4.7 Article

Diagnostic Accuracy Study of a Novel Blood-Based Assay for Identification of Tuberculosis in People Living with HIV

Journal

JOURNAL OF CLINICAL MICROBIOLOGY
Volume 59, Issue 3, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/JCM.01643-20

Keywords

3-gene; Cepheid; gene signature; Xpert; diagnostics; host response; human immunodeficiency virus; nonsputum; rapid tests; tuberculosis

Categories

Funding

  1. United Kingdom Department for International Development (DFID) [300341-102]
  2. Dutch Ministry of Foreign Affairs [PDP15CH14]
  3. Australian Department of Foreign Affairs and Trade (DFAT) [70957]
  4. German Federal Ministry of Education and Research (BMBF) through KfW [2020 62 156]
  5. Bill and Melinda Gates Foundation [OPP1113682]
  6. NIH/NIAID [5U19AI109662-05, 5R01AI125197-02, 5U19AI057229]
  7. Department of Defense [W81XWH-18-1-0253, W81XWH1910235]
  8. Ralph and Marian Falk Medical Research Trust
  9. U.S. Department of Defense (DOD) [W81XWH1910235] Funding Source: U.S. Department of Defense (DOD)

Ask authors/readers for more resources

This study evaluated the accuracy of an early-prototype cartridge assay for HIV patients and showed its potential value for triage and diagnosis in tuberculosis patients. The prototype showed promising results in discriminating TB from other illnesses and in comparison with other microbiological tests like Xpert MTB/RIF.
A nonsputum triage test to rule out tuberculosis (TB) disease is a WHO high-priority diagnostic, and a combinatory score based on a 3-gene host signature has shown promise in discriminating TB from other illnesses. We evaluated the accuracy of an early-prototype cartridge assay (Xpert MTB Host Response or Xpert-MTB-HR-Prototype) of this 3-gene signature on biobanked blood samples from people living with HIV (PLHIV) against a comprehensive microbiological reference standard (CMRS) and against Xpert MTB/RIF on the first sputum sample alone. We depict results based on performance targets set by the WHO in comparison with a laboratory-based C-reactive protein (CRP) assay. Of 201 patients included, 67 were culture positive for Mycobacterium tuberculosis. The areas under the concentration-time curve (AUCs) for Xpert-MTB-HR-Prototype were 0.89 (confidence interval [CI], 0.83 to 0.94) against the CMRS and 0.94 (CI, 0.89 to 0.98) against Xpert MTB/RIF. Considering Xpert-MTB-HR-Prototype as a triage test (at the nearest upper value of sensitivity to 90%), specificities were 55.8% (CI, 47.2 to 64.1%) compared to the CMRS and 85.9% (CI, 79.3 to 90.7%) compared to Xpert MTB/RIF as confirmatory tests. Considering Xpert-MTB-HR-Prototype as a stand-alone diagnostic test, at a specificity near 95%, the test achieved a sensitivity of 65.7% (CI, 53.7 to 75.9%), while the CRP assay achieved a sensitivity of only 13.6% (CI, 7.3 to 23.4%). In this first accuracy study of a prototype blood-based host marker assay, we show the possible value of the assay for triage and diagnosis in PLHIV.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available