Clinical utility of a novel molecular assay in various combination strategies with existing methods for diagnosis of HIV-related tuberculosis in Uganda

Willy Ssengooba, Lydia Nakiyingi, Derek T. Armstrong, Frank G. Cobelens, David Alland, Yukari C. Manabe, Susan E. Dorman, Jerrold J. Ellner, Moses L. Joloba

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere107595
JournalPloS one
Volume9
Issue number9
DOIs
StatePublished - Sep 15 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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