Operational Handbooks

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.

The tables below contain modelled estimates of the performance and outcomes of the 10 screening algorithms described above, when applied to a population of 100,000 people being screened, across three different TB prevalence settings: 0.5%, 1% and 2%. 

1 – Screening with cough

2 – Parallel screening with cough and CXR

3 – Sequential positive serial screening with cough and CXR

4 – Sequential negative serial screening with cough and CXR

5 – Screening with any TB symptom

Since 2011, WHO has recommended that people living with HIV be systematically screened for TB disease at each visit to a health facility. The recommendation is based on the high risk of this group for TB and mortality and a lingering gap in case detection in this population. In 2019, people with HIV were at 18 times greater risk for incident TB than people without HIV and close to one third of deaths from AIDS were due to TB (2). Only 56% of the total estimated number of HIV-positive incident TB cases were detected in 2019 (2).