Remarks

• This recommendation applies to all people with signs and symptoms of the respective formof extrapulmonary TB, including people living with HIV and children.
• Data on the performance of LC-aNAATs when used with urine and blood samples werelimited or inconsistent.
• Where possible, culture may be performed in addition to automated NAAT testing, tomaximize the opportunity for diagnosis and detection of DR-TB.
• The product for which eligible data met the class-based performance criteria for LC-aNAATsfor this recommendation was Xpert MTB/RIF Ultra (Cepheid, Sunnyvale, United States ofAmerica [USA]). Data on Truenat MTB Plus and MTB-RIF Dx were limited and variable andthus were insufficient for evaluation.

Implementation considerations

• Diagnostic products in the low-complexity classes of tests should be prequalified by WHO or approved by another regulator before clinical use.
• Diagnostic test manufacturers, laboratory and programme managers, and policy-makers should be educated on the WHO PQ process for TB IVDs (https://extranet.who.int/prequal/).
• Ensuring sufficient volume and specimen quality is important to obtain accurate results.
• Safe waste disposal of used test consumables needs to be planned in advance to minimize environmental risk.
• Trace positive results on respiratory samples may present false-positive results for TB disease (M. tb. non-viable but DNA detected) in those that are HIV negative or not at risk for HIV, and those with a prior history of TB and an end of treatment within the last 5 years.
• For tests that do not have integrated rifampicin-resistance detection as an all-in-one test, reflex testing for resistance should be performed at the same time for all TB-positive patients to support universal access to DST for rifampicin, at a minimum, and to reduce the risk of loss to follow-up.
• In settings with a very low prevalence of rifampicin resistance7 , i.e. less than 2%, a positive test result for rifampicin resistance may represent a false positive result, and indicate a need for further testing with an alternative method or, at a minimum, repeat testing.
• If rifampicin resistance is detected, further resistance testing for fluoroquinolones and bedaquiline is essential to guide selection of a shorter multidrug-resistant TB or rifampicinresistant TB (MDR/RR-TB) treatment regimen.
• Use of a higher volume of CSF (≥6 mL) with concentration, where possible, is encouraged to increase the sensitivity of LC-aNAATs.