This section provides brief descriptions of WHO-reviewed technologies for the detection of TB and DR-TB, summarizes WHO recommendations for such technologies and refers to WHO policy statements for each test and the WHO Consolidated guidelines on tuberculosis Module 3: Diagnosis - rapid diagnostics for tuberculosis detection 2021 update (5)⁴ for a thorough discussion of the technologies and recommendations.
The latest guidelines have added three new classes of NAAT technologies, as shown in Table 2.1.
The change from product-specific recommendations (e.g. Xpert MTB/RIF or Truenat MTB) to class-based recommendations (e.g. low complexity automated NAATs) is new. Hence, we are in a transitionary period where the previous product-based recommendations have not yet been integrated into the new classes. Integration of previously recommended products into the new classes needs to take into account the product-specific recommendations that, although similar, do differ, particularly for subgroups. The aim is that future updates will consolidate all products into classes.
The WHO-recommended tests have also been reorganized to clearly delineate the intended use, as per the recommendations. The new organizational structure is:
- initial tests for diagnosis of TB:
- with drug-resistance detection;
- without drug-resistance detection; and
- follow-on diagnostic tests after TB confirmation.
The initial tests for the diagnosis of TB are broadly grouped as WHO-approved rapid diagnostic tests (WRDs); these are defined as diagnostic tests that employ molecular or biomarker-based techniques for the diagnosis of TB (10).⁵ The newer, rapid and sensitive molecular tests recommended for the initial detection of MTBC and drug resistance are designated as mWRDs; they include Xpert MTB/RIF Ultra and Xpert MTB/RIF (Cepheid, Sunnyvale, United States of America [USA]); Truenat MTB, MTB Plus and MTB-RIF Dx tests (Molbio Diagnostics, Goa, India); and loop-mediated isothermal amplification (TB-LAMP; Eiken Chemical, Tokyo, Japan).
Also included as mWRDs are the new class of NAATs; that is, the automated moderate complexity NAATs, which detect not only TB and RIF resistance but also INH resistance. The four products evaluated and included in this class are Abbott RealTime MTB and MTB RIF/INH assays (Abbott Laboratories, Abbott Park, USA), the BD MAX MDR-TB assay (Becton, Dickinson and Company, Franklin Lakes, USA), the Hain FluoroType MTBDR assay (Bruker/Hain Lifescience, Nehren, Germany) and the Roche cobas MTB and MTB-RIF/INH assays (Hoffmann-La Roche, Basel, Switzerland).
In addition, the biomarker-based lateral flow lipoarabinomannan assay (LF-LAM) test (Alere Determine TB LAM Ag, USA) is recommended to assist in diagnosing TB in selected groups of HIV-infected presumptive-TB patients. A positive LF-LAM result is considered as bacteriological confirmation of TB in these patients (11),⁶ and this test is also included as a WRD.
WHO has reviewed and approved each of these tests, and has developed recommendations for their use. In all settings, WHO recommends that rapid techniques be used as the initial diagnostic test to detect MTBC and RIF resistance, to minimize delays in starting appropriate treatment.
The follow-on tests include line-probe assays (LPAs) for detection of resistance to RIF and INH (GenoType MTBDRplus, Bruker/Hain Lifescience, Nehren, Germany; NTM+MDRTB Detection Kit, NIPRO Corporation, Osaka, Japan) and to FQs and second-line injectables agents (GenoType MTBDRsl, Bruker/Hain Lifescience, Nehren, Germany). The two new classes added as follow-on tests include the low complexity automated NAATs for the detection of INH, FQs, ETO and AMK resistance (first in class: Xpert MTB/XDR [Cepheid, Sunnyvale, USA]) and the high complexity reverse hybridization NAAT for the detection of PZA resistance (first in class: Genoscholar PZA-TB II [NIPRO Corporation, Osaka, Japan]).
NAAT: nucleic acid amplification test; TB: tuberculosis.
⁴ See https://apps.who.int/iris/bitstream/handle/10665/342331/9789240029415-eng.pdf
⁵ See https://apps.who.int/iris/bitstream/handle/10665/79199/9789241505345_eng.pdf;jsessionid=FD522CF3B90C25716F 96288BFDEA6C75?sequence=1
⁶ See https://apps.who.int/iris/bitstream/handle/10665/79199/9789241505345_eng.pdf?sequence=1