Operational Handbooks

Algorithm 1 is the preferred algorithm for testing to support the diagnosis of TB in individuals being evaluated for pulmonary and extrapulmonary TB, and to achieve universal DST. In this algorithm, mWRDs are used as the initial diagnostic test to detect TB, RIF resistance (except if TB-LAMP is used) and – in the case of using moderate complexity automated NAATs – INH resistance (i.e. this algorithm meets the goals of the End TB Strategy for the use of mWRDs and universal DST). If TB-LAMP is used, follow-on testing for RIF resistance is needed.

The target audience for this guide includes ministry of health (MoH) officials, donors, implementing partners, programme managers, laboratory managers, clinicians and other key stakeholders engaged in TB laboratory strengthening or programme support.

This guide was developed to provide practical guidance for the implementation of WHO policies on recommended TB diagnostic tests and algorithms. The guide:

The first-in-class product for low complexity automated NAATs for detection of resistance to INH and second-line anti-TB drugs is the Xpert MTB/XDR Assay (Cepheid, Sunnyvale, USA). This test uses a cartridge designed for the GeneXpert instrument to detect resistance to INH, FQs, ETO and second-line injectable drugs (AMK, kanamycin and capreomycin). However, unlike Xpert MTB/RIF and Xpert MTB/RIF Ultra, which are performed on a GeneXpert instrument that can detect six colours, the new test requires a 10-colour GeneXpert instrument.

Health needs are diverse, and programmes are expected to provide a range of diagnostics to assist health workers in managing patients. The diagnosis of TB often begins with symptom screening, which is not specific to TB, given that cough and fever overlap with COVID-19 and other respiratory infections. Additionally, people with TB may be coinfected with HIV, particularly in sub-Saharan Africa, and services for both diseases are usually provided at the same levels of care.

In selecting a diagnostic test to implement, it is important to consider the characteristics (i.e. risk factors) of the population being served. These characteristics should be derived from population-based studies, if available, and should include the proportion of:

The first-in-class product for this class is the Genoscholar PZA-TB (Nipro, Osaka, Japan) for the detection of resistance to PZA. The Genoscholar PZA-TB test is based on the same principle as the FL-LPA and SL-LPA but requires the use of a large number of hybridization probes to cover the full pncA gene (>700 base pairs [bp]). Reading the hybridization results on the crowded strips with a total of 48 probes requires careful attention to avoid errors. However, it provides faster results than phenotypic DST and is based on molecular detection.

The urine LF-LAM is an immunocapture assay based on the detection of the mycobacterial LAM antigen in urine; it is a potential point-of-care test for certain populations being evaluated for TB. Although the assay lacks sensitivity, it can be used as a fast, bedside, rule-in test for HIV-positive individuals, especially in urgent cases where a rapid TB diagnosis is critical for the person’s survival. The Alere Determine TB LAM Ag is currently the only commercially available urine LF-LAM test endorsed by WHO.