title: Incremental Yield of Including Determine-TB LAM Assay in Diagnostic Algorithms for Hospitalized and Ambulatory HIV-Positive Patients in Kenya.
abstract: BACKGROUND
  Determine-TB LAM assay is a urine point-of-care test useful for TB diagnosis in HIV-positive patients. We assessed the incremental diagnostic yield of adding LAM to algorithms based on clinical signs, sputum smear-microscopy, chest X-ray and Xpert MTB/RIF in HIV-positive patients with symptoms of pulmonary TB (PTB).
  
  
  METHODS
  Prospective observational cohort of ambulatory (either severely ill or CD4<200cells/μl or with Body Mass Index<17Kg/m2) and hospitalized symptomatic HIV-positive adults in Kenya. Incremental diagnostic yield of adding LAM was the difference in the proportion of confirmed TB patients (positive Xpert or MTB culture) diagnosed by the algorithm with LAM compared to the algorithm without LAM. The multivariable mortality model was adjusted for age, sex, clinical severity, BMI, CD4, ART initiation, LAM result and TB confirmation.
  
  
  RESULTS
  Among 474 patients included, 44.1% were severely ill, 69.6% had CD4<200cells/μl, 59.9% had initiated ART, 23.2% could not produce sputum. LAM, smear-microscopy, Xpert and culture in sputum were positive in 39.0% (185/474), 21.6% (76/352), 29.1% (102/350) and 39.7% (92/232) of the patients tested, respectively. Of 156 patients with confirmed TB, 65.4% were LAM positive. Of those classified as non-TB, 84.0% were LAM negative. Adding LAM increased the diagnostic yield of the algorithms by 36.6%, from 47.4% (95%CI:39.4-55.6) to 84.0% (95%CI:77.3-89.4%), when using clinical signs and X-ray; by 19.9%, from 62.2% (95%CI:54.1-69.8) to 82.1% (95%CI:75.1-87.7), when using clinical signs and microscopy; and by 13.4%, from 74.4% (95%CI:66.8-81.0) to 87.8% (95%CI:81.6-92.5), when using clinical signs and Xpert. LAM positive patients had an increased risk of 2-months mortality (aOR:2.7; 95%CI:1.5-4.9).
  
  
  CONCLUSIONS
  LAM should be included in TB diagnostic algorithms in parallel to microscopy or Xpert request for HIV-positive patients either ambulatory (severely ill or CD4<200cells/μl) or hospitalized. LAM allows same day treatment initiation in patients at higher risk of death and in those not able to produce sputum.
authors.affiliation: Epicentre, Paris, France.
authors.forename: Helena
authors.identifier: http://orcid.org/0000-0003-0302-9063
authors.initials: H
authors.lastname: Huerga
authors.affiliation: Médecins Sans Frontières, Paris, France.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferlazzo
authors.affiliation: Epicentre, Paris, France.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bevilacqua
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Kirubi
authors.affiliation: Médecins Sans Frontières, Paris, France.|Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ardizzoni
authors.affiliation: Médecins Sans Frontières, Nairobi, Kenya.
authors.forename: Stephen
authors.initials: S
authors.lastname: Wanjala
authors.affiliation: Ministry of Health, Nairobi, Kenya.
authors.forename: Joseph
authors.initials: J
authors.lastname: Sitienei
authors.affiliation: Epicentre, Paris, France.|IRD UMI 233 TransVIHMI - UM - INSERM U1175, Montpellier, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Bonnet
mesh_terms: D000328:Adult; D000465:Algorithms; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007630:Kenya; D008070:Lipopolysaccharides / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D019095:Point-of-Care Systems; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000175:diagnosis*
chemical_list: D008070:Lipopolysaccharides; C050016:lipoarabinomannan