Operational Handbooks
1.1 Background
Globally, tuberculosis (TB) continues to be a significant public health problem, with an estimated 10.6 million people developing TB in 2022 and 7.5 million reported as being newly diagnosed (1). The gap between the numbers estimated and reported is large, and it worsened during the coronavirus disease (COVID-19) pandemic (2). However, there has been a major recovery after the 2 years of disruptions related to COVID-19.
References
- Global tuberculosis report 2023. Geneva: World Health Organization; 2023 (https://www.who.int/publications/i/item/9789240083851).
- Impact of the COVID-19 pandemic on TB detection and mortality in 2020. .
4.2.1 Decision pathway for Algorithm 2 – LF-LAM testing to aid in the diagnosis of TB among PLHIV
General considerations for Algorithm 2a and Algorithm 2b
2.2.4 Moderate complexity automated NAATs
The moderate complexity automated NAATs class of tests includes rapid and accurate tests for the detection of pulmonary TB from respiratory samples. Overall pooled sensitivity for TB detection was 93.0% (95% confidence interval [CI]: 90.9–94.7%) and specificity 97.7% (95% CI: 95.6–98.8%) (Tables 3.1–3.4 in Section 3). Moderate complexity automated NAATs are also able to simultaneously detect resistance to both RIF and INH, and are less complex to perform than phenotypic DST and LPAs. After the sample preparation step, the tests are largely automated.
Annex 2. Drug susceptibility testing methods and critical concentrations
Culture-based DST methods for certain anti-tuberculosis (anti-TB) medicines are reliable and reproducible, but these methods are time consuming, and require specific laboratory infrastructure, skilled staff and adherence to quality control.
4.3 Algorithm 3 – DST for second-line drugs for people with RR-TB or MDR-TB
Algorithm 3 is used for further evaluation of people with RR-TB or MDR-TB. In its most recent recommendations (9), WHO stresses the importance of DST before starting the preferred all-oral BDQ-containing MDR-TB regimen, especially for medicines for which mWRDs are available. Two of the key medicines in these regimens are BDQ and FQ. Currently, the only WHO-recommended molecular test to detect mutations associated with BDQ resistance is a targeted NGS test (Deeplex® Myc-TB from GenoScreen).
4.2 Algorithm 2 – LF-LAM testing to aid in the diagnosis of TB among PLHIV
Algorithm 2 is the preferred algorithm for testing to support the diagnosis of TB in PLHIV. It is appropriate for use in settings with a high burden of HIV and for use with individual PLHIV who meet the testing criteria, regardless of the overall HIV burden. The algorithm emphasizes the use of LF-LAM to quickly identify people needing TB treatment; it also emphasizes that all individuals with signs and symptoms of TB should receive a rapid mWRD (Algorithm 1).
4.1.1 Decision pathway for Algorithm 1 – mWRD as the initial diagnostic test for TB
Tests
The mWRDs appropriate for this algorithm include the Xpert MTB/RIF, Xpert MTB/RIF Ultra, Truenat MTB, Truenat MTB Plus and TB-LAMP tests and moderate complexity automated NAATs.
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