Microbiology Spectrum (Jun 2022)

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

  • G. Günther,
  • E. Saathoff,
  • A. Rachow,
  • H. Ekandjo,
  • A. Diergaardt,
  • N. Marais,
  • C. Lange,
  • E. Nepolo

DOI
https://doi.org/10.1128/spectrum.00259-22
Journal volume & issue
Vol. 10, no. 3

Abstract

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ABSTRACT 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.

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