title: Microscopic-observation drug-susceptibility assay for the diagnosis of TB.
abstract: BACKGROUND
  New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid, sensitive detection of tuberculosis and multidrug-resistant tuberculosis in sputum has been demonstrated in proof-of-principle studies of the microscopic-observation drug-susceptibility (MODS) assay, in which broth cultures are examined microscopically to detect characteristic growth.
  
  
  METHODS
  In an operational setting in Peru, we investigated the performance of the MODS assay for culture and drug-susceptibility testing in three target groups: unselected patients with suspected tuberculosis, prescreened patients at high risk for tuberculosis or multidrug-resistant tuberculosis, and unselected hospitalized patients infected with the human immunodeficiency virus. We compared the MODS assay head-to-head with two reference methods: automated mycobacterial culture and culture on Löwenstein-Jensen medium with the proportion method.
  
  
  RESULTS
  Of 3760 sputum samples, 401 (10.7%) yielded cultures positive for Mycobacterium tuberculosis. Sensitivity of detection was 97.8% for MODS culture, 89.0% for automated mycobacterial culture, and 84.0% for Löwenstein-Jensen culture (P<0.001); the median time to culture positivity was 7 days, 13 days, and 26 days, respectively (P<0.001), and the median time to the results of susceptibility tests was 7 days, 22 days, and 68 days, respectively. The incremental benefit of a second MODS culture was minimal, particularly in patients at high risk for tuberculosis or multidrug-resistant tuberculosis. Agreement between MODS and the reference standard for susceptibility was 100% for rifampin, 97% for isoniazid, 99% for rifampin and isoniazid (combined results for multidrug resistance), 95% for ethambutol, and 92% for streptomycin (kappa values, 1.0, 0.89, 0.93, 0.71, and 0.72, respectively).
  
  
  CONCLUSIONS
  A single MODS culture of a sputum sample offers more rapid and sensitive detection of tuberculosis and multidrug-resistant tuberculosis than the existing gold-standard methods used.
authors.affiliation: Department of Infectious Diseases and Immunity and the Wellcome Centre for Clinical Tropical Medicine, Imperial College London, Faculty of Medicine (Hammersmith Campus), London, United Kingdom. davidajmoore@msn.com
authors.forename: David A J
authors.initials: DA
authors.lastname: Moore
authors.forename: Carlton A W
authors.initials: CA
authors.lastname: Evans
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Luz
authors.initials: L
authors.lastname: Caviedes
authors.forename: Jorge
authors.initials: J
authors.lastname: Coronel
authors.forename: Aldo
authors.initials: A
authors.lastname: Vivar
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sanchez
authors.forename: Yvette
authors.initials: Y
authors.lastname: Piñedo
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Saravia
authors.forename: Cayo
authors.initials: C
authors.lastname: Salazar
authors.forename: Richard
authors.initials: R
authors.lastname: Oberhelman
authors.forename: Maria-Graciela
authors.initials: MG
authors.lastname: Hollm-Delgado
authors.forename: Doris
authors.initials: D
authors.lastname: LaChira
authors.forename: A Roderick
authors.initials: AR
authors.lastname: Escombe
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
mesh_terms: D000328:Adult; D001431:Bacteriological Techniques; D005260:Female; D015658:HIV Infections; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods*; D008853:Microscopy; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology*; D014376:Tuberculosis / Q000175:diagnosis* / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000382:microbiology