title: Clinical utility of a novel molecular assay in various combination strategies with existing methods for diagnosis of HIV-related tuberculosis in Uganda.
abstract: BACKGROUND
  Low income, high-tuberculosis burden, countries are considering selective deployment of Xpert MTB/RIF assay (Xpert) due to high cost per test. We compared the diagnostic gain of the Xpert add-on strategy with Xpert replacement strategy for pulmonary tuberculosis diagnosis among HIV-infected adults to inform its implementation.
  
  
  METHODS
  The first diagnostic sputum sample of 424 HIV-infected adults (67% with CD4 counts ≤200/mm3) suspected for tuberculosis was tested by direct Ziehl-Neelsen (DZN) and direct fluorescent microscopy (DFM); concentrated fluorescent microscopy (CFM); Lowenstein-Jensen (LJ) and Mycobacterial Growth Indicator Tube (MGIT) culture; and Xpert. Overall diagnostic yield and sensitivity were calculated using MGIT as reference comparator. The sensitivity of Xpert in an add-on strategy was calculated as the number of smear negative but Xpert positive participants among MGIT positive participants.
  
  
  RESULTS
  A total of 123 (29.0%) participants were MGIT culture positive for Mycobacterium tuberculosis. The sensitivity (95% confidence interval) was 31.7% (23.6-40.7%) for DZN, 35.0% (26.5-44.0%) for DFM, 43.9% (34.9-53.1%) for CFM, 76.4% (67.9-83.6) for Xpert and 81.3% (73.2-87.7%) for LJ culture. Add-on strategy Xpert showed an incremental sensitivity of 44.7% (35.7-53.9%) when added to DZN, 42.3% (33.4-51.5%) to DFM and 35.0% (26.5-44.0%) to CFM. This translated to an overall sensitivity of 76.4%, 77.3% and 79.0% for add-on strategies based on DZN, DFM and CFM, respectively, compared to 76.4% for Xpert done independently. From replacement to add-on strategy, the number of Xpert cartridges needed was reduced by approximately 10%.
  
  
  CONCLUSIONS
  Among HIV-infected TB suspects, doing smear microscopy prior to Xpert assay in add-on fashion only identifies a few additional TB cases.
authors.affiliation: Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda; Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Willy
authors.initials: W
authors.lastname: Ssengooba
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakiyingi
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Derek T
authors.initials: DT
authors.lastname: Armstrong
authors.affiliation: Department of Global Health and Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; KNCV Tuberculosis Foundation, The Hague, Netherlands.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Cobelens
authors.affiliation: Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Alland
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Dorman
authors.affiliation: Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.affiliation: Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda; Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: Moses L
authors.initials: ML
authors.lastname: Joloba
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000302:isolation & purification* / Q000472:pathogenicity; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000209:etiology / Q000382:microbiology* / Q000473:pathology