In terms of subgroups to be considered for this recommendation, no special considerations are required (e.g. for children, people living with HIV and those with extrapulmonary TB), given that the test is recommended for use on culture isolates.

Implementation considerations Factors to consider when implementing a high complexity hybridization-based NAAT for detection of pyrazinamide resistance are as follows:

• There are specific concerns about the complexity and difficulty of interpretation. The large number of bands makes it difficult to read the result of the high complexity reverse hybridization-based NAAT.
• Local epidemiological data on resistance prevalence should guide local testing algorithms, whereas pretest probability is important for the clinical interpretation of test results.
• The cost of a test varies, depending on the number of samples in a batch, staff time and other parameters requiring a local costing exercise to be performed.
• Low, moderate, and high complexity tests have a successive increase in technical competency needs (qualifications and skills) and staff time, impacting planning and budgeting.
• Availability and timeliness of local support service and maintenance should be considered when selecting a provider.
• Laboratory accreditation and compliance with a robust quality management system (including appropriate quality control) is essential for sustained service excellence and trust.
• Training of both laboratory and clinical staff will ensure effective delivery of services and clinical impact.
• Use of connectivity solutions for communication of results is encouraged, to improve efficiency of service delivery and time to treatment initiation.
• Based on a multinational, population-based study, levels of pyrazinamide resistance varied widely in the surveyed settings (3.0–42.1%). In all settings, pyrazinamide resistance was significantly associated with rifampicin resistance (49).
• Implementation of a high complexity hybridization-based NAAT requires laboratories with the required infrastructure, space and functional sample referral systems.
• Because there are several manual steps involved, well-trained staff are needed to set up assays and maintain instruments. Special training and experience are required for reading of banding patterns on the strip.