Clinical Evaluation of a Line-Probe Assay for Tuberculosis Detection and Drug-Resistance Prediction in Namibia

Guenther, G.; Saathoff, E.; Rachow, A.; Ekandjo, H.; Diergaardt, A.; Marais, N.; Lange, C. und Nepolo, E. (2022): Clinical Evaluation of a Line-Probe Assay for Tuberculosis Detection and Drug-Resistance Prediction in Namibia. In: Microbiology Spectrum, Bd. 10, Nr. 3

Abstract

Mycobacterium tuberculosis (Mtb) drug-resistance detection is crucial for successful control of tuberculosis. Line-probe assays (LPA) are frequently used to detect resistance to rifampin, isoniazid, fluoroquinolones (FQs), and second-line injectables (SLIs). Treatment of tuberculosis requires rapid information about Mycobacterium tuberculosis (Mtb) drug susceptibility to ensure effective therapy and optimal outcomes. At the tuberculosis referral hospital in Windhoek, Namibia, a country of high tuberculosis incidence, we evaluated the diagnostic accuracy of a line-probe-assay (LPA), GenID, for the molecular diagnosis of Mtb infection and drug resistance in patients with suspected tuberculosis (cohort 1) and confirmed rifampin (RIF)-resistant tuberculosis (cohort 2). GenID test results were compared to Xpert MTB/RIF and/or Mtb culture and antimicrobial suceptibilty testing. GenID LPA was applied to 79 and 55 samples from patients in cohort 1 and cohort 2, respectively. The overall sensitivity of GenID LPA for the detection of Mtb DNA in sputum from patients with detectable and undetectable acid-fast bacilli by sputum smear microscopy was 93.3% (56/60;95% confidence interval = 83.8-98.2) and 22.7% (5/22;7.8-45.4). The sensitivity/specificity for the detection of drug resistance was 84.2% (32/38;68.7-94.0)/100% (19/19;82.4-100.0) for RIF, 89.7% (26/29;72.6-97.8)/91.7% (22/24;73.0-99.0) for isoniazid, and 85.7% (6/7;42.1-99.6)/94.7% (18/19;74.0-99.9) for fluoroquinolones;23.6% of tests for second-line injectable resistance were invalid despite repeat testing. The diagnosis of tuberculosis by detection of Mtb DNA in sputum by GenID LPA depends strongly on the detection of acid-fast bacilli in sputum specimen. Prediction of drug resistance by GenID did not reach the World Health Organization (WHO) target product profile. IMPORTANCE Mycobacterium tuberculosis (Mtb) drug-resistance detection is crucial for successful control of tuberculosis. Line-probe assays (LPA) are frequently used to detect resistance to rifampin, isoniazid, fluoroquinolones (FQs), and second-line injectables (SLIs). GenID RIF/isoniazid (INH), FQ, and SLI LPA have not been widely tested and used so far. This study tested the diagnostic performance of the GenID LPA in a high-incidence TB/HIV, real-world setting in Namibia. The LPA demonstrates only an acceptable diagnostic performance for Mtb and drug-resistance detection. The diagnostic sensitivity and specificity fall short of the WHO suggested target product profiles for LPA.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2165-0497
• Sprache: Englisch