Operational Handbooks

2.5.1 Phenotypic DST

Treatment of TB has undergone significant changes over recent years, with new drugs and regimens being recommended; hence, the definitions for DR-TB have been revised accordingly. The updated definitions are as follows (26):

The availability of follow-on tests to detect additional resistance to anti-TB drugs is becoming increasingly important for making informed decisions on treatment regimens. WHO has recommended four classes: LC-aNAAT for detection of resistance to INH and second-line anti-TB drugs, LPAs, high-complexity reverse hybridization NAATs (HC-rhNAATs) and targeted NGS. A summary of the tests included in the different classes is shown in Table 2.6.

Table 2.6. Comparison of follow-on tests for the detection of drug resistance

2.3.1 Low-complexity manual NAATs

The class of LC-mNAATs is defined in Table 2.5. Only one test met the criteria for the class: the Loopamp™ MTBC detection kit from Eiken Chemical Company in Tokyo, Japan. The test detects MTBC but not drug resistance, and it is useful in decentralized settings with limited laboratory infrastructure. New products that are successfully added to the class by WHO PQ can be found in the WHO list of prequalified in vitro diagnostic products (18).

2.2.1 Low-complexity automated NAATs

In many high TB burden settings, sputum smear microscopy remains the primary diagnostic technique for evaluating individuals who present with the signs and symptoms of TB, or screen positive for TB. However, sputum smear microscopy is an insensitive test, with a limit of detection (LoD) of 5000–10 000 bacilli/mL of sputum (16). Furthermore, sputum smear microscopy cannot distinguish drug-susceptible strains from drug-resistant strains. WHO continues to recommend that NTPs replace microscopy as the initial diagnostic test with WRDs that directly detect MTBC.

This section provides brief descriptions of WHO-recommended technologies for the detection of TB, DR-TB and TB infection. It also summarizes WHO recommendations for such technologies; these recommendations are more thoroughly discussed in the latest versions of the WHO consolidated guidelines on tuberculosis: module 3: diagnosis (5) and the WHO consolidated guidelines on tuberculosis: module 1: prevention (14).

In 2020, WHO changed from product-specific TB testing recommendations to class-based recommendations, with products grouped into classes based on their:

This operational handbook consolidates, for the first time, WHO’s consolidated guidelines on rapid diagnostics for TB detection (6) and tests for TB infection (13). Also, the contents have been revised to support the most recent, evidence-based WHO policy guidance that is described in the 2025 publication, WHO consolidated guidelines on tuberculosis: module 3: diagnosis (5). A high-level summary of the changes made between the third and fourth versions of this handbook is presented in Table 1.2.

The target audience for this handbook includes ministry of health officials, donors, implementing partners, programme managers, laboratory managers, clinicians, civil society and community organizations and other key stakeholders engaged in TB laboratory strengthening or programme support.

This handbook was developed to provide practical guidance for the implementation of WHO policies on recommended TB diagnostic tests and algorithms; it describes:

Over recent decades, considerable effort has gone into building the laboratory, clinical and programmatic capacity to prevent, detect and treat TB infection, TB disease and DR-TB.