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 journalArticle

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

Fingerprint

Uganda
tuberculosis
Microscopy
Assays
microscopy
Microscopic examination
Tuberculosis
HIV
assays
methodology
Growth
Mycobacterium tuberculosis
CD4 Lymphocyte Count
Sputum
Pulmonary Tuberculosis
confidence interval
income
lungs
Confidence Intervals
Costs and Cost Analysis

ASJC Scopus subject areas

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

Cite this

Clinical utility of a novel molecular assay in various combination strategies with existing methods for diagnosis of HIV-related tuberculosis in Uganda. / Ssengooba, Willy; Nakiyingi, Lydia; Armstrong, Derek T.; Cobelens, Frank G.; Alland, David; Manabe, Yukari C; Dorman, Susan E.; Ellner, Jerrold J.; Joloba, Moses L.

In: PLoS One, Vol. 9, No. 9, e107595, 15.09.2014.

Research output: Contribution to journalArticle

Ssengooba, Willy ; Nakiyingi, Lydia ; Armstrong, Derek T. ; Cobelens, Frank G. ; Alland, David ; Manabe, Yukari C ; Dorman, Susan E. ; Ellner, Jerrold J. ; Joloba, Moses L. / Clinical utility of a novel molecular assay in various combination strategies with existing methods for diagnosis of HIV-related tuberculosis in Uganda. In: PLoS One. 2014 ; Vol. 9, No. 9.
@article{63b2700dd57c40cda079404f2b8a1e6a,
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.",
author = "Willy Ssengooba and Lydia Nakiyingi and Armstrong, {Derek T.} and Cobelens, {Frank G.} and David Alland and Manabe, {Yukari C} and Dorman, {Susan E.} and Ellner, {Jerrold J.} and Joloba, {Moses L.}",
year = "2014",
month = "9",
day = "15",
doi = "10.1371/journal.pone.0107595",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Clinical utility of a novel molecular assay in various combination strategies with existing methods for diagnosis of HIV-related tuberculosis in Uganda

AU - Ssengooba, Willy

AU - Nakiyingi, Lydia

AU - Armstrong, Derek T.

AU - Cobelens, Frank G.

AU - Alland, David

AU - Manabe, Yukari C

AU - Dorman, Susan E.

AU - Ellner, Jerrold J.

AU - Joloba, Moses L.

PY - 2014/9/15

Y1 - 2014/9/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907168986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907168986&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0107595

DO - 10.1371/journal.pone.0107595

M3 - Article

C2 - 25222866

AN - SCOPUS:84907168986

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e107595

ER -