RESULTS
  32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and < 50 cells/μl, was 15.2%, 32%, 42.9%, and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM positive patients and in none of the LAM negative controls.
  
  
  CONCLUSIONS
  Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Kimberly
authors.initials: K
authors.lastname: Racow
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Keren
authors.initials: K
authors.lastname: Middelkoop
authors.forename: Monica
authors.initials: M
authors.lastname: Vogt
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000032:analysis; D001437:Bacteriuria / Q000175:diagnosis*; D016172:DNA Fingerprinting; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000032:analysis*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D012150:Polymorphism, Restriction Fragment Length; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology; D014556:Urine / Q000737:chemistry* / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D008070:Lipopolysaccharides; C050016:lipoarabinomannan