Operational Handbooks

The Xpert MTB/RIF assay is a cartridge-based automated test that uses realtime polymerase chain reaction (PCR) on the GeneXpert platform to identify MTBC and mutations associated with RIF resistance directly from sputum specimens in less than 2 hours. WHO recommends using the Xpert MTB/RIF test in the following situations (7):

In many high TB burden settings, sputum-smear microscopy remains the primary diagnostic technique for evaluating individuals presenting with the signs and symptoms of TB. However, sputum-smear microscopy is a relatively insensitive test, with a limit of detection (LoD) of 5000–10 000 bacilli per millilitre of sputum. Furthermore, sputum-smear microscopy cannot distinguish drug-susceptible strains from drug-resistant strains. WHO recommends that TB programmes transition to replacing microscopy as the initial diagnostic test with mWRDs that detect MTBC.

The update of this operational handbook was led by Nazir Ahmed Ismail, Carl-Michael Nathanson, and Alexei Korobitsyn, with support from Cecily Miller and Matteo Zignol, and under the overall direction of Tereza Kasaeva, Director of the World Health Organization (WHO) Global TB Programme (WHO/GTB).

At the central level (Level III), testing that requires highly advanced skills, infrastructure and biosafety precautions is offered. An important expectation at this level is to provide testing to resolve discordant results, troubleshooting, training support to other levels, QA and monitoring, and surveillance.

At the peripheral level (Level I), laboratories offer a range of basic diagnostic tests with the focus on providing initial testing to rapidly detect TB (and RIF resistance):

At the intermediate level (Level II), technologies requiring more sophisticated infrastructure, expertise or biosafety precautions are offered. An important aspect of laboratories at this level is the need for reliable and rapid sample transport networks from peripheral laboratories to the intermediate laboratory, and from the intermediate laboratory to the central laboratory.

Class I BSCs work by drawing unfiltered room air in through a front opening, passing it over the work surface, and then expelling it through an exhaust duct.

Class I BSCs protect workers but do not protect work products (such as specimens or cultures) against contamination because unsterilized room air is drawn over the work surface.

To address specific potential risks, the following biosafety requirements¹⁴ ¹⁵ should be established in a low-risk TB laboratory.

1. Use of bench spaces: The bench used to process specimens for direct sputum-smear microscopy or the Xpert MTB/RIF assay should be separate from areas used to receive specimens and from administrative areas used for paperwork and telephones.

Overall, serious adverse events leading to death or requiring withdrawal of TPT occur rarely. It is nevertheless critical to identify any sign of drug toxicity as soon as possible and to manage it immediately, particularly because people on TPT are usually healthy. Unmanaged drug toxicity may not only harm individuals but can also damage the reputation of a programme and result in widescale suspension of TPT due to loss of public confidence. As in any preventive action, health-care providers must weigh the risks and benefits of TPT for each individual.